External Review: Report and Self Evaluation - North Carolina State ...

PurposeThis document was prepared to report and assess the accomplishments of theCenter of Comparative Medicine and Translational Research as part of anexternal review. The review occurred August 20-22, 2008 and was conductedby:Joe Kornegay, DVM, PhD, DACVIMHead, CCMTR External Advisory CommitteeProfessor, Department of Pathology and Laboratory Medicine,School of MedicineUniversity of North Carolina, Chapel HillJeffrey Everitt, DVM, DACVP, DACLAMCCMTR External Advisory Committee MemberGlaxo-Smith-KlineResearch Triangle Park, North CarolinaMaria Rapoza, Ph.D.CCMTR External Advisory Committee MemberVice President, Science and Technology Development ProgramNorth Carolina Biotechnology CenterThomas J. Rosol, DVM, PhD, Diplomate ACVPCCMTR External Advisory Committee MemberProfessor, Veterinary BiosciencesCollege of Veterinary MedicineThe Ohio State University1

are not available outside of a veterinary school setting. Moreover, the CCMTRconcentrates on the study of animal disease while the CCGS focuses onhuman disease.In short, while there are several center that may be perceived as having ascientific overlap with the proposed center when examined in detail theoverlap either is nonexistent, or the need for the CCMTR can be justified onthe basis of the focus on veterinary medicine and animal disease, rather thanhuman medicine.The Director and Advisory Committeea) Director. Dr. Jorge Piedrahita as Interim Director of the CCMTR.Dr. Jorge Piedrahita is Professor of Genomics in the Department ofMolecular Biomedical Sciences. He has played a key leadership role in thedevelopment of the CCMTR. In addition to a well funded and internationallyrecognized research program, Dr. Piedrahita has extensive administrativeexperience in research and graduate training programs having been theChair of the Professional Program in Biotechnology, the Associate Directorof the Center for Animal Biotechnology and Genomics, and the co-Directorof the Transgenic Core Facility at Texas A&M University.The responsibilities of the Director of the CCMTR include:1. Provide leadership in short- and long-term planning for the Center andrepresent the CCMTR in college and university meetings, asappropriate.2. Establish collaborative relationships between the CCMTR and otherunits across NCSU, the UNC system, other universities in the area, andthe Research Triangle Park.3. Develop training grants, program project grants and center grants.4. Establish an academic external advisory committee.5. Work with the Comparative Biomedical Sciences (CBS) GraduateProgram, the Clinical Scientist Focus Area (CSFA) in the CVM, andother relevant postdoctoral, graduate, and undergraduate programs toensure that research and educational opportunities at the CCMTR aremaximized.6. Assist with recruiting of exceptional faculty and graduate students.7. Utilize an Advisory Committee (AC) to assist with managing the CCMTR.8. Appoint up to three at-large members to the AC.9. Develop guidelines for pilot project research funding.10. Develop and implement a rigorous review process for evaluating theperformance of research and service cores.b. Advisory Committee (s). The Advisory Committee is composed of onerepresentative from each of the research cores (Allergic Disease, ClinicalGenomics, Emerging and Zoonotic Diseases, Mucosal Pathophysiology, and8

Oncology), three at-large members selected by the Center Director, and theCVM Associate Dean for Research (Ad-hoc member). At present the AdvisoryCommittee members are: Thierry Olivry (Allergic Diseases-DOCS), MatthewBreen (Clinical genomics- MBS), Ed Breitschwerdt (Emerging and ZoonoticDiseases-DOCS), Anthony Blikslager (Mucosal Pathophysiology-DOCS), JonHorowitz (Oncology-MBS), and Marie Davidian (STATS), Greg Gibson(GENE), and Gregg Dean (MBS) as at-large members.Responsibilities of the Advisory Committee include.1. Organizing the members of each of the research cores.2. Review and prioritize CCMTR activities.3. Assist in identifying funding opportunities.4. Assist in developing of grant proposals and other research initiatives.5. Assist with strategic planning of CCMTR activities.6. Attend standing meetings of the CCMTR Advisory Committee everysecond Thursday of each month.7. Attend and participate in any additional meetings as deemed necessary byCCMTR Director.Budget Estimatesa) $100,000/year for five years is available, beginning in FY 2005-2006, toact as "start-up" money for the Center to enhance new research interactionsbetween clinical and non-clinical scientists. This will include an intramuralresearch award program to act as incentive for extramural grantapplications. Preference will be given to projects that are not alreadyfunded, and that include clinical-basic science interactions. Guidelines forfiscal year 2005-2006 awards are attached in Appendix. A maximum of$10,000/year will be applied toward administrative support for the programincluding support of seminar speakers, symposia, travel to represent theCCMTR at funding meetings, web design and maintenance, and officesupplies. The CVM Dean’s Office will provide funds.b) $10,000 first year to sponsor an Inaugural Symposium and Workshop toenhance communication among faculty participating in the Center and todevelop new ideas for collaborations and grant submissions. Symposiumwill be funded in partnership with the CVM Research Office and others.c) Salary support (15%, $21,650 plus benefits) for Dr. Jorge Piedrahita to actas Interim Director of the program until such time as a permanent director isidentified. The CVM Dean’s Office will provide these funds.Space NeedsThe majority of the faculty of the Center is located in the new veterinaryresearch building and the main building of the CVM. As such, the CCMTRdoes not require any additional space or capital equipment beyond a staff9

BYLAWS AND ADMINISTRATIVE GUIDELINESCenter for Comparative Medicine and Translational Research (CCMTR)Article I. Mission StatementThe mission of the CCMTR is to enhance collaborative, interdisciplinaryapproaches for the comparative study of the molecular aspects of animaldiseases. In particular, the center will strive to support interactions betweenclinical and basic research groups within the College of Veterinary Medicineand the university community.An integral part of the center’s mission is to provide clinical and researchopportunities to veterinary students, graduate students, clinical residents, andpostdoctoral fellows. In addition, the center will be a vital component forenhancing and accelerating the development of the Centennial BiomedicalCampus. These goals are relevant to the educational and research mission ofNorth Carolina State University, the UNC system, and the State of NorthCarolina.Article II. Objectives of the CCMTR Research CenterThe aims of the CCMTR are:d) To enhance interactions between clinical and non-clinical faculty at theCVM, and between faculty at the CVM and other colleges at NCSU.e) To build on the veterinary medical expertise and clinical researchopportunities provided by the Veterinary Teaching Hospital.f) To increase access to unique animal resources and create novelcombinations of clinical/basic research expertise.g) To benefit the CCMTR faculty through CCMTR sponsoredmultidisciplinary research funding opportunities and through CCMTRsupported core services.h) To encourage, facilitate, and provide leadership for the continueddevelopment of the Centennial Biomedical Campus.i) To provide additional educational opportunities for veterinary and graduatestudents interested in comparative biomedical research.j) To enhance the competitiveness of the CCMTR faculty for extramuralfunding.k) To increase the visibility of the work carried out by CCMTR members.l) To increase opportunities for obtaining infrastructure and service coresupport from extramural agencies.m) To create opportunities for developing strong interactions with privateindustries.n) To complement existing centers and research programs.Article III. Organizational Structure of the CCMTR Research Center12

a) The Dean of the College of Veterinary Medicine shall be the AdministrativeDesignee (AD) of the CCMTR.b) The Director for the CCMTR will be appointed by the Dean of the College ofVeterinary Medicine in consultation with department heads and members ofthe faculty following a comprehensive search.Article IV. Responsibilities of the CCMTR DirectorThe responsibilities of the Director of the CCMTR include:11. Provide leadership in short- and long-term planning for the center andrepresent the CCMTR in College and University meetings, asappropriate.12. Establish collaborative relationships between the CCMTR and otherunits across NCSU, the UNC system, other universities in the area, andthe Research Triangle Park.13. Develop training grants, program project grants and center grants.14. Establish an academic external advisory committee.15. Work with the Comparative Biomedical Sciences (CBS) graduateprogram, the Clinical Scientist focus area (CSFA) in the CVM, and otherrelevant postdoctoral, graduate, and undergraduate programs to ensurethat research and educational opportunities at the CCMTR aremaximized.16. Assist with recruiting of exceptional faculty and graduate students.17. Utilize an executive committee to assist with managing the CCMTR.18. Appoint up to three at-large members to the executive committee.19. Develop guidelines for pilot project research funding.20. Develop and implement a rigorous review process for evaluating theperformance of research and service cores.Article V. Executive Committee Composition1. The Executive Committee will be composed of one representative fromeach of the research cores, up to three at-large members selected by thecenter director, and the CVM Associate Dean for Research (Ad-hocmember).2. The CCMTR director will chair the EC.3. Representatives for each of the research cores will be selected by themembers of each core by simple majority vote.Article VI. CCMTR Full Membership GuidelinesSuccess of the center will, in large part, depend on assembling faculty withcomplimentary interests and expertise that are willing to work in a highlycollaborative setting. Applications for membership must be evaluated inconsideration of these attributes.The following are the guidelines for Full Membership to the Center:13

1. Research emphasis. There must be a clear fit between the mission of theresearch core and the applicant’s research interest, and/or2. Clinical Expertise. There must be a clear fit between the clinical mission ofeach unit and the applicant’s expertise.3. Record of productivity. Publication record, including clinical cases, will bereviewed.4. Extramural funding record.Full members of the CCMTR are eligible to:a) Vote on matters requiring a vote of the Faculty of the CCMTR.b) Serve on the CCMTR standing committees.c) Chair standing or ad hoc committees of the CCMTR.d) Act as principal investigator (PI) in grants sponsored/funded by theCCMTR.Article VII. Review Guidelines for Full MembersMembership will be reviewed every three years. Renewal will be based onrecord of productivity as it relates to center function and will include thefollowing criteria:1. Evidence of inter- and intra- core collaborations.2. Participation in CCMTR committees.3. Evidence of grant writing efforts with other members of the CCMTR.4. Participation in center activities (seminars, symposia, workshops, annualmeeting).Article VIII. CCMTR Associate Membership GuidelinesTo encourage participation of faculty not meeting the criteria for full membership,an Associate Membership is available. The guidelines for Associate membershipare:1. Research and/or Clinical skills that fit with one or more of the researchcores of the CCMTR.2. Sponsorship by a Full CCMTR member. It is the role of the sponsor tofacilitate the incorporation of the Associate member into the functions ofthe CCMTR and to assist them in becoming a Full CCMTR member.3. Associate members will be reviewed every three years, less if requested,to determine whether guidelines for Full membership have been met.Associate members of the CCMTR are eligible to:a) Serve on standing or ad hoc committees of the CCMTR.b) Act as co-principal investigator on grants sponsored/funded by theCCMTR.c) Participate in all CCMTR-sponsored activities.Article IX. Research Cores of the CCMTRInitially the center will be sub-divided into five areas of focus, as follows:14

1. Allergic Diseases. This core concentrates on the characterizationof spontaneous companion animal allergic diseases.Specific areas of research include:a) Genetic linkage of spontaneous atopic dermatitis and/or foodallergies in specific breeds or experimental allergic lines.b) Mechanisms of allergen sensitization in an experimental modelof allergy.c) Mechanisms of clinical signs development in a canine model offood allergens.d) Mechanisms of IgE-mediated mast cell activation using tissueculture models.e) Relationship of IgE-mediated allergy and renal glomerularlesions in a spontaneous canine model.f) Prevention of spontaneous canine IgE-mediated allergy usinginnate immune system stimulants.g) Testing of novel therapeutics for allergic airway disease.2. Clinical Genomics. This core concentrates on the genetic andepigenetic mechanisms in disease states, and in the identification andanalysis of spontaneous and induced (transgenic) familial andcongenital disorders.Specific areas of research include:a. Cellular genomic approaches for the study and treatment ofcongenital and/or familial disorders.b. Development and implementation of gene expression profilingapproaches to understand normal and abnormal biologicalprocesses.c. Linkage and mapping analysis studies for studying the geneticbasis of inherited disorders.d. Epigenetic and imprinting disregulation effects on abnormal fetaland placental development.e. Development of transgenic animal models of human and animaldisease.f. Development of statistical approaches for the utilization of animalmodels in clinical trials.3. Emerging and Zoonotic Diseases. This core uses an integratedapproach to achieve a better understanding of infectious diseases.Focus areas include molecular pathogenesis, antibiotic resistance,microbial diversity, pathogen detection, therapeutics and vaccines, andthe effects of the environment on infectious disease.Specific areas of research include:15

a) Development of molecular diagnostic tools for bacterial andrickettsial organisms.b) Study of the molecular basis of virulence among bacterialpathogens.c) Improved biosecurity against infectious diseases in productionanimals.d) Advances in molecular epidemiology for the detection andspread of pathogens.e) Study of the basis and spread of antimicrobial resistance inbacteria.f) Vaccine development.4. Mucosal Pathophysiology. This core concentrates on thepathogenetic mechanisms of disease in epithelium lining therespiratory, gastrointestinal, and reproductive tracts.Specific areas of research include:a) Mechanisms of exocytotic secretion of mucus in health anddisease using in vitro and in vivo approaches, including inducedand naturally-occurring animal models.b) Mechanisms of ion and fluid transport across gastrointestinalepithelium in health and disease.c) Mechanisms governing mucosal response to inflammatory andinjurious stimuli, including interactions between multiplemucosal cell types and the extracellular matrix.d) Mechanisms of neutrophil adhesion and activation duringmucosal compromise.e) Mechanisms of airway epithelial injury, repair and developmentof goblet cell hyperplasia and metaplasia using in vitro andinduced in vivo models of inflammatory airway disease.f) Nutritional determinants of enteric disease states as they relateto mucosal injury and repair.5. Oncology. The oncology core concentrates on improving theunderstanding of the pathogenesis and treatment of cancer throughcollaborative research on induced and spontaneous models of cancer.Specific areas of research include:a) Cancer genomics/cytogenetics in lymphosarcoma andosteosarcoma (linkage and mapping analysis, correlation withdisease occurrence and outcome).b) Cell signaling/cell cycle control/differentiation.c) Tumor physiology (effects of intervention on physiologicparameters in tumors).d) Development and testing of novel therapeutics and validation of16

surrogate markers.e) Clinical diagnosis and treatment.6. Biostatistics. The biostatistics core concentrates on thedevelopment of new statistical methodologies to be applied to scientificresearch in the areas of medicine, pharmacology, and public health.Specific areas of research include:a. Development of statistical methods for the design and analysisof clinical trials.b. Bioinformatics and computational biology.c. Statistical genetics including statistical methods to identifysusceptibility genes for complex traits.d. Novel statistical approaches for longitudinal data analysis,survival analysis, and missing data.Article X. Research Cores OrganizationMembers of each research core will elect, by simple majority vote, an individualto represent them (Research Core Leader). Each Core Leader will serve for twoyears and can be re-elected. The elected faculty will be put forward to the centerdirector as members of the CCMTR executive committee.Article XI. Responsibilities of Research Core Leaders1. Facilitate interactions among core participants.2. Assist in developing a strategic plan for the core with short-term and longtermobjectives.3. Assist in developing interactions between research cores.4. Coordinate core responses to program projects, center grants, and otherextramural funding opportunities.5. To prepare, upon request by the center director, reports on research coreactivities for the purpose of promoting core and center activities.Article XII. Research Core ReviewsResearch cores will be reviewed every 5 years by an advisory committeeappointed by the Dean of the CVM upon recommendation of the ExecutiveCommittee of the CCMTR.Criteria for review include:1. Number of collaborative publication between core members (Intra-coreproductivity).2. Number of collaborative publications with members of other cores (Intercoreproductivity).3. Evidence of increase in clinical/non-clinical collaborative research.4. Record of collaborative grant submission and/or funding with othermembers of the core and with members of other cores.5. Participation in the functions of the center including seminars, symposia,17

workshops, etc.Article XIII. Removal and/or Addition of New Research Cores1. Removal of existing research cores. Existing research cores will beevaluated as per article XII. If a research core is deemed to be nonperformingit will be given conditional status for a period of one year atwhich time it will be reviewed again. If the core is still considered to be nonperforming,a recommendation to delete that core from the CCMTR will beforwarded to the EC.2. Request for removal of research core from the center. Members of aresearch core can submit to the center director a request for deletion oftheir core from the center. The request has to be approved by a simplemajority of the voting members of that specific research core.3. Addition of new research cores. At any time a group of investigators canapply for the development of a new research core in the center. Theapplication will be reviewed as per guidelines of article XII. The reviewcommittee has three choices. Reject the application, accept the application,or accept the application conditionally for a one-year period. If therecommendation is for conditional acceptance, a specific detailed list ofareas in need of strengthening will be provided to the applicants. After theone-year conditional period the research area will be re-evaluated. Specialattention will be paid to areas identified as weak in the previous application.Article XIV. Service CoresThe CCMTR will support and encourage the development of service cores thatfacilitate the accomplishment of research core objectives. Service cores shouldbridge the clinical and non-clinical components of the center. Each service coremust appoint a service core director that will be responsible for coordinating coreservices, core growth, and for interacting with the center director and others toobtain support for the core.For example, the CCMTR will seek to develop the following service cores:1. Genetic Resources CoreThe purpose of the core would be to help characterize, bank, and providenaturally occurring and induced (transgenic) animal models to the centermembers. The core should cover the following areas.i. Pathological model evaluation. Clinicians/basic scientists couldcontact the core when a potential model is identified. The core, withassistance from center members, would help characterize and evaluatethe model. If the model were deemed to be of value banking or expansionwould follow.ii. Tissue and gamete banking. This includes freezing of clinicalsamples, or freezing of gametes to protect the line.18

iii. Utilization. Information about the models, both natural andtransgenic, will be made available to center members or theircollaborators. Material will be made available on request.2. Molecular Therapeutics CoreThe purpose of the core would be to develop tools/reagents to the clinicaland research faculty. These could include modified oligonucleotides,siRNA oligos, and viral and non-viral vectors.A core such as this would affect both the clinical and basic work and couldimpact most, if not all, of center members. It is also unique and thus easierto develop a funding support mechanism from extramural sources.Article XV. Service Core ReviewsCCMTR supported service cores will be reviewed every 5 years for continuedsupport. To qualify, service core should:1. Demonstrate evidence of utilization by CCMTR and non-CCMTR faculty.2. Show appropriate use of funds provided.3. Provide evidence of quality service as supported by responses to a facultysurvey.Article XVI. Development of New Service CoresAs new developments and new research needs are identified, members of theCCMTR can request addition of new service cores to the CCMTR. Upon reviewby the EC and approval by the center director, efforts for development andfunding of the new core will be initiated.Article XVII. Meetings1. An annual meeting of the members of the CCMTR shall be held at a timedecided by the center director upon advice of the Executive Committee.2. Special meetings of the members of the CCMTR may be held at the call ofthe center director.3. A regular meeting of the Executive Committee shall be held each fall andspring semester. Other meetings of the Executive Committee may beheld as frequently and for such purposes as are deemed necessary by thecenter director.4. The minutes of each Executive Committee meeting shall be distributed toall members of the CCMTR via e-mail within 10 days after approval by theExecutive Committee.Article XVIII. Standing CommitteesThe members of each standing committee shall be appointed for a two-yearperiod prior to Jan. 1 of each year.19

1. Executive CommitteeThe executive committee, composed as per article V, shall assist thecenter director in managing the CCMTR. The EC will provide key facultyinput into the research directions of the center and will assist with shortandlong-term strategic planning.2. Membership CommitteeThe EC shall serve as the membership committee. It shall screenapplications for membership in the CCMTR. The Committee onMembership shall also review the active status of all members on a threeyearbasis.3. Pilot Project CommitteeThe Committee on Pilot Project Funding shall consist of one member fromeach of the existing research cores and one member from the ExecutiveCommittee that will act as Chair. This committee shall screen grantapplications for pilot funding based on specific guidelines provided to theapplicants and the committee by the EC. Projects recommended forfunding will be submitted to the Executive Committee for approval andimplementation.4. Mentoring CommitteeThe Mentoring Committee will develop and implement a mentoring system toassist faculty in developing extramurally funded projects. This committee willwork with the CVM Research Committee, and the Office of the Associate Dean forResearch to ensure that efforts are not duplicated.5. Ad-hoc CommitteesThe center director shall appoint ad-hoc committees to address specificissues and opportunities that impact the CCMTR. The center director,following discussion with the Executive Committee, will select thecomposition of the committees.Article XIX. AmendmentsProposed amendments to the Bylaws shall be submitted by the Members of theCCMTR to the Executive Committee. The EC shall submit proposedamendments to the full faculty for a vote. A simple majority of members voting bythe stated deadline must approve the requested change for it to become final.20

MembershipAllergic Diseases Research CoreName Position Department CollegeDean, Gregg Professor Molecular Biomedical Sciences CVMHammerberg, Bruce ProfessorPopulation Health &PathobiologyCVMOlivry, Thierry Professor Clinical Sciences CVMVaden, Shelly Professor Clinical Sciences CVMBiostatistics Research CoreName Position Department CollegeBondell, Howard Assistant Professor Statistics CALSDavidian, Marie Professor Statistics CALSGhosh, Sujit Associate Professor Statistics PAMSLi, Lexin Assistant Professor Statistics PAMSLu, Wenbin Assistant Professor Statistics PAMSOsborne, Jason Assistant Professor Statistics PAMSStone, Eric Assistant Professor Statistics PAMSTsiatis, Anastasios (Butch) Professor Statistics PAMSTzeng, Jung-Ying Assistant Professor Statistics PAMSZhang, Daowen Associate Professor Statistics PAMS21

Clinical Genomics Research CoreName Position Department CollegeAtkins, Clarke Professor Clinical Sciences CVMBreen, Matthew Associate Professor Molecular Biomedical Sciences CVMCullen, John Professor Population Health & Pathobiology CVMDeiter, Alex Assistant Professor Chemistry PAMSFarin, Char Professor Animal Science CALSFarin, Peter Associate Professor Population Health & Pathobiology CVMGhashghaie, Troy Assistant Professor Molecular Biomedical Sciences CVMGibson, Greg Professor Genetics CALSGomez, Shawn Assistant ProfessorBioinformatics ComputationalBiologyGilger, Brian Professor Clinical Sciences CVMHauck, Marlene Associate Professor Clinical Sciences CVMLalush, David Assistant Professor Biomedical Engineering ENGLinder, Keith Assistant Professor Population Health & Pathobiology CVMLiu, H. Sunny Assistant Professor Animal Science-Biotechnology CALSEngr/UNC-CHEngr/UNC-CHLoboa, Elizabeth Assistant Professor Biomedical EngineeringMunana, Karen Associate Professor Clinical Sciences CVMOlby, Natasha Assistant Professor Clinical Sciences CVMPetters, Bob Professor Animal Science CALSPiedrahita, Jorge Professor Molecular Biomedical Sciences CVMPetitte, Jim Professor Poultry Sciences CALSRao, BalajiAssistant ProfessorChemical & BiomolecularEngineeringEngineeringSannes, Phil Professor Molecular Biomedical Sciences CVMStoskopf, Michael Professor Clinical Sciences CVMThomas, Rachael Assistant Professor Molecular Biomedical Sciences CVMTonelli, Alan Professor Textile Engineering, Chem & Sci TextilesVaden, Shelly Professor Clinical Sciences CVMYoder, Jeff Assistant Professor Molecular Biomedical Sciences CVM22

Emerging and Zoonotic Diseases Research CoreName Position Department CollegeAgris, PaulProfessorMolecular & StructuralBiochemistryCALSAnderson, Kevin ProfessorPopulation Health &PathobiologyCVMBirkenheuer, Adam Assistant Professor Clinical Sciences CVMBreitschwerdt, Ed Professor Clinical Sciences CVMCullen, JohnProfessorPopulation Health &PathobiologyCVMDean, GreggProfessorMolecular & StructuralBiochemistryCVMGomez, Shawn Assistant ProfessorBioinformatics ComputationalBiologyEngr/UNC-CHGookin, Jody Assistant Professor Molecular Biomedical Sciences CVMGuy, JimProfessorPopulation Health &PathobiologyCVMHoward, Kristina Assistant Professor Molecular Biomedical Sciences CVMKathariou, Sophia Associate Professor Food Sciences CALSKennedy-Stoskopf,SuzanneProfessorPopulation Health &PathobiologyCVMKoci, Matthew Assistant Professor Poultry Science CALSLaster, Scott Professor Microbiology CALSLevine, JayAssociate ProfessorPopulation Health &PathobiologyCVMLevy, MikeProfessorPopulation Health &PathobiologyCVMLewbart, Greg Associate Professor Clinical Sciences CVMLey, DavidProfessorPopulation Health &PathobiologyCVMMariani, Chris Assistant Professor Clinical Sciences CVMMcCaw, Monte Associate ProfessorPopulation Health &PathobiologyCVMNoga, Ed Professor Clinical Sciences CVMNordone, Shila Assistant Professor Molecular Biomedical Sciences CVMOrndorff, Paul ProfessorPopulation Health &PathobiologyCVMPetty, Tim Professor Microbiology CALSRoberts, Malcolm ProfessorPopulation Health &PathobiologyCVMScholle, Frank Assistant Professor Microbiology CALSSherry, Barb Professor Molecular Biomedical Sciences CVMStoskopf, Michael Professor Clinical Sciences CVMThakur, SidAssistant ProfessorPopulation Health &PathobiologyCVMTompkins, Mary ProfessorPopulation Health &PathobiologyCVMYoder, Jeff Assistant Professor Molecular Biomedical Sciences CVM23

Mucosal Pathophysiology Research CoreName Position Department CollegeAdler, Ken Professor Molecular Biomedical Sciences CVMBlikslager, Anthony Associate Professor Clinical Sciences CVMBrody, Arnold Professor Molecular Biomedical Sciences CVMDorman, David Associate Dean Molecular Biomedical Sciences CVMGardner, Sarah Associate Professor Clinical Sciences CVMGilger, Brian Professor Clinical Sciences CVMGookin, Jody Assistant Professor Molecular Biomedical Sciences CVMHawkins, Eleanor Professor Clinical Sciences CVMHoward, Kristina Assistant Professor Molecular Biomedical Sciences CVMJones, Sam Associate Professor Clinical Sciences CVMKoci, Matthew Assistant Professor Poultry Science CALSLascelles, Duncan Assistant Professor Clinical Sciences CVMLaw, MacAssociate ProfessorPopulation Health &PathobiologyCVMMansmann, Richard Professor Clinical Sciences CVMMarks, Steve Associate Professor Clinical Sciences CVMMartin, Linda Assistant Professor Molecular Biomedical Sciences CVMMcGahan, Chris Professor Molecular Biomedical Sciences CVMMichau, Tammy Miller Assistant Professor Clinical Sciences CVMMoeser, AdamAssistant ProfessorPopulation Health &PathobiologyCVMNascone-Yoder, Nanette Assistant Professor Molecular Biomedical Sciences CVMOdle, Jack Professor Animal Science CALSOviedo-Rondon-Edgar Assistant Professor Poultry Science CALSRoberts, Malcolm ProfessorPopulation Health &PathobiologyCVMSannes, Phil Professor Molecular Biomedical Sciences CVM24

Oncology Research CoreName Position Department CollegeAnderson, Ken Professor Poultry Science CALSBarnes, Jill Assistant Professor Molecular Biomedical Sciences CVMBreen, Matthew Associate Professor Molecular Biomedical Sciences CVMBrody, Arnold Professor Molecular Biomedical Sciences CVMFranzen, Stefan Professor Chemistry PAMSHardie, Lizette Professor Clinical Sciences CVMHauck, Marlene Associate Professor Clinical Sciences CVMHaugh, Jason Assistant Professor Chemical Engineering EngineeringHawkridge, Adam Assistant Professor Chemistry PAMSHess, Paul Assistant Professor Clinical Sciences CVMHorowitz, Jon Associate Professor Molecular Biomedical Sciences CVMKim, Yongbaek Assistant Professor Molecular Biomedical Sciences CVMLascelles, Duncan Assistant Professor Clinical Sciences CVMLaw, MacAssociate ProfessorPopulation Health &PathobiologyCVMMariani, Chris Assistant Professor Clinical Sciences CVMMozdziak, Paul Associate Professor Poultry Science CALSMuddiman, David Professor Chemistry PAMSOlby, Natasha Assistant Professor Clinical Sciences CVMPetitte, Jim Professor Poultry Science CALSPiedrahita, Jorge Professor Molecular Biomedical Sciences CVMRodriquez-Puebla,Marcelo Assistant Professor Molecular Biomedical Sciences CVMRose, BobAssistant ProfessorMolecular & StructuralBiochemistryCALSSikes, Michael Assistant Professor Microbiology CALSSmart, Rob Professor Toxicology CALSSuter, Steve Assistant Professor Clinical Sciences CVMThomas, Rachael Assistant ProfessorMoleculare BiomedicalSciencesCVMThrall, Don Professor Molecular Biomedical Sciences CVMTompkins, MaryProfessorPopulation Health &PathobiologyCVMWilliams, Laurel Associate Professor Clinical Sciences CVMCullen, JohnProfessorPopulation Health &PathobiologyCVM25

1The Center for Comparative Medicine and Translational ResearchNews Release – August 6, 2007Researchers Create Chemical ‘Lightmany species,Strategic Development Portfolio planning forone results. medicine.Switches’ to Aid Study of Gene FunctionCCMTR NCSU College of Veterinary Medicine 4700 Hillsborough Street Raleigh, NC 27606 P 919.515.8113 F 919.515.3044 www.ncsu.edu/ccmtr26

Strategic Development PortfolioThe strategic development portfolio was generated as a means of planning andmonitoring progress toward well defined objectives. It was developed by thedirector in conjunction with the executive committee in December 2006. Thecurrent Action Plan is provided as an example of the working roadmap used bythe Director, administrative assistant and executive committee to maintain focuson current initiatives. The Action Plan has been updated six times since theportfolio was compiled.27

CENTER FOR COMPARATIVE MEDICINE AND TRANSLATIONAL RESEARCHSTRATEGIC DEVELOPMENT PORTFOLIODECEMBER 19, 2006I. ForewordThe purpose of this Strategic Development Portfolio is to foster and facilitatesystematic development and innovation in the CCMTR. Traditional 5 yearstrategic plans, while familiar and perhaps comforting only provide the illusion ofsecurity. Technology and economic conditions change too quickly for a detailed5 year plan to be a useful tool for innovation. Strategic initiatives should comefrom CCMTR faculty members. The members are encouraged to proposeinitiatives through Core Leaders, Executive Committee Members, or the Director.Of course, the reality is that time, money, and other resources limit the number ofinitiatives that can be engaged at any one time. Careful consideration of thecost:benefit ratio must be used to select the ‘right’ initiatives. Additionally, wemust consider the cost of not acting on a particular initiative.In section II, the vision for CCMTR is outlined below and simply represents whatwe as faculty see as the benefits of participating in a center in general and theCCMTR specifically. Each enumerated vision item is followed by a briefstatement of the current status of the vision item within the CCMTR. A relevantstrategic initiative follows. The elements of each initiative will be detailed asdescribed in section III.The Strategic Development Portfolio is a dynamic plan that identifies specificinnovations to be accomplished. The timeline and required resources for eachinnovation are specified. This strategic development plan will be reviewed everyregularly to assess progress, add initiatives, and remove completed initiatives.II. Vision1. Encourage new approaches to researcha. Develop novel interdisciplinary/multidisciplinary collaborationsb. Develop translational research teamsCurrent Status: The Center has been successful in bringing investigatorstogether through a variety of mechanisms. Numerous new collaborationshave been launched simply through awareness of expertise, via fortuitousinteractions at workshops and the symposium, through organizedinteractions at the research core level, and importantly, through the pilotgrant program. As we approach the first anniversary of The Center, it isreasonable to anticipate these new collaborations will result in competitivenew grant applications.New Strategic Initiative: Submit 3 new multi-investigator grants28

2. Create funding opportunities througha. New collaborationsb. Pilot study fundsc. Center fundingd. EndowmentsCurrent Status: The pilot grant program is in it’s first year. Results from theprogram will be assessed in May 2007. The pilot grant program willcontinue to be an important mechanism to create new collaborative andfunding opportunities. Strategies to expand the program are ongoing. TheNIH Clinical Translational Science Award (CTSA) that is currently pendingreview would provide a new venue for Center faculty to pursue pilot studyfunding. We have not yet begun to explore opportunities for endowments.New Strategic Initiative: Secure endowments3. Create a structure and environment to:a. Assemble and manage large grants (program projects, center grants,training grants)b. Move IP into the clinicc. Perform clinical trialsd. Interface effectively with industryCurrent Status: With the appointment of a new director and the hiring of a fulltimeadministrative assistant, The Center has the core personnel to assistfaculty in their efforts to accomplish the activities listed above. Two Centerbasedgrants have been submitted, a Clinical Studies Core is ramping upand several Center/corporate interactions have occurred.New Strategic Initiative: Improve technology transfer capability4. Provide cutting edge technology and technical assistance through servicecoresCurrent Status: The first Center-initiated core, the Clinical Studies service corewill be fully functional by spring 2007. Service cores have the potential tosignificantly impact many Center faculty and can leverage extramuralfunding opportunities at the individual and Center levels. Service coresrequire significant resources and therefore must be well conceived,adequately supported, and effectively managed.New Strategic Initiative: Establish 2-3 new service cores5. Train pre- and post-doctoral scientists emphasizing:a. Comparative medicineb. Translational research29

c. Multidisciplinary teamsCurrent Status: New collaborations lead to new training opportunities. Pilotgrants have also been successful to a limited degree in this respect. New,extramurally funded training programs are required.New Strategic Initiative: Establish a Comparative Medicine and TranslationalResearch Training Program6. Provide professional enhancement through:a. Symposiab. Seminarsc. Grant reviewsCurrent Status: The Center has sponsored a variety of programs aimedprimarily at encouraging interaction. This will continue with events such asthe pilot project research in progress presentations to be held in May eachyear. Faculty are encouraged to organize events that are focused onresearch topics or collaborative opportunities. The Center can assist in theorganization and funding of these functions.New Strategic Initiative: Explore level of need and expertise in specific areassuch as stem cell research within The Center as a precursor to recruiting newCenter faculty.7. Provide visibility and recognition of faculty through strategic marketingCurrent Status: The Center has been fairly successful at gaining exposure dueprimarily to the ‘newness’ of the Center. The message and the targeting ofthe message has not been consistent, coordinated or proactive.New Strategic Initiative: Develop and execute marketing strategyIII. Strategic Development InitiativesEach strategic development initiative will undergo an analysis to assess thebackground, current status, risk of taking action, and risk of not taking action.The overall target and objectives will be defined and a cost to benefit ratiodetermined. Finally an action plan will be maintained for all initiatives and will beupdated on a regular basis as elements of the plan are completed (every 3-6months).30

CCMTR Action Items, June-Oct 2008Service CoresCTPReview applicationsConduct interviewsComplete hireFlow coreDetermine fee schedule for LSRII and IVISCCMTR Training ProgramPlace adsJAVMAACVIMACVPEmail trainersEmail CVM facultyConfirm commitment from Vice Chancellor and CVMUpdate websiteCCMTR GrantsInnovations grantPilot projectSend reminder, extend deadline?Send grants to EC for reviewSet review dateNotify applicantsNotify Greta/Barry of awardsMarketing materialsDevelop new multi-purpose print materialsApprove designGenerate contentIdentify printing vendorJuly newsletterCMTRTPInnovations grants updateExternal review overviewResearch spotlightProgram project grant recipientsExternal Advisory Committee/ReviewSchedule outline to committee for approval (first toKornegayOrganize materialsDevelop survey31

Meet with LizetteEventsGI workshopLocationInvited speakersScheduleAdvertisingDAIDS conceptsInvestigate potential opportunities for EZDWebsiteUpdate/revise flow core siteAdd information on becoming a center memberGrantsHire new administrative assistant32

1The Center for Comparative Medicine and Translational ResearchNews Release – August 6, 2007Grant Researchers Programs Create Chemical ‘Lightresearch,full circle.Switches’ to Aid Study of Gene Functionmany species,one medicine.CCMTR NCSU College of Veterinary Medicine 4700 Hillsborough Street Raleigh, NC 27606 P 919.515.8113 F 919.515.3044 www.ncsu.edu/ccmtr33

CCMTR Grant ProgramsProviding seed resources has been a key strategy the center has employed tostimulate new collaborations. To date, the center has three grant mechanismsand will offer two new programs beginning fall 2008. Accountability and outcometracking is built into all grant programs in that recipients of research grants mustpresent results at the annual CCMTR workshop. In addition, any investigatorapplying for Center funding must summarize progress and outcomes from anypreviously received Center funds as part of the application process. Of course,investigators are required to acknowledge the CCMTR as a funding source inany presentations or publications.Pilot GrantsThe goal of this grant program is to enhance translational research and fosterinterdisciplinary collaborations. Request for applications (RFA) occurs in thespring and this program is the focus of the Pilot Grant Workshop held in May. Atthe workshop, recipients of grants from the previous year give a talk describingthe results from their funded project. The workshop provides an opportunity forcenter members to interact and, hopefully, germinate ideas for collaborativeprojects that would be responsive to the RFA. Applications are due in June, arereviewed by the Executive Committee and funds are made available toinvestigators at the beginning of July (the start of the fiscal year). The funds arereverting and must be spent by June 30 of the following year. CCMTR sponsorstwo types of pilot projects.1. Translational research grants to encourage development of new scientificinteractions that involve both a clinical and a basic science component.2. Resource development grants targeted to the development of reagents, toolsand/or animal models that can be used by multiple groups within the CCMTR.Examples are development of a panel of reagents that would be available to alland that can be used by multiple investigators. This could be a panel of34

antibodies, a targeted microarray, a tissue panel, etc. An additional examplewould be funds to maintain a genetic line of animals.Innovation GrantsThe innovation grant program supports proposals that advance the objectives ofthe CCMTR. Specifically, proposals that benefit multiple investigators, encouragebasic/clinical investigator interactions, and/or provide critical resources forsubmission of extramural, multi-investigator proposals are considered responsiveto this RFP. Proposals can be submitted by a research core, a service core,groups of investigators or individual investigators. Funds may be used topurchase equipment, upgrade equipment, develop a new reagent or resource,establish a new service core, expand an existing service core, support aworkshop or invited seminar speaker, or perform critical studies needed for amulti-investigator extramural grant submission.Service Core GrantsThe goal of this grant program is to subsidize member access to CCMTRServices Cores. Applications are continuously accepted and are consideredbased on merit and availability of funds.Travel GrantsTravel has generally not been an allowable budget item for pilot or innovationgrants. However it is of clear benefit to members and the Center for researchsupported by the CCMTR to be presented at national and international meetings.Beginning Fall 2008, Center members can apply for travel funds if they arepresenting an abstract of work that has been supported at least in part by theCCMTR. Applications will be continuously accepted and will be consideredbased on merit and availability of funds.CTSA Grants35

The CCMTR partnered with UNC-Chapel Hill to submit an NIH ClinicalTranslational Science Award (CTSA). The grant was funded in May 2008 andexecution of the program plan is just beginning. Part of the CTSA includedfunding for pilot projects between faculty in the CCMTR and UNC medicalschool. The purpose of the CTSA is to transform how clinical and translationalresearch is conducted, ultimately enabling researchers to provide new treatmentsmore efficiently and quickly to patients. The pilot projects funded by the CTSAwill provide up to $50,000 and could total $200,000 per year for 5 years.SummaryThe tables that follow list investigators, grant titles and funding amounts for thegrant programs for each fiscal year.36

CCMTR FUNDED GRANTS 2006-2007Pilot GrantsPI Title Amount Subtotal Co-PI Co-I Grad StudentsArasu, PremaMBSBlikslager, AnthonyDoCsBreitschwerdt, EdDoCSFarin, CharCALSMuddiman, DonPAMSOdle, JackCALSGibson, GregCALSDeveloping the canine model andreagents to elucidate how parasiticinfection protects against allergic disease 15,000 15,000Development and mechanisms of a novelporcine model of irritable bowel syndrome 15,000 30,000Development and utilization of a serumand urine IL-6 specific canine ELISA forthe clinical detection of the acute phaseresponse in systemic and urinary tractdisease 5,260 35,260Use of cyclodextrins for sustaineddelivery of follicle stimulating hormone insuperovulation protocols for goats andcattle 13,020 48,280Pilot projects in comparative medicineand translation research 15,000 63,280Diet induce transcriptional regulation ofgenes underlying intestinal restitutionexamined in a piglet model 15,000 78,280Development of an illumina genotypingresource for pharmacogenetics of antiepilepticresponses in dogs 15,000 93,280Yoder, JeffMBSNovel immune-type receptors andimmune response in trout 15,000 108,280Breen, MatthewMBSMunana, KarenDoCS Clinical Studies Core 10,000 118,280Olivry,ThierryDoCSPease, TonyMBSDean,GreggMBSTonelli, AlanTEXPiedrahita,JorgeMBSBlikslager,AnthonyDoCSOlby,Natasha,DoCSHinshaw,JeffreyCALSGibson, GregCALSDean, GreggMBSLascelles, DuncanDoCSSwanson, CliffMBSVaden, ShellyDoCSAltier, CraigPHPFarin, PeterPHPBreen, MatthewMBSMunana, KarenDoCSGoldstein, DavidDuke UniversityKennerly, ErinMoeser, AdamWood, MichaelHunt, MarcusFarmer, WilliamMorrison,KatharineIdaghdour,YoussefKennerly, ErinTOTAL AMOUNT AWARDED 2006-2007: $118,28037

CCMTR FUNDED GRANTS 2007-2008Pilot GrantsPI Title Amount Subtotal Co-PI Co-I Grad StudentsDean, Gregg,MBSVaden, Shelly,DoCSBreitschwerdt, EdDoCSShila, Nordone,MBSWood, MichaelGhashghaei, TroyMBSGookin, JodyMBSJones, SamDoCSLevy, MikePHPNordone, ShilaMBSSuter, SteveDoCSYoder, JeffMBSThe development of a canine IL-8ELISA for use with EDTA plasma, urineand cell culture supernatants 8,111 8,111Isolation and characterization of porcinefetal neural stem cell lines and theirapplication for spinal cord repair 15,000 23,111Can supplementation of the periparturientmother enrich fetal intestinalepithelium with bioactive fatty acid andprotect the preterm infant fromnecrotizing enterocolitis? 15,000 38,111Development of a peptide inhibitor ofMARCKS protein to treat inflammation 15,000 53,111In vitro infection of tick cells andmurine/feline erythrocytes withBartonella species 7,500 60,611Identification of conserved Bartonellaspp. Antigens for diagnostic test andvaccine development 15,000 75,611The role of bcl-2 and bax in caninelymphoma 14,925 90,536Assessing the immune response genesas biomarkers for infection 15,000 105,536Olby, NatashaDoCSAdler,KennethMBSBreitschwerdt,EdDoCSTompkins,MaryPHPPiedrahita, JorgeMBSOdle, JackCALSBlikslager,AnthonyDoCSPease, TonyMBSBirkenheuer,AdamDoCSBreitschwerdt,EdDoCSBirkenheuer,AdamDoCSCorrea, MariaPHPJacquet, BenEckert, RachaelNeuder, LauraBilleter, Sarah38

CCMTR FUNDED GRANTS 2007-2008 (cont)Innovations GrantsPI Title Amount Subtotal Co-PI Co-I Grad StudentsYoder, JeffMBSUpgrade of compound microscopeLeica DM5000B and PC workstation 6,612 6,61211 Co-I from 4departmentsDean, GreggMBSExpansion of flow cytometry andcell sorting laboratory service core 31,500 38,112Tompkins,MaryPHPNascone-Yoder,NanetteMBSDetermining the mechanism of action ofa novel small molecule with uniqueteratogenic and melanogenic properties 10,000 48,112Canine B cell lymphomas:Histopathologic, cytologic, flowcytometric, cytogenetic, and molecularcharacterization 10,000 58,112Hauck,MarleneDoCSDeiters, AlexPAMSSuter, StevenDoCS9 Co-I from 3departmentsService Core GrantsPI Title Amount Subtotal Co-PI Co-I Grad StudentsGookin, JodyDoCSBreitschwerdt, EdDoCSSuter, StevenDoCSSuter, StevenDoCSYoder, JeffMBSSeparation of infected and uninfectedbystanderepithelial cells by cell sorting 1,000 1,000Detection of bartonella species infectionamong a cohort of healthy and sickveterinarians and veterinary technicians 3,000 4,000Separation of infected and uninfectedbystanderepithelial cells by cell sorting 2,000 6,000Plasma thymidine kinase as a marker forprognosis and monitoring of caninelymphoma 4,695 10,695Assessing immune response genesas biomarkers for infection 1,350 12,045TOTAL AMOUNT AWARDED 2007-2008: $175,69339

CCMTR FUNDED GRANTS 2008-2009Pilot GrantsPI Title Amount Subtotal Co-PI Co-I Grad StudentsKim, YongbaekPHPIsolation of putative cancer stem cellsusing Hoescht 33452 staining in caninehigh-grade B-cell lymphoma 15,000 15,000Suter,SteveDoCSGilger, BrianDoCSLoboa, ElizabethBMEHawkins, EleanorDoCSEffect of inhibition of Toll-like receptor 2,4, and 9 on inflammation in equine retinalpigmented epithelial cells 19,353 34,353Effects of electrical stimulation onneuronal and glial differentiation of fetalporcine neural stem cells seeded inthree-dimensional Poly-L-Lactic acidscaffolds 21,000 55,353Development of biomarker panel for therapid identification of bacterial infection indogs: TREM-1, PCT and VEGFR-3 8,500 63,853TOTAL AMOUNT AWARDED 2008-2009: $63,853Olby,NatashaDoCSNordone,ShilaMBSMcGahan, ChrisMBSYi, Na YoungDoCSBirkenheuer,AdamDoCSCruse, AshleyDoCSHolowaychuk,MarieDoCSYoder, JeffMBSMcCullen, SethLim, Ji-Hey40

1The Center for Comparative Medicine and Translational Researchmany building species,one teams medicine.EventsNorth Carolina State University College of Veterinary Medicine 4700 Hillsborough Street Raleigh, NC 27606 P 919.515.8113 F 919.515.3044 www.ncsu.edu/ccmtr 41

Workshops, Symposia, and SeminarsMeetings of the Center membership serve as an opportunity to encouragecollaboration, enhance the sense of community and educate. Given that thereare many more opportunities to attend scientific meetings than time allows, theworkshops, symposia, and seminars sponsored by the CCMTR have specificobjectives and have been in limited numbers. CCMTR sponsored events arelisted below and announcements are on the following pages.December 9, 2005 First CCMTR WorkshopOctober 12, 2006 Comparative And Translational Research For ImprovedAnimal And Human HealthMay 4, 2007 Pilot Project Grant WorkshopSeptember 5, 2007 Dr. Chand Khanna: A Comparative Approach To CancerBiology And TherapyApril 11, 2008 Dr. Susie Orton: Translational Medicine in Reverse: Whathuman diagnostics can do for YOUMay 15, 2008 Pilot Project SymposiumDecember 5, 2008 The Intestinal Microbiome: Interactions between host,microbiota, and environment42

Dear CCMM Members,It is a pleasure to announce our first CCMM-sponsored workshop. This being our first one, it is also anextremely important one as it is here that we get to know more about what each of us do and how wecan interact. We have tried to organize the workshop so that we are exposed to some of the programs weare somewhat unfamiliar with but that have tremendous potential for clinical and translational research.Allan Tonelli works in biopolymers and how they can be used in clinical setting, David Muddimanworks in the utilization of mass spectroscopy for clinical diagnosis, Marie Davidian and others in thestatistics group work on developing analytic tools in clinical research, and the Biomedical Engineeringgroup focuses of medical devices. In addition, each of the CCMM cores will provide a brief overview ofwhat each core is doing and can offer.As part of the workshop we will announce the details of the pilot project funds including format,deadlines, funds available, and review process. Thus, this should be an excellent opportunity to listen,think new projects, make connections, and use those connections to write a new pilot project proposal.And while five hours sounds like a lot, take a look a the agenda and you will see that those five hourscan provide you with the foundation of knowledge that will be critical for developing interdisciplinaryapproaches that can have a significant impact in your program.I cannot emphasize how important your participation in this process is. The success of the center is100% dependent on the ability of its members to participate and interact. Otherwise we are just a paperstructure that will accomplish little, if anything. So I strongly encourage you to participate and help ingetting the CCMM started with a positive, productive workshop.You will also be hearing from your core leaders regarding the core presentations. Look forward toseeing you then.We will meet Friday Dec 9th 12 pm- 5 pm in Room 101 (first floor conference room) of the CVMResearch Building.Agenda12:00-1:00 Time for snacks, coffee, drinks (provided), and for informal get together.1:00-1:10 Introduction to CCMM research grants describing the program, aims, deadlines.1:10-1:25. Allan Tonelli Molecular Therapeutics. Development of biopolymers for use in biologicalsystems.1:30-1:50 Allergic Disease. Description of models, tools, approaches.1:50-2:10 Emerging and Infectious Diseases. Description of models, tools, approaches.2:10-2:25 David Muddiman. The Utility of FT-ICR Mass Spectrometry in the Clinical Domain:From Discovery to Targeted Proteomics.2:25-2:50 Break. Time for interaction.2:50-3:10 Biomedical Engineering. Description of models, tools, approaches.3:10-3:30 Clinical Genomics. Description of models, tools, approaches.3:30-3:50 Mucosal Pathophysiology. Description of models, tools, approaches.3:50-4:05 Marie Davidian. Development of analytical tools to enhance clinical research.4:05- 4:25 Oncology. Description of models, tools, approaches.4:25 –5:00 Finger foods/drinks. Time to interact.43

COMPARATIVE AND TRANSLATIONAL RESEARCH FOR IMPROVED ANIMAL AND HUMAN HEALTHOCTOBER 12, 2006The mission of the CCMTR is to enhance collaborative, translational, interdisciplinary approaches for thecomparative study of animal and human diseases. The members of the center recognize that complex issuesaffecting human and animal health are better addressed by interdisciplinary "one medicine" approaches thatcombine both clinical and non-clinical expertise. This includes interactions between different laboratories as wellas interactions with private groups. The ability to provide unique training and expertise, and an environment ofinnovation facilitates the development of novel approaches to diagnose and treat disease.Symposium Goals1. To bring experts in translational and interdisciplinary research to present current research and opinions ontopics of particular interest to CCMTR members and their collaborators.2. To serve as a catalyst for scientific interaction among Center members, speakers and participants throughoutthe Research Triangle Park.3. To inform participants about the nature, opportunities and challenges of translational research. To showcasethe scope and interdisciplinary emphasis on translational research at the CCMTR.Agenda8:00 AM - 8:15 AMWelcome and Introductions8:15 AM - 9:00 AMDavid A. Schwartz, MD, MPH Director, National Institute of Environmental Health Sciences“Environmental Genomics and Human Health”9:00 AM - 9:45 AMDavid Peden, MD, MS Director, Ctr. for Environmental Medicine, Asthma & Lung Biology, UNC"Upregulation of Airway Macrophages and Monocytes by Environmental Agents in Asthma"9:45 AM - 10:30 AMGregory C. Gibson, PhD Distinguished Professor in Genetics, NCSU“Clinical Genomic Application of Microarrays and SNPs”10:30 AM - 10:45 AMBreak10:45 AM – 11:30 AMCorrie Brown, DVM, PhD, DACVPProfessor, College of Veterinary Medicine, University of Georgia“Emerging Diseases-Future Shock is Now”11:30 AM - 12:15 PM Todd Klaenhammer, PhDDistinguished Professor of Food Science & Microbiology, NCSU“Lactic Acid Bacteria and Health: FromGenomics to Clinical Targets”12:15 PM - 1:00 PMDon Thrall, DVM, MS, PhD, DACVR, Professor of Radiology and Radiation Oncology, NCSU“Translational Research Stemming from Clinical Trials in Pets with Cancer: Tumor Heating Can AugmentRadiation Response”Lunch served to all registered participants following Symposium44

Center for Comparative Medicine and Translational ResearchPILOT PROJECT GRANT WORKSHOPMay 4, 2007 2:00 PM – 5:00 PM NC State University ClubDR. FRANZISKA GRIEDERAssociate Director of Comparative MedicineNational Center for Research ResourcesNational Institutes of Health2:00 PM – 3:00 PMRESEARCH-IN-PROGRESS PRESENTATIONS3:00 PM – 3:15 PM PREMA ARASU"Allergies and Parasites: Using the canine model to investigate how infectionattenuates allergic responses"3:15 PM – 3:30 PM JEFF YODER"Examining NITR diversity and response to infection in rainbow trout”3:30 PM – 3:45 PM CHAR FARIN“Use of cyclodextrins for delivery of compounds affecting reproduction”3:45 PM – 4:00 PM JORGE PIEDRAHITA“High throughput method for measuring global DNA methylation in tumorsamples”4:00 PM – 4:15 PM SHEILA JACOBI“Impact of polyunsaturated fatty acids on transcriptions factors involved inregulation COX-2 and repair of ischemic injured porcine ileum”4:15 PM – 4:30 PM ERIN KENNERLY"Pharmacogenetics of response to phenobarbital in canine epilepsy"4:30 PM – 4:45 PM MIKE WOOD"Development of a serum and urine IL-6 specific canine ELISA for the clinicaldetection of the acute phase response in systemic and urinary tract disease"4:45 PM – 5:00 PM ANTHONY BLIKSLAGER“Validation and mechanisms of an animal model of irritable bowel syndrome”45

1The Center for Comparative Medicine and Translational Researchresearch,full circle.research,full circle.many innovation, species,collaborationone medicine.Service Core DevelopmentNorth Carolina State University College of Veterinary Medicine 4700 Hillsborough Street Raleigh, NC 27606 P 919.515.8113 F 919.515.3044 www.ncsu.edu/ccmtr 49

Service Core DevelopmentWithin a center structure, service cores can facilitate research efforts andenhance collaborative opportunities. Without a center-wide grant to support thedevelopment and maintenance of service cores, the CCMTR has employed threestrategies to make unique technology and services available to members.The first strategy is to develop needed cores by building a consortium. Anexample of this is the Clinical Studies Core. The services offered by this core(see below) were previously unavailable but widely viewed as desperatelyneeded. Through a combination of funds from the CCMTR, CVM associate deanof research and two CVM departments (Molecular Biomedical Sciences andClinical Sciences) the initial investment in equipment and technical supportallowed the launch of the core. The core will now be expanded in scope andcapacity by the addition of a new faculty member, the clinical studies coreveterinarian, who will oversee the clinical studies and tissue banking. Thisexpansion is possible through a gift from Novartis Animal Health. Novartis sawthe value in the endeavor and provided $625,000 over five years to facilitate thedevelopment of the core into a self-sustaining entity.A second strategy has been for the CCMTR to ‘adopt’ existing services includingthe Biosafety Level 3 Biocontainment Facility and the Flow Cytometry and CellSorting Laboratory. These two facilities already had developed fee schedulesand billing systems. The advantages to the facilities include increased visibilityand marketing both intramural and extramural. The advantages to the Centerinclude immediate availability of technology to members while creating theopportunity to pursue extramural funding to further reduce the cost of utilizing thefacility.Lastly, the service core grant program essentially allows center members to gainaccess to these resources at a reduced rate. Hopefully this will encourage theinitiation of new collaborations and projects.In January 2008, a survey of membership was performed to assess anticipateduse of existing service cores for the 2008 calendar year, to solicit comments for50

current cores and suggestions for future cores. Responses are shown in thetable below.Service Yes No Unsure No responseFlow Cytometry/Sorting 18 16 9 2BSL3 Lab 2 35 6 2Clinical Trials 9 24 9 3Tissue Banking 8 18 16 3Service Core Grant 5 23 15 2Suggestions for new service cores included a grant assistance core, statisticscore, monoclonal antibody/hybridoma core, and nucleic acidsynthesis/sequencing core.Clinical Studies CoreThe mission of the Clinical Studies Core is to support interactions betweenclinical and basic research groups within North Carolina State University and toexpand collaborative relationships beyond the university with practicingveterinarians, animal owners, and industry partners. The CSC offers supportthrough the following services:• Assistance with all aspects of clinical trials, including publicity and caserecruitment, patient enrollment, patient visits, sample collection andprocessing and patient follow-up• Resources for investigators in the design and implementation of clinicalstudies• Oversight for a repository of veterinary tissue samples to support ongoingand developing studies• A biospecimen procurement service for researchersThe faculty directors of the CSC are Dr. Karen Munana (clinical investigations)and Dr. Matthew Breen (tissue repository). The CSC Steering Committeeprovides oversight. Technical staff includes Ms. Xandi Hamilton and Ms.Kimberly Williams.51

Biosafety Level 3 Biocontainment FacilityBSL3 Biocontainment Facility consists of two large laboratories each with 3 workspaces built around biosafety cabinets. Biosafety Level 3 (BSL-3) agents arethose requiring containment of airborne bacteria, viruses, or toxins, therefore thedesign and administration of the BSL3 Biocontainment Facility follows strictfederal regulations with local oversight provided by the NCSU InstitutionalBiosafety Committee. These and other factors assure the community thatinfectious disease research will not result in occupational hazards for theoccupants of the research building. The BSL3 Biocontainment Facility isavailable for use by the NCSU community. Dr. Ed Breitschwerdt is the facultydirector and Ms. Barb Hegarty manages the facility.Flow Cytometry and Cell Sorting LaboratoryThe NCSU Flow Cytometry and Cell Sorting Laboratory is located on the thirdfloor of the main CVM building and second floor of the CVM Research Building.The laboratory provides instrumentation and assistance for multi-parameter flowcytometric analysis and sorting. It is available for use to all NCSU researchersand to those outside the NCSU community and operates as a by-appointment,fee for service laboratory. Dr. Mary Tompkins is the faculty director and Ms.Janet Dow manages the facility. Ms. Lin Zhang oversees the instrument in theCVM Research Building.52

1The Center for Comparative Medicine and Translational ResearchNews Release – August 6, 2007Researchers Create Chemical ‘LightSwitches’ to Aid Study of Gene Functionmany species,Training planning forone the medicine. future.CCMTR NCSU College of Veterinary Medicine 4700 Hillsborough Street Raleigh, NC 27606 P 919.515.8113 F 919.515.3044 www.ncsu.edu/ccmtr53

TrainingThe CCMTR brings together a unique constellation of faculty researchers and thetheme of comparative medicine and translational research addresses an area ofcritical national need. A major element of the CCMTR mission can be addressedthrough the training of students. Truly multidisciplinary collaborations can oftenbe difficult because of the differences in the language and perspective amongscientists from very different fields such as chemical engineering, mathematicalmodeling, molecular biology, and dermatology. In addition, there are the barriersof time and money. Bringing investigators together in the training of students canhelp bridge the differences and create multidisciplinary teams. The Center isengaged in training several ways as described below.Graduate studentsOne of the criteria considered in reviewing grants for CCMTR funding is whethergraduate students will benefit. The table below lists students who have directlybenefited from CCMTR funding or collaborations initiated through the Center.PI Name Trainee Name Type of Support StatusBlikslager, Anthony Wooten, Jenna Pilot Project PhD candidateBlikslager, Anthony Nighot, Prashant Pilot Project PhD candidateBlikslager, Anthony Cook, Vanessa Pilot Project PhD candidateBlikslager, Anthony Moeser, Adam Pilot Project PhD candidateDean, GreggBreitschwerdt, Ed Wood, Mike CCMTRTP PhD candidateDean, Gregg Tarigo, Jaime CCMTRTP PhD candidateDean, GreggVan Wettere,Arnaud CCMTRTP PhD candidateFranzen, Stefan Kelley, Rich NIH PhD candidateGookin, Jody Wood, Mike Pilot Project PhD candidateFarin, Char Hicks, Jessica Pilot Project MS candidateFarin, CharFarin, Peter Farmer, Will Pilot Project MS candidateFarin, CharFarin, Peter Finely, Lauren Pilot Project MS candidateFarin, Char Shelton, Brian Pilot Project UndergraduateFarin, Char Medlin, Emily Pilot Project UndergraduateFarin, CharFarin, Peter Seay, Sarah Pilot Project UndergraduateHauck, Marlene Snyder, Shelly Pilot Project PhD candidate54

Hauck, Marlene Gilling, Sarah Pilot Project ResidentHauck, Marlene Mahoney, Jennifer Pilot Project ResidentHawkridge, Adam Hawkridge, Adam NIH-NCI K24 Res Asst ProfOlby, Natasha Lim, Ji-Hey Pilot Project Post doctoral fellowPiedrahita, Jorge Tsai, Shengdar NSF Fellowship PhD candidatePiedrahita, Jorge Bischoff, Steve USDA grant PhD candidateSherry, Barb Zurney, Jennifer NIH PhD candidateYoder, Jeff Garner, R. Aaron NIH UndergraduateSummer veterinary scholars research internshipsThis is a very successful program based at the CVM and directed by Drs. SamJones and Jody Gookin. The objective is to encourage the development ofveterinarians as scientists by providing research opportunities for veterinarystudents in faculty laboratories during the summer months. The CCMTR hasfunded five students over the last three years (one in 2006 and two each in 2007and 2008).NIH T32In 2006 a T32 proposal entitled ‘Comparative Medicine and TranslationalResearch Training Program’ (CMTRTP) was submitted to NIH/NCRR with Dr.Gregg Dean as Director and Dr. Sam Jones as Co-Director.While it wasfavorably reviewed it was not funded. A revised proposal was submitted in 2007and was funded beginning August 1, 2008. The abstract from the successfulapplication follows:The National Research Council has documented a dire national need forveterinary specialists trained in biomedical research. Furthermore,veterinary researchers play a key role in comparative and translationalresearch activities since they naturally bridge basic and clinical research.To address this training need, faculty in the Center for ComparativeMedicine and Translational Research (CCMTR) at the College ofVeterinary Medicine, North Carolina State University will establish theComparative Medicine and Translational Research Training Program(CMTRTP). This training program will specifically target individuals withthe DVM degree who have completed specialty training. Trainees willcomplete requirements leading to the PhD degree in laboratories of wellfundedfaculty who have a strong track training record and diverseresearch expertise. Research projects will emphasize comparative andtranslational themes fostered by the CCMTR and trainees will participatein multidisciplinary research efforts. It is envisioned that trainees will55

idge research programs and serve as a nidus for new facultycollaborations. The training program was initiated in Fall 2007 with fundsfor 2 slots committed by North Carolina State University. The program willgrow by two slots each year, reaching a total of 8 slots in year 4. Sixtrainee slots are requested and 2 will be supported from universityresources. Program requirements include: (1) a capstone course oncomparative medicine and translational research; (2) a professionaldevelopment course that will culminate in submission of a K awardproposal; (3) a seminar series on translational research; (4) a course inresearch ethics; and (5) an annual research symposium. Theserequirements are in addition to those associated with a student’s particulargraduate program. This novel training program will build upon the strongcommitment and track record of the NC State CVM to train veterinaryspecialists in research.As a means to jumpstart the program and demonstrate institutional support, theVice Chancellor of Research committed $80,000 and the CVM committed$40,000 per year, for five years. With these intramural funds, two students wereadmitted into the CMTRTP.The first student funded by the NIH T32 wasappointed August 1, 2008. The CMTRTP is an ambitious program involving 22CCMTR faculty and will require the development of several curricular elements.The total award from NIH is $1,446,026 with $600,000 in matching funds fromNC State.NIH T35A T35 proposal was submitted to NIH/NCRR in May 2008 and is pending review.Dr. Sam Jones is the Director on the proposal that involves 27 CCMTR facultyand 6 faculty from other NC State centers.The title of the proposal is‘Interdisciplinary Biomedical Research Training Program‘ and requests a total of$224,751 from NIH with a match of approximately $40,000 from the CVM. Anexcerpt of the abstract follows:The College of Veterinary Medicine (CVM), North Carolina StateUniversity will establish the Interdisciplinary Biomedical Research TrainingProgram (IBRTP) for veterinary students and veterinarians. Trainees willcomplete a 3-month research experience in the laboratories of two facultymembers drawn from seven different disciplines. The 33 facultymembers who have committed to participating in this program have astrong training track record. The seven disciplines chosen are areas of56

strength at North Carolina State University: Clinical Sciences, Cellular andMolecular Biology, Genetics and Genomics, Engineering and Textiles,Statistics and Epidemiology, Biological Chemistry, and Pharmacology,Toxicology, and Nanotechnology. Research projects will emphasize themelding of two disciplines to create a novel approach to a biomedicalresearch problem. Projects combining clinical and basic sciencedisciplines will be given priority. It is envisioned that trainees will bridgeresearch disciplines and serve as a nidus for new faculty collaborations.Trainees will be veterinary students (predoctoral) or graduateveterinarians (postdoctoral). Trainees will be expected to have priorbiomedical research experience. The training program will start in Summer2009 with funds for 2 slots committed by North Carolina State UniversityCVM. Four additional trainee slots are requested in this application forYear 1. The number of trainee slots will grow to a total of 9 in year 3, 6requested in this application and 2 supported by the CVM. Programrequirements include: (1) a weekly seminar series on topics related toresearch ethics and scientific and professional development; (2) a weeklyjournal club discussing interdisciplinary research papers; and (3)participation in an annual CVM research symposium. These requirementsare in addition to those associated with a student’s particular researchtraining experience.57

1The Center for Comparative Medicine and Translational Researchresearch,full circle.research,full circle.many multidisciplinaryspecies,one medicine.CollaborationNorth Carolina State University College of Veterinary Medicine 4700 Hillsborough Street Raleigh, NC 27606 P 919.515.8113 F 919.515.3044 www.ncsu.edu/ccmtr 58

External CollaborationNorth Carolina State University has an outstanding history and record ofcollaboration with industrial partners. Centennial Campus, home to more than130 companies, government agencies and NC State research and academicunits, is remarkable proof of the university’s commitment and success in thisregard.The Centennial Biomedical Campus, anchored by the College ofVeterinary Medicine, extends this model of collaboration into the biomedical field.This has attracted opportunities and interest from a variety of partners. Theinteractions are too numerous to list here but the point is that CCMTR memberscan engage in external collaborations that may facilitate the initiation of researchprojects or help bring innovative ideas to the market.Beyond the willinginstitutional attitude, critical resources are available including flexible researchspace that can be leased by corporate partners and an effective liaison in Ms.Kate Azizi, Director of Corporate and Foundations Relations. Following are just afew external entities that have shown interest in collaborating with the CCMTR.Those indicated by * have resulted in funding for the Center, as a whole, or forindividual members.• Wake County Economic Development• UNC-Chapel Hillo Clinical Translational Science Award*o Center for Gastrointestinal Biology and Diseaseo Lineberger Comprehensive Cancer Center• Golden Pine Ventures• Novartis Animal Health*• Idexx*• Zen-bio• NC Stateo Center for Quantitative Sciences in Biomedicine• RTI International• Hill’s Pet Food• RIKEN*• ALMAC Diagnostics59

Internal CollaborationThe original motivation to establish the CCMTR was to facilitate internalcollaboration. The steering committee realized that there was tremendouspotential for collaborative biomedical research between clinical and basicscientists and between researchers at the CVM and other colleges. The problemwas that this potential was unlikely to be realized without an entity such as theCCMTR that could provide opportunities for interactions among willing faculty.The majority of Center resources have been spent on this objective throughgrants and meetings. Education and training initiatives have also been viewedas an effective way to encourage new collaborations. The director also plays akey role in this regard. As the point person in the Center with knowledge ofmembers research programs, the director is in a position to ‘connect the dots’when an opportunity arises. The frequency of these opportunities has continuedto increase and this is nearly a daily occurrence.Encouraging new interactions is challenging and requires that faculty membersare willing and that there is a reasonable likelihood that there will be a benefit.The advantage of the CCMTR is that members have asked to participate, theyare not obliged by their department or college. The benefit of CCMTR funding forresearch or a trainee is obvious. The benefit from meetings, symposia orworkshops must be carefully considered for such events to be successful.Quantifying the effectiveness of ‘enhancing collaborations’ is difficult becauseclearly some collaboration preceded the existence of the Center and some wouldoccur spontaneously. Four tables follow that help to assess the Center’sactivities. Table 1 lists grants submitted by CCMTR members from September2005 to August 2008 that involved collaborations with other CCMTR members.Those in bold type are definitively the result of Center activities. Those in regulartype, at minimum, demonstrate the interaction among Center members and mayhave been facilitated by the Center. Table 2 lists published papers thatacknowledge the CCMTR. Table 3 shows publications of CCMTR members thatare coauthored with other CCMTR members. The table in the ‘Training’ sectionlists trainees that have been supported, at least in part, by the CCMTR.60

Table 1. Collaborative grants submitted by CCMTR members from September 2005 to August 2008.PI Title Collaborators Status Sponsor Start End TotalAdler, KenAgris, PaulAnderson, KevinBirkenheuer, AdamBirkenheuer, AdamBirkenheuer, AdamBlikslager,AnthonyBreen, MatthewBreen, MatthewBreen, MatthewBreitschwerdt, EdBreitschwerdt, EdBreitschwerdt, EdThe 15th International Colloquium onPulmonary and Airway Fibrosis Brody, Arnold Proposed NIH 9/28/08 11/1/08 $20,000Novel Peptide Intervention Targets aCritical Host-Retrovirus MolecularInteractionA Multidimensional Diagnostic andPrognostic Testing Method to AssessDeiters, AlexFuller, FredHall, Carol Proposed NC Biotech Ctr 7/1/08 6/30/10 $71,039Infectious Disease Farin, Peter Proposed NC Biotech Ctr 7/1/08 6/30/10 $249,984Treatment and Prevention ofLevy, MikeCytauxzoon Felis InfectionsNordone, ShilaALSAMin Domestic CatsBreitschwerdt, Ed Proposed Foundation 7/1/08 6/30/10 $162,500Fort Dodge Animal HealthPostdoctoral Scholar Program Breitschwerdt, Ed AwardedDiscovery of relevant antigens forthe diagnosis and prevention ofcanine babesiosis: an emergingcanine disease in the USA Nordone, Shila AwardedDevelopment and Mechanisms of aNovel Porcine Model of IrritableBowel SyndromeApplication of the 7.5x Canine GenomeAssembly to Generate a 1Mb CytogeneticBAC-map of the Canine Genome Olby, Natasha AwardedCellular Genomics - MolecularCytogenetic Investigation ofCanine Soft Tissue Sarcomas Cullen, John AwardedCellular Genomics - MolecularCytogenetic Investigation ofCanine Soft Tissue Sarcomas Cullen, John AwardedThe development of canine IL-8 ELISA foruse with EDTA plasma urine and cellculture supernatantsPrevalence and Localization of BartonellaSPP. in Vascular Tumors from DogsLinder, KeithMaggi, Ricardo ProposedPotential Infection of Hard Ticks withBartonella Species: an in Vitro andin Vivo Study Levy, Mike ProposedFor DodgeAnimal Health 12/31/06 12/30/09 $135,000NCSU FacultyResearch &ProfessionalDevelop Fund 7/1/07 6/30/08 $8,000Pease, TonyLascelles,DuncanSwanson, Cliff Awarded CCMTR 3/1/06 6/30/07 $15,000Am. KennelClub CanineHealth Found. 1/1/06 12/31/07 $135,959Am. KennelClub CanineHealth Found. 10/1/06 9/30/08 $135,963Am. KennelClub CanineHealth Found. 10/1/06 9/30/08 $135,963Dean, GreggVaden, ShellyNordone, Shila Awarded CCMTR 7/1/07 6/30/08 $8,111Am. KennelClub CanineHealth Found. 9/1/08 8/31/10 $101,185Nat. ResearchFund for TickBorne Diseases 1/1/08 12/31/08 $40,58461

PI Title Collaborators Status Sponsor Start End TotalBreitshwerdt, EdDean, GreggDean, GreggDevelop. & utilization of a serum & urineIL-6 specific canine ELISA for clinicaldetection of the acute phase response insystemic & urinary tract diseaseExpansion of Flow Cytometry and CellDean, GreggVaden, ShellyAltier, Craig Awarded CCMTR 3/1/06 6/30/07 $5,260Sorting Laboratory Service Core Tompkins, Mary Awarded CCMTR 1/1/08 6/30/08 $31,000Development of lactobacillus as novel Klaenhammer, Todd NonfundedHIV vaccine vectorNordone, ShilaNIH 1/1/07 12/31/11 $1,786,736Dean, GreggRecombinant Lactobacillus as an OralMucosal Vaccine Against HIV-1Klaenhammer, ToddNordone, ShilaHoward, Kristina Awarded NIH 2/1/08 1/31/13 $1,856,250Dean, GreggDeiters, AlexDorman, DavidFarin, CharFranzen, StefanGhashghaei, TroyGhashghaei, TroyGookin, JodyGookin, JodyRecombinant Lactobacillus: A MucosalHIV VaccineKlaenhammer, ToddNordone, ShilaHoward, KristinaNonfundedNIH 6/1/06 5/31/11 $1,825,000Switchable Systems for Spatio-TemporalControl of Gene Expression in Zebrafish Yoder, Jeff Awarded NIH 7/1/07 6/30/12 $1,765,603NC State University College of VeterinaryMedicine and Merck-Merial SummerResearch Internship ProgramUse of cylcodestrins for sustaineddelivery of follicle stimlating hormone insuperovulation protocols for goat andcattleNovel Translational Methods:Determiningthe Biodistribution of TargetedTherapeuticsGookin, JodyJones, SamOlson, NeilAwardedMerckCompanyFoundation 1/1/08 12/31/11 $68,173Tonelli, AlanFarin, Peter Awarded CCMTR 3/1/06 6/30/07 $13,020Dean, GreggHauck, MarleneLommel, Steven Proposed NC Biotech Ctr 8/1/08 7/31/10 $239,426Isolation, characterization and utilizationof procine neural stem cellsOlby, NatashaPiedrahita, Jorge Awarded CCMTR 7/1/07 6/30/08 $15,000Transcriptional Regulation of Aging in theDeveloping Adult Stem Cell Niche Horowitz, Jon Proposed NIH 1/1/08 12/31/12 $1,841,739Can supplementation of theperi-parturient mother enrich fetalintestinal epithelium with bioactive fattyacids and protect the preterm infant fromnecrotizing enterocolitis?NC State University College of VeterinaryMedicine and Merck-Merial SummerResearch Internship ProgramOdle, JackBlikslager,AnthonyPease, Tony Awarded CCMTR 7/1/07 6/30/08 $15,000Dorman, DavidJones, SamOlson, NeilAwardedMerckCompanyFoundation 1/1/08 12/31/11 $68,17362

PI Title Collaborators Status Sponsor Start End TotalGookin, JodyMechanisms of t.foetuspathogenicity and novelsites for pharmacological controlBirkenheuer, AdamNielsen, Dahlia ProposedMorris AnimalFoundation 1/1/09 12/31/11 $135,217Gookin, JodyGene Expression Profiling of IntestinalEpithelial Cell Responses toCryptosporidium Parvum Infectionin Vitro and in Vivo.Nielsen, DahliaPiedrahita, JorgeNonfundedNIH 7/1/07 6/30/09 $401,500Gookin, JodyIs Tinidazole an Effective Treatment forFeline Tritrichomonas Foetus Infection?Levy, MichaelPapich, MarkAwardedPresuttiLaboratories 8/1/05 7/31/06 $17,947Hammerberg, BruceComparison of the Cutaneous andSystemic Immune Response toEpicutaneous Applications ofProteolytically Active or InactiveDer f 1 in Allergy-PredisposedPucheu-Haston,CherieOlivry, ThierryJackson, HilaryAwardedAmericanAcademy ofVeterinaryDermatology 4/1/06 3/31/07 $6,370Hammerberg, BruceHammerberg,BruceComparison of the Cutaneous andSystemic Immune Response toEpicutaneous Applications ofProteolytically Active or InactiveDer f 1 in Allergy-Predisposed DogsGenetic High-Risk Dog Model for FoodAllergyOlivry, ThierryJackson, HilaryPucheu-Haston,CherieDean, GreggOlivry, ThierryKlaenhammer,ToddAwardedAmericanAcademy ofVeterinaryDermatology 4/1/06 3/31/07 $5,000NonfundedNIH 8/1/08 7/31/10 $408,375Hauck, MarleneApplication of a Human 10,000 GeneMicroarray to Evaluate Gene Expression inFeline Tissues - PilotGillings, SarahLaw, JerryAwardedMorris AnimalFoundation 9/1/06 7/31/08 $8,100Haugh, JasonEFRI-CBE Preliminary Proposal:Molecular Control of Intracellular Signalingto Guide Stem Cell FateRao, BalajiGenzer, JanNonfundedNationalScienceFoundation 1/1/08 12/31/11 $2,000,000Hawkins, EleanorHawkridge, AdamTheophylline is an EffectiveTreatment For Dogs WithChronic BronchitisComparative Proteomics Applied tothe Avian Model of Ovarian CancerBirkenheuer, AdamPease,AnthonyMuddiman, DavidHorowitz, JonMozdziak, PaulAnderson, KenPetitte, JamesNielsen, DahliaNonfundedNonfundedMorris AnimalFoundation 9/1/07 8/31/09 $50,706National CancerInstitute 2/1/08 1/31/13 $654,07963

PI Title Collaborators Status Sponsor Start End TotalHawkridge, AdamHorowitz, JonHorowitz, JonHorowitz, JonHoward, KristinaHoward, KristinaHoward, KristinaJones, SamJones, SamJones, SamComparative Proteomics Applied to theAvian Model of Ovarian CancerGeneration and Characterization ofSp-transgenic MiceNikon AZ100 Macro/Micro ZoomMicroscopeSp2: A Regulator of Development andTumorigenesisImmunologic Correlates of VaccineProtection: mMucosal Versus SystemicMuddiman, DavidHorowitz, JonMozdziak, PaulAnderson,KenPetitte, JamesNielsen,Dahlia Awarded NIH 9/1/07 8/31/12 $716,850Cullen, JohnSmart, RobNonfundedNCSU FacultyResearch &ProfessionalDevelop. Fund 7/1/06 6/30/07 $20,000McGahan,MaryRodriguez-Puebla,MarceloPiedrahita, JorgeNascone-Yoder,NanetteYoder, Jeff Awarded NIH 4/1/08 3/31/09 $107,425Smart, RobMuddiman, DavidCullen, JohnRodriguez-Puebla,MarceloWofinger,RussellLinder, Keith Proposed NIH 4/1/09 3/31/14 $1,799,365NonfundedDean, GreggNIH 7/1/06 6/30/08 $438,000Investigating AIDS-Related MalignanciesEtiology & Pathogenesis Via FIV/CatModel Suter, Steve Proposed NIH 4/1/08 3/31/10 $408,375Mechanisms of Protection VersusTolerance Induced by an oral Mucosal FIVVaccine Dean, Gregg Proposed NIH 2/1/08 1/31/10 $408,375MARCKS Protein Regulation of Integrin Adler, KenFunction in Neutrophi MigrationGhashghaei, Troy Proposed Am Heart Assoc 7/30/08 6/30/10 $132,000Development of peptide inhibitor ofMARCKS proteint to treat inflammation Adler, Ken Awarded CCMTR 7/1/07 6/30/08 $15,000Role of the Cytoskeletal ProteinMARCKS in Neutrophil MigrationAdler, KenNotFunded NCSU Fac Res 7/1/06 6/30/07 $20,000Jones, SamPrevalence of Bartonella HenselaeInfection in North Carolina Horses Breitschwerdt, Ed ProposedNC HorseCouncil 8/1/08 7/31/09 $6,00064

PI Title Collaborators Status Sponsor Start End TotalKim, YongbaekIsolation of putative cancer stem cellsusing Hoescht 33452 staining in caninehigh grade B cell lymphoma Suter, Steve Funded CCMTR 7/1/08 6/30/09 $15,000Kim, YongbaekThe IGF-1R Pathway in Cancer Stem CellsIsolated by Side Population Assay in HumanMalignant MesotheliomaBrody, ArnoldRodriguez-Puebla,MarceloNotFunded NIH 5/1/08 4/30/10 $408,375Kim, YongbaekThe role of Phosphoinositide-3 kinasesignaling in the maintenance of sidepopulation cells of human malignantmesotheliomas Brody, Arnold ProposedUS Dept. ofDefense 7/1/09 6/30/12 $1,298,351Koci, MatthewLascelles, DuncanTurkey Astrovirus Type-2 Model ofInfant Diarrhea Blikslager, Anthony AwardedEvaluation of Client Specific OutcomeMeasures as a Measure of Pain Relief inFeline OsteoarthritisHansen, BernardHardie, ElizabethMarcellin-Little,DenisNCSU FacultyResearch &ProfessionalDevelop. Fund 7/1/06 6/30/07 $14,274Morris AnimalFoundation 7/1/06 6/30/08 $11,138Lascelles, DuncanLascelles, DuncanLaster, ScottLaster, ScottLevine, JayLevy, MikeMariani, ChristopherDevelopment and Mechanisms of aNovel Porcine Model of IrritableBowel SyndromeExpression and Activity of Cox-1 And 2in Joint Tissues and the Spinal Cord inDogs with Naturally OccurringOsteoarthritisRole of Prostaglandins in ImmuneResponses to PoxvirusesThe Effects of Em-1421 on InfluenzaReplication, Influenza-induced Apoptosisand Influenza-induced InflammationBlikslager, AnthonyPease, AnthonySwanson, Cliff Proposed NIH 10/1/06 9/30/11 $1,836,500Blikslager, AnthonyJones, SamPetty, I. TimScholle, FrankPetty, IanNonfundedAwardedSchering-PloughAnimal Health 7/1/06 7/1/07 $65,104NonfundedNIH 9/1/07 8/31/09 $371,250AwardedEffects of Polychlorinated Biphenyls onNon-Native and Native Freshwater Bivalves Law, Jerry AwardedArtificial Feeding of Two Hard Tick SpeciesWith Canine Blood Infected With BartonellaVinsonii Subsp. Berkhoffii (AKC Acorn GrantFor Sarah Billeter) Breitschwerdt, Ed ProposedBreen, MatthewMatrix Metalloproteinase-2 and -9 and Olby, NatashaCathepsin-B in Canine Meningiomas Linder, Keith ProposedErimosPharmaceutical 1/30/06 4/30/08 $368,090NektonResearch LLC(Prime-USDept. Defense) 3/15/07 9/30/07 $91,535AmericanKennelClub CanineHealth Found. 3/1/08 2/28/09 $10,260Morris AnimalFoundation 7/1/09 6/30/11 $52,38065

PI Title Collaborators Status Sponsor Start End TotalMozdziak, Paul Transgenic Vertebrates Petitte, James AwardedBob ClarkCaptive BredReptile 7/15/08 11/30/09 $149,500Mozdziak, PaulA Method for Inter- and Intra-SpeciesGamete Production Petitte, James Awarded Merial Limited 8/1/07 2/1/08 $44,550Mozdziak, PaulMuddiman, DavidMuddiman, DavidFunctional Role of the Peptide TransporterPepT1 in Chickens Petitte, James ProposedSp2: A Regulator of Development andTumorigenesisSp2: A Regulator of Development andTumorigenesisVAPolytechnicInstitute andState University 12/1/08 12/30/11 $900,002Horowitz, Jon*Smart, RobCullen, JohnRodriguez-Puebla,MarceloWofinger,RussellLinder, Keith Proposed NIH 4/1/09 3/31/14 $1,799,365Horowitz, Jon*Smart, RobCullen, JohnRodriguez-Puebla,MarceloWofinger,RussellLinder, Keith Proposed NIH 4/1/09 3/31/14 $1,799,365Muddiman, DavidPilot projecs for comparative medicineand translational researchPiedrahita, JorgeBreen, Matthew Awarded CCMTR 3/1/06 6/30/07 $15,000Muddiman, David Cardiac Peptides in Cardiorenal Protection Hawkridge, Adam AwardedMayoFoundation-NIH 5/1/07 4/30/08 $60,923Muddiman, David Cardiac Peptides in Cardiorenal Protection Hawkridge, Adam AwardedMayoFoundation-NIH 4/1/06 3/31/11 $305,867Muddiman, DavidMuddiman, DavidNascone-Yoder,NanetteIntegrated Analytical Technologies ForQuantitative Targeted Clinical ProteomicsHawkridge, AdamDevelopment and Implementation ofQuantitative LC-MS/MS Strategies forMeasuring Endogenous Levels of Human C-reactive Protein in Human Plasma Hawkridge, Adam AwardedDevelopment of a Chemical GeneticApproach to Xenopus MorphogenesisDeiters, AlexNonfundedNIH 7/1/07 6/30/12 $1,779,997Philip MorrisUSA Inc. 3/1/07 2/29/08 $173,718NonfundedNIH 12/1/07 11/30/12 $1,837,357Nasone-Yoder,NanetteDetermining the mechanisim of action ofa novel small molecule with uniqueteratogenic and melanogenic propertiesDeiters, AlexHauck, Marlene Awarded CCMTR 1/1/08 6/30/08 $10,00066

PI Title Collaborators Status Sponsor Start End TotalNordone, ShilaIdentification of conserved Bartonellaspp. Antigens for diagnostic test andvaccine developmentBirkenheuer,AdamBreitschwerdt, Ed Awarded CCMTR 7/1/07 6/30/08 $15,000Nordone, ShilaNordone, ShilaNordone, ShilaNordone, ShilaOdle, JackOdle, JackOlby, NatashaOlby, NatashaOlby, NatashaOlby, NatashaEvaluation of TREM-1 as a SpecificBiological Marker for Sepsis in DogsRole of TREM-2 in HIV-1-Induced InnateImmune System DefectsToll-like Receptor-mediated Dendritic CellResponses During HIVBirkenheuer,AdamYoder, JeffDean, GreggDean, GreggAwardedImpact of TLR Function on RegulatoryT Cell-Mediated Suppression DuringHIV/FIV Infection Dean, Gregg AwardedDiet induce transcriptional regulation ofgenes underlying intestinal resitutionexamined in a piglet modelNational Needs Fellowship Program inFood Animal Functional GenomicsGene Discovery in Hereditary CerebellarAbiotrophy of Scottish TerriersIdentification of Mutations CausingHerediatry Cerebellar Cortical Degenerationin American StaffordshireTerriers and Old English SheepdogsMethylprednisolone Sodium Succinate andPolyethylene Glycol in Canine Spinal CordInjury: a Multicenter, Placebo-ControlledTrialMethylprednisolone Sodium Succinateand Polyethylene Glycol in Canine SpinalCord InjuryMorris AnimalFoundation 9/1/08 8/31/11 $224,078NonfundedNIH 6/1/07 5/31/09 $401,500NonfundedNIH 12/1/06 12/1/08 $401,500UNC Center forAIDS Research 6/1/07 5/31/08 $15,000Blikslager,Anthony Awarded CCMTR 3/1/06 6/30/07 $15,000Ashwell,MelissazCassady,JosephKoci, MatthewLiu, Hsiao-ChingMozdziak, PaulPetitte, JamesBird, DavidAshwell,ChristopherSwanson, RebeccaBreen, MatthewNielsen, DahliaBreen, MatthewNielsen, DahliaDavidian, MarieMariani, ChristopherMunana, KarenDavidian, MarieMunana, KarenNonfundedAwardedAwardedProposedAwardedUS Dept. ofAgriculture 7/1/09 6/30/14 $234,000Am. KennelClub CanineHealth Found. 10/1/07 9/30/09 $54,810AmericanKennelClub CanineHealth Found. 10/1/07 9/30/08 $64,800AmericanKennelClub CanineHealth Found. 10/1/07 9/30/09 $69,120Morris AnimalFoundation 7/1/07 6/30/09 $79,92067

PI Title Collaborators Status Sponsor Start End TotalOlby, NatashaAxonal Tracing byManganese Enhanced Magnetic ResonanceImaging:a Pilot Study in Dogs(multidisciplinary FRPD)Lalush, DavidPease, Anthony AwardedNCSU FacultyResearch &ProfessionalDevelop. Fund 7/1/07 6/30/08 $20,000Olby, NatashaGene Discovery in a Canine Model ofHereditary AtaxiaBreen, MatthewNielsen, DahliaNonfundedNIH 1/1/06 12/31/07 $401,500Olby, NatashaOlivry, ThierryOrndorff, PaulOviedo, EdgarOviedo, EdgarPetters, RobertPetters, RobertPetters, RobertPetty, I. TimPiedrahita, JorgePiedrahita, JorgePiedrahita, JorgeGene linkage in atopic dermatitis of WestHighland White Terriers Olivry, Thierry AwardedIntegrated Analysis of Factors InfluencingLameness in PoultryIntegrated Analysis of Factors InfluencingSpiral Femoral Fractures in TomsMente, PeterLascelles,DuncanLiu, Hsiao-ChingFerket, PeterFerket, PeterLiu, Hsiao-ChingLascelles,DuncanMente, PeterWestie Found.of America $12,500RIKENResearch Ctrfor Allergy andImmunology 1/1/07 12/31/08 $260,555NCSU FacultyResearch &ProfessionalDevelop.Fund 7/1/06 6/30/07 $20,000NCSU FacultyResearch &ProfessionalDevelop.Fund 7/1/06 6/30/07 $14,970United StatesPoultry & EggAssoc. 8/6/07 7/31/08 $29,995A pilot study of the efficacy of sublingualimmunotherapy in a canine model of allergy Hammerberg, Bruce AwardedHavell, EdBarnes, HaroldDevelopment of Bordetella Avium as a Live Guy, James NonfundedAttenuated Vaccine Platform in Poultry Christensen,VernNonfundedAwardedPiedrahita, JorgePetters, RobertDevelopment of a Swine Model of Marfan Gilger, BrianSyndromePease, Anthony Awarded NIH 7/1/07 6/30/09 $401,500CTRP-Transgenics and Knockouts asModels of Macular Degeneration Piedrahita, Jorge Awarded NIH 7/1/07 6/30/09 $414,184Transcript Profiles of Sow and GiltNonfundedUS Dept. ofOocytesFarin, CharlotteAgriculture 8/1/06 12/31/08 $349,611Role of Prostaglandins in ImmuneNonfundedResponses to PoxvirusesLaster, ScottNIH 9/1/07 8/31/09 $371,250Development of a Large Animal Model ofNonfundedNational MarfanMarfan SyndromePetters, RobertFoundation 1/1/07 12/31/07$50,000A Porcine Model of Skin CancerDevelopment of a Swine Model of MarfanSyndromeThrall, DonBreen, MatthewPetters, Robert Proposed NIH 12/1/07 11/30/12 $1,879,400Petters, RobertGilger, BrianPease, Anthony Awarded NIH 7/1/07 6/30/09 $401,50068

PI Title Collaborators Status Sponsor Start End TotalRodriguez-Puebla,MarceloSuter, SteveSuter, SteveThakur, SiddharthaThakur, SiddharthaThomas, RachaelTompkins, MaryNikon AZ100 Macro/Micro ZoomMicroscopeCanine B cell Lymphomas:Histopahtologic, Cytologic, FlowCytometric, Cytogenetic, and MolecularCharacterizationHorowitz, JonMcGahan, MaryPiedrahita, JorgeNascone-Yoder,NanetteYoder, Jeff Awarded NIH 4/1/08 3/31/09 $107,425Breen, MatthewTompkins, MaryNeel, JenniferMatthew, KyleLascelles,DuncanCullen, JohnRustlander, DaveValli, TedVernaue, William Awarded CCMTR 1/1/08 6/30/08 $10,000The role of bcl-2 and bax in caninelymphoma Tompkins, Mary Awarded CCMTR 7/1/07 6/30/08 $14,925Molecular Epidemiology of ViableCampylobacter Jejuni in Post-Harvest Cattle Anderson, Kevin Proposed Ohio State Univ 7/1/08 6/30/11 $47,801Bridging Molecular Biology,Epidemiology & Microbiology to EnhanceFood Safety TrainingJaykus, Lee-AnnLevine, JayNelson, StacyProposedMolecular Cytogenetic Evaluation ofFeline Fibrosarcoma by Array-CGH:A Diagnostic Tool? Breen, Matthew AwardedTreg Cells Maintain Balance BetweenImmunity & Immunopathology in FIVInfectionDean, GreggUS Dept. ofAgriculture 10/1/08 9/30/11 $243,795Morris AnimalFoundation 10/1/06 9/30/08 $103,152NonfundedNIH 4/1/06 3/31/11 $1,460,000Tzeng, Jung-YingWilliams, LaurelWilliams, LaurelGenome-wide Haplotype AssociationAnalysis in Mental DisordersAntiangiogenic (metronomic)Chemotherapy in Canine Osteosarcoma Hess, Paul ProposedMultidrug Resistance and Response toShort Duration Chemotherapy Followed ByHalf-Body Radiation Therapy For CanineLymphomaBondell, HowardZhang, Daowen Proposed NIH 8/16/08 8/15/11 $888,216Am. KennelClub CanineHealth Found. 3/1/08 2/28/10 $50,000Hauck, MarleneHess, PaulLinder, KeithPruitt, AmySuter, SteveThrall, DonNonfundedAmericanKennelClub CanineHealth Found. 10/1/06 9/30/08 $100,73069

PI Title Collaborators Status Sponsor Start End TotalWilliams, LaurelWilliams, LaurelWilliams, LaurelYoder, JeffYoder, JeffThe Impact of Anti-Angiogenic(Metronomic) Chemotherapy on Pro- andAnti-Angiogenic Factors and Outcome inCanine Osteosarcoma Hess, Paul ProposedThe Impact of Metronomic Therapy onRegulatory T Cells, Angiogenesis, andSurvival in Canine Osteosarcoma Hess, Paul ProposedCardiac Changes and Left VentricularSystolic Function in Dogs with Lymphomaas Compared to Unaffected Breed-, Age-,andGender-Matched ControlsAssessing the immune response genesas biomarkers for infectionUpgrade of compound microscope LeicaDM5000B and PC workstationA Small Molecule Approach to GeneRegulation in Zebrafish Deiters, Alex AwardedAmericanKennelClub CanineHealth Found. 9/1/08 8/31/10 $85,470Morris AnimalFoundation 7/1/08 6/30/10 $107,680Atkins, ClarkeKeene, Bru ceDeFrancesco,Teresa Awarded Waltham Found 7/1/07 6/30/09 $15,000Birkenheuer,AdamCorrea, Maria Awarded CCMTR 7/1/07 6/30/08 $15,000Breen, MatthewDean, GreggDeiters, AlexGadsby, JohnHauck, MarleneHorowitz, JonMcGahan, ChrisNascone-Yoder,NanettePiedrahita, JorgeSherry, BarbSuter, Steve Awarded CCMTR 1/1/08 6/30/08 $6,612NCSU FacultyResearch &ProfessionalDevelop. Fund 7/1/06 6/30/07 $20,000Yoder, JeffTotal AmountRequested $41,403,75270

Table 2. Publications acknowledging the CCMTR.1. Breitschwerdt EB, Maggi RG, Nicholson WL, Cherry NA, Woods CW. Bartonella spp. bacteremia in patients withneurological and neuro-cognitive dysfunction. J Clin Microbiol. 2008 Jul 16. [Epub ahead of print]2. Olivry T, Mueller R, Nuttall T, Favrot C, Prelaud P, International Task Force on CanineAtopic Dermatitis. Determination of CADESI-03 thresholds for increasing severity levels of canine atopicdermatitis. Vet Dermatol. 2008 Jun;19(3):115-93. Breen M. Canine cytogenetics--from band to basepair. Cytogenet Genome Res. 2008;120(1-2):50-60. Epub 2008 Apr 30.4. Cadenas MB, Bradley J, Maggi RG, Takear M, Hegarty BC, Breitschwerdt EB. Molecularcharacterization of Bartonella vinsonii subsp. berkhoffii genotype III. J Clin Microbiol. 2008 May;46(5):1858-60.Epub 2008 Mar 26.5. Jones SL, Maggi R, Shuler J, Alward A, Breitschwerdt EB. Detection of Bartonella henselae in the Blood of 2Adult Horses. J Vet Intern Med. 2008 Mar-Apr;22(2):495-86. Yoder JA, Cannon JP, Litman RT, Murphy C, Freeman JL, Litman GW. Evidence for a transposition event in asecond NITR gene cluster in zebrafish. Immunogenetics. 2008 May;60(5):257-65.7. Duncan AW, Marr HS, Birkenheuer AJ, Maggie RG, Williams LE, Correa MT, Breitschwerdt EB. Bartonella DNAin the blood and lymph nodes of Golden Retrievers with lymphoma and in healthy controls. Vet Intern Med. 2008Jan-Feb;22(1):89-958. Billeter SA, Miller MK, Breitschwerdt EB, Levy MG. Detection of two Bartonella tamiae-like sequences inAmblyomma americanum (Acari: Ixodidae) using 16S-23S intergenic spacer region-specific primers.J MedEntomol. 2008 Jan;45(1):176-99. Kidd L, Maggi R, Diniz PP, Hegarty B, Tucker M, Breitschwerdt E. Evaluation of conventional and real-time PCRassays for detection and differentiation of Spotted Fever Group Rickettsia in dog blood. Vet Microbiol. 2008 Jun22;129(3-4):294-303.10. Nordone SK, Ignacio GA, Su L, Sempowski GD, Golenbock DT, Li L, Dean GA. Failure of TLR4-driven NF-kappaB activation to stimulate virus replication in models of HIV type 1 activation. AIDS Res Hum Retroviruses. 2007Nov;23(11):1387-9511. Macias E, de Marval PL, Senderowicz A, Cullen J, Rodriguez-Puebla ML. Expression of CDK4 or CDK2 inmouse oral cavity is retained in adult pituitary with distinct effects on tumorigenesis. Cancer Res. 2008 Jan1;68(1):162-7112. de Paiva Diniz PP, Schwartz DS, de Morais HS, Breitschwerdt EB. Surveillance for zoonotic vector-borneinfections using sick dogs from southeastern Brazil. Vector Borne Zoonotic Dis. 2007 Winter;7(4):689-9713. Olivry T, Kurata K, Paps JS, Masuda K. A blinded randomized controlled trial evaluating the usefulness of anovel diet (aminoprotect care) in dogs with spontaneous food allergy. J Vet Med Sci. 2007 Oct;69(10):1025-3114. Smithberg SR, Fogle JE, Mexas AM, Reckling SK, Lankford SM, Tomkins MB, Dean GA. In vivo depletion ofCD4+CD25+ regulatory T cells in cats. J Immunol Methods. 2008 Jan 1;329(1-2):81-91.15. Macias E, Kim Y, Miliani de Marval PL, Klein-Szanto A, Rodriguez-Puebla ML.Cdk2 deficiency decreasesras/CDK4-dependent malignant progression, but not myc-induced tumorigenesis. Cancer Res. 2007 Oct15;67(20):9713-20.16. Newman DR, Walsh E, Apparao KB, Sannes PL. Fibroblast growth factor-binding protein and N-deacetylase/Nsulfotransferase-1expression in type II cells is modulated by heparin and extracellular matrix. Am J Physiol LungCell Mol Physiol. 2007 Nov;293(5):L1314-20.17. Yoder JA, Orcutt TM, Traver D, Litman GW. Structural characteristics of zebrafish orthologs of adaptor moleculesthat associate with transmembrane immune receptors.Gene. 2007 Oct 15;401(1-2):154-64.18. Diniz PP, Maggi RG, Schwartz DS, Cadenas MB, Bradley JM, Hegarty B, Breitschwerdt EB. Caninebartonellosis: serological and molecular prevalence in Brazil and evidence of co-infection with Bartonellahenselae and Bartonella vinsonii subsp. Berkhoffii. Vet Res. 2007 Sep-Oct;38(5):697-710.19. Gabr AA, Reed M, Newman DR, Pohl J, Khosla J, Sannes PL. Alterations in cytoskeletal and immune functionrelatedproteome profiles in whole rat lung following intratracheal instillation of heparin. Respir Res. 2007 May8;8:36.20. Olivry T. A review of autoimmune skin diseases in domestic animals: I - superficial pemphigus.Vet Dermatol.2006 Oct;17(5):291-305. Review21. Olivry T, Deangleo KB, Dunston SM, Clarke KB, McCall CA. Patch testing of experimentally sensitized beagledogs: development of a model for skin lesions of atopic dermatitis. Vet Dermatol. 2006 Apr;17(2):95-10271

Table 3. Publications co-authored by CCMTR members.CCMTRMemberAdler, Ken(KB)Anderson,Ken (KE)Anderson,Ken (KE)Atkins, Clarke(CE)Atkins, Clarke(CE)Atkins, Clarke(CE)Atkins, Clarke(CE)Birkenheuer,Adam (AJ)Birkenheuer,Adam (AJ)Birkenheuer,Adam (AJ)Birkenheuer,Adam (AJ)Birkenheuer,Adam (AJ)Birkenheuer,Adam (AJ)Birkenheuer,Adam (AJ)Birkenheuer,Adam (AJ)Birkenheuer,Adam (AJ)Birkenheuer,Adam (AJ)Birkenheuer,Adam (AJ)Collaborative PublicationsHawkins EC, Birkenheuer AJ, Marr HS, Rogala AR, Large EE, Adler KB. Quantification of mucin geneexpression in tracheobronchial epithelium of healthy dogs and dogs with chronic bronchitis. AmericanJournal of Veterinary Research 2007; 68:435-440.Jackson E, Anderson K, Ashwell C, Petitte J, Mozdziak PE. CA125 expression in spontaneous ovarianadenocarcinomas from laying hens. Gynecol Oncol. 2007Jan;104(1):192-8.Li X, Payne JB, Santos FB, Levine JF, Anderson KE, Sheldon BW. Salmonella populations andprevalence in layer feces from commercial high-rise houses and characterization of the Salmonellaisolates by serotyping, antibiotic resistance analysis, and pulsed field gel electrophoresis. Poult Sci 2007Mar, 86(3):591-7.Atkins, CE, Rausch WP, Gardner SY, Defrancesco TC, Keene BW, Levine JF. The effect ofamlodipine and the combination of amlodipine and enalapril on the renin-angiotensin-aldosterone systemin the dog. J Vet Pharmacol Ther. 2007 Cot1;231(7):1061-9.Fujii Y, Keene BW, Matthews KG, Atkins CE, Defrancesco TC, Hardie EM, Wakao Y. Coil occlusion ofresidual shunts after surgical closure of patent ductus arteriosus. Vet Surg. 2006 Dec;35(8):781-5.Gardner SY, Atkins CE, Rausch WP, DeFrancesco TC, Chander DW, Keene BW. Estimation of 24-haldosterone secretion in the dog using the urine aldosterone:creatinine ratio. J Vet Cardiol. 2007May;9(1):1-7.Johansson AM, Gardner SY, Atkins CE, LaFevers DH, Breuhaus BA. Cardiovascular effects of acutepulmonary obstruction in horses with recurrent airway obstruction. J Vet Intern Med. 2007 Mar-Apr;21(2):302-7.Birkenheuer AJ, Whittington J, Neel J, Large E, Barger A, Levy MG, Breitschwerdt EB. Molecularcharacterization of a Babesia species identified in a North American raccoon. J Wildl Dis. 2006Apr;442(2):375-80.Birkenheuer AJ, Correa MT, Levy MG, Breitschwerdt EB. Development and evaluation of a PCRassay for the detection of Cytauxzoon felis DAN in feline blood samples. Vet Parasitol. 2006Apr15;137(1-2):144-9.Birkenheuer AJ, Harms CA, Neel J, Marr HS, Tucker MD, Acton AE, Tottle AD, Stoskopf MK. Theidentification of a genetically unique piroplasma in North American river otters (Lontra canadensis).Parasitology. 2007 may;134(Pt5):631-5.Birkenheuer AJ, Le JA, Valenzisi AM, Tucker MD, Levy MG, Breitschwerdt EB. Cytauxzoon felisinfection in cats in mid-Atlantic states: 34 cases (1998-2004). J Am Vet Med Assoc. 2006 Feb15;228(4):568-71.Duncan AW, Marr HS, Birkenheuer AJ, Maggi RG, Williams LE, Correa MT, Breitschwerdt EB.Bartonella DNA in the blood and lymph nodes of Golden Retrievers with lymphoma and in healthycontrols. Vet Intern Med. 2008 Jan-Feb;22(1):89-95.Gookin JL, Birkenheuer AJ, St. John V, Spector M, and Levy M.Molecular characterization of trichomonads from feces of dogs with diarrhea. J Parasitol; 2005;91:939-943.Gookin JL, Copple CN, Papich MG, Poore M, Stauffer SH, Birkenheuer AJ, Twedt DC,and Levy MG. Efficacy of ronidazole for treatment of feline Tritrichomonas foetus infection. J Vet InternMed 2006; 20:536-543.PMC1594902.Hawkins EC, Birkenheuer AJ, Marr HS, Rogala AR, Large EE, Adler KB. Quantification of mucin geneexpression in tracheobronchial epithelium of healthy dogs and dogs with chronic bronchitis. AmericanJournal of Veterinary Research 2007; 68:435-440.Hawkins EC, Johnson LR, Guptill L, Marr HS, Breitschwerdt EB, Birkenheuer AB. Failure to identifyan association between serological or molecular evidence of Bartonella spp infection and idiopathicrhinitis in dogs. Journal of the American Veterinary Medical Association. Accepted, January 2008.Puskar M, Lemons C, Papich MG, Vaden SL, Birkenheuer A. Antibiotic-resistant Corynebacteriumjeikeium urinary tract infection in a cat. J Am Anim Hosp Assoc. 2007 Jan-Feb;43(1):61-4.Stauffer SH, Birkenheuer AJ, Levy MG, Marr H, Gookin JL Evaluation of four DNAextraction methods for the detection of Tritrichomonas foetus in feline stool specimens by polymerasechain reaction. J Vet Diagn Invest 2007 In Press.72

Birkenheuer,Adam (AJ)Blikslager,Anthony (AT)Blikslager,Anthony (AT)Blikslager,Anthony (AT)Blikslager,Anthony (AT)Blikslager,Anthony (AT)Blikslager,Anthony (AT)Blikslager,Anthony (AT)Blikslager,Anthony (AT)Breen,MatthewBreen,MatthewBreen,MatthewBreen,MatthewBreitschwerdt,Ed (EB)Breitschwerdt,Ed (EB)Breitschwerdt,Ed (EB)Breitschwerdt,Ed (EB)Breitschwerdt,Ed (EB)Breitschwerdt,Ed (EB)Breitschwerdt,Ed (EB)Valentine KH, Harms CA, Cadenas MB, Birkenheuer AJ, Marr HS, Brau-McNeill J, Maggi RG,Breitschwerdt EB. Bartonella DNA in loggerhead sea turtles. Emerg Infect Dis. 2007 Jun;12(6):949-50.Alward A, Corriher CA, Barton MH, Sellon DC, Blikslager AT, Jones SL. Red maple (Acer rubrum) leaftoxicosis in horses: a retrospective study of 32 cases. J Vet Intern Med. 2006 Sep-Oct;20(5):1197-201.Blikslager AT, Moeser AJ, Gookin JL, Jones SL, Odle J. Restoration of barrier functionin injured intestinal mucosa. Physiological Reviews 2007; 545-564.Corl BA, Odle J, Niu X, Moeser AJ, Gatlin LA, Phillips OT, Blikslager AT, Rhoads JM.Arginine activates intestinal p70(S6k) and protein synthesis in piglet rotavirus enteritis. J Nutr2008;138:24-9Frederico LM, Jones SL, Blikslager AT. Predisposing factors for small colon impaction in horses andoutcome of medical and surgical treatment: 44 cases (1999-2004). J Am Vet Med Assoc. 2006 Nov15;229(10):1612-6.Lascelles BD, Blikslager AT, Fox SM, Reece D. Gastrointestinal tract perforation in dogs treated with aselective cyclooxygenase-2 inhibitor: 29 cases (2002-2003). J Am Vet Med Assoc. 2005 Oct1;227(7):1112-7.Little D, Jones SL, Blikslager AT. Cyclooxygenase (COX) inhibitors and the intestine. J Vet Intern Med.2007 May-Jun;21(3):367-77.Rhoads JM, Corl BA, Harrell R, Niu X, Gatlin L, Phillips O, Blikslager AT, Moeser A, Wu G,Odle J. Intestinal ribosomal p70(S6K) signaling is increased in piglet rotavirus enteritis.Am J Physiol Gastrointest Liver Physiol 2007;292:G913-22.Wooten JG, Blikslager AT, Ryan KA, Marks SL, Law JM, Lascelles BD. Cyclooxygenaseexpression and prostanoid production in pyloric and duodenal mucosae in dogs after administration ofnonsteroidal anti-inflammatory drugs. Am J Vet Res 2008;69:457-64.Kisseberth WC, Nadella MV, Breen M, Thomas R, Duke SE, Murahari S, Kosarek CE,Vernau W, Avery AC, Burkhard MJ, Rosol TJ. A novel canine lymphoma cell line: atranslational and comparative model for lymphoma research. Leuk Res. 2007 Dec;31(12):1709-20.Thomas R, Duke SE, Bloom SK, Breen TE, Young AC, Fieste E, Seiser EL, Tsai PC,Langford CF, Ellis P, Karlsson EK, Lndblad-Toh K, Breen M. A cytogenetically characterized, genomeanchored10-Mb BAC set and CGH array for the domestic dog. J Hered. 2007;98(5):474-84.Thomas R, Scott A, Langford DF, Fosmire SP, Jubala CM, Loretzen TD, Hitte C, Karlsson EK, KirknessE, Ostrander EA, Galibert F, Lindblad-Toh K, Modiano JF, Breen M. Construction of a 2-Mb resoluctionBAC microarray for CGH analysis of canine tumors. Genome Res. 2005 Dec;15(12):1831-7.Zaunbrecher G, Mir B, Dunne PW, Breen M, Piedrahita JA. 2008. Enhancement of extrachromosomal recombination in somatic cells by affecting the ratio of homologous recombination (HR) tonon-homologous end joining (NHEJ). Animal Biotechnology 19:6-21.Billeter SA, Blanton HL, Little SE, Levy MG, Breitschwerdt EB. Detection of Rickettsia amblyommii inassociation with a tick bite rash. Vector Borne Zoonotic Dis. 2007 Winter;7(4):607-10.Billeter SA, Levy MG, Chomel BB, Breitschwerdt EB. Vector transmission of Bartonella species withemphasis on the potential for tick transmission.Med Vet Entomol. 2008 Mar;22(1):1-15Billeter SA, Miller MK, Breitschwerdt EB, Levy MG. Detection of two Bartonella tamiae-like sequencesin Amblyomma americanum (Acari: Ixodidae) using 16S-23S intergenic spacer region-specific primers. JMed Entomol. 2008 Jan;45(1):176-9.Birkenheuer AJ, Whittington J, Neel J, Large E, Barger A, Levy MG, Breitschwerdt EB. Molecularcharacterization of a Babesia species identified in a North American raccoon. J Wildl Dis. 2006Apr;442(2):375-80.Birkenheuer AJ, Correa MT, Levy MG, Breitschwerdt EB. Development and evaluation of a PCRassay for the detection of Cytauxzoon felis DAN in feline blood samples. Vet Parasitol. 2006Apr15;137(1-2):144-9.Birkenheuer AJ, Le JA, Valenzisi AM, Tucker MD, Levy MG, Breitschwerdt EB. Cytauxzoon felisinfection in cats in mid-Atlantic states: 34 cases (1998-2004). J Am Vet Med Assoc. 2006 Feb15;228(4):568-71.Duncan AW, Marr HS, Birkenheuer AJ, Maggi RG, Williams LE, Correa MT, Breitschwerdt EB.Bartonella DNA in the blood and lymph nodes of Golden Retrievers with lymphoma and in healthycontrols. Vet Intern Med. 2008 Jan-Feb;22(1):89-95.73

Breitschwerdt,Ed (EB)Breitschwerdt,Ed (EB)Breitschwerdt,Ed (EB)Breitschwerdt,Ed (EB)Breitschwerdt,Ed (EB)Breitschwerdt,Ed (EB)Cullen, John(JM)Cullen, John(JM)Davidian,MarieDavidian,MarieDavidian,MarieDavidian,MarieDean, Gregg(GA)Dean, Gregg(GA)Dean, Gregg(GA)Dean, Gregg(GA)Deiters, AlexDeiters, AlexFarin,Charlotte(CE)Farin,Charlotte(CE)Farin,Charlotte(CE)Farin, Peter(PW)Hawkins EC, Johnson LR, Guptill L, Marr HS, Breitschwerdt EB, Birkenheuer AB. Failure to identifyan association between serological or molecular evidence of Bartonella spp infection and idiopathicrhinitis in dogs. Journal of the American Veterinary Medical Association. Accepted, January 2008.Hess PR, English RV, Hegarty BC, Brown GD, Breitschwerdt EB. Experimental Ehrlichia canisinfection in the dog does not cause immunosuppression. Vet Immunol Immunopathol. 2006 Jan15;109(1-2):117-25.Hill TL, Breitschwerdt EB, Cecere T, Vaden S. Concurrent hepatic copper toxicosis and Fanconi'ssyndrome in a dog. J Vet Intern Med. 2008 Jan-Feb;22(1):219-22Jones SL, Maggi R, Shuler J, Alward A, Breitschwerdt EB. Detection of Bartonella henselae in theblood of 2 adult horses. J Vet Intern Med. 2008 Mar-Apr;22(2):495-8.Jones SL, Valenzisi A, Sontakke S, Sprayberry KA, Maggi R, Hegarty B, Breitschwerdt E. Use of aninsect cell culture growth medium to isolate bacteria from horses with effusive, fibrinous pericarditis: apreliminary study. Vet Microbiol. 2007 Mar 31;121(1-2):177-81.Valentine KH, Harms CA, Cadenas MB, Birkenheuer AJ, Marr HS, Brau-McNeill J, Maggi RG,Breitschwerdt EB. Bartonella DNA in loggerhead sea turtles. Emerg Infect Dis. 2007 Jun;12(6):949-50.Hess PR, Barnes C, Woolard MD, Johnson MD, Cullen JM, Collins EJ, and Frelinger JA..Selective deletion of antigen-specific CD8 + T cells by MHC class I tetramers coupled to the type Iribosome-inactivating protein saporin. Blood 2007;109(8):3300-3307.Marcias E, de Marval PL, Senderowicz A, Cullen J, Rodriguez-Puebla, ML. Expression of CDK4 orCDK2 in mouse oral cavity is retained in adult pituitary with distinct effects on tumorigenesis. CancerRes. 2008 Jan 1;68(1):162-71.Lin J, Zhang D, Davidian M. Smoothing spline-based score tests for proportional hazards models.Biometrics. 2006 Sep;62(3):803-12Tsiatis AA, Davidian M, Zhang M, Lu X. Covariate adjustment for two-sample treatment comparisons inrandomized clinical trials: A principled yet flexible approach. Stat Med. 2007 Oct 24.Tsiatis AA, Davidian M. Comment: Demystifying Double Robustness: A Comparison of AlternativeStrategies for Estimating a Population Mean from Incomplete Data.Stat Sci. 2007;22(4):569-573.Zhang M, Tsiatis AA, Davidian M. Improving Efficiency of Inferences in Randomized Clinical TrialsUsing Auxiliary Covariates. 2008 Jan 11. [Epub ahead of print]Nordone SK, Ignacio GA, Su L, Sempowski GD, Golenbock DT, Li L, Dean GA. Failure of TLR4-drivenNF-kappa B activation to stimulate virus replication in models of HIV type 1 activation. AIDS Res HumRetroviruses. 2007 Nov;23(11):1387-95.Olivry T, LaVoy A, Dunston SM, Brown RS, Lennon EM, Warren SJ, Prisayanh P, Muller EJ, Suter MM,Dean GA. Desmoglein-1 is a minor autoantigen in dogs with pemphigus foliaceus. Vet ImmunolImmunopathol. 2006 Apr 15;110(3-4):245-55.Smithberg SR, Fogle JE, Mexas AM, Reckling SK, Lankford SM, Tompkins MB, Dean GA. In vivodepletion of CD4+CD25+ regulatory T cells in cats. Vet Immunol Immunopathol. 2008 Mar 14;122(1-2):159-66.Yearley JH, Stanton C, Olivry T, Dean GA. Phagocytic plasmacytoma in a dog. Vet Clin Pathol. 2007Sep;36(3):293-6.Deiters A, Yoder JA. 2006. Conditional transgene and gene targeting methodologiesin zebrafish. Zebrafish. 3: 415-429Young DD, Lusic H, Lively MO, Yoder JA, Deiters A. 2008. Gene Silencing with Light-ActivatedAntisense Agents. Submitted.Farin CE, Rodriguez KF, Alexander JE, Hockney JE, Herrick JR, Kennedy-Stoskopf S. The role oftranscription in EGF- and FSH-mediated oocyte maturation in vitro.Anim Reprod Sci. 2007 Mar;98(1-2):97-112.Farin PW, Piedrahita JA, Farin CE. Errors in development of fetuses and placentas from in vitroproducedbovine embryos.Theriogenology. 2006 Jan 7;65(1):178-91.Whang HS, Hunt MA, Medlin E, Wrench N, Hockney J, Farin CE, and Tonelli AE, J. Nonoxynol-9-α-Cyclodextrin Inclusion Compound and its Application for the Controlled Release of Nonoxynol-9Spermicide, Appl. Polym. Sci., 106, 4104, 2007.Farin PW, Piedrahita JA, Farin CE. Errors in development of fetuses and placentas from in vitroproducedbovine embryos.Theriogenology. 2006 Jan 7;65(1):178-91.74

Gardner,Sarah (SY)Gardner,Sarah (SY)Gardner,Sarah (SY)Gilger, Brian(BC)Gilger, Brian(BC)Gilger, Brian(BC)Gilger, Brian(BC)Gilger, Brian(BC)Gookin, JodyGookin, JodyGookin, JodyGookin, JodyGookin, JodyGookin, JodyGookin, JodyGookin, JodyHammerberg,BruceHammerberg,BruceAtkins, CE, Rausch WP, Gardner SY, Defrancesco TC, Keene BW, Levine JF. The effect ofamlodipine and the combination of amlodipine and enalapril on the renin-angiotensin-aldosterone systemin the dog. J Vet Pharmacol Ther. 2007 Cot1;231(7):1061-9.Gardner SY, Atkins CE, Rausch WP, DeFrancesco TC, Chander DW, Keene BW. Estimation of 24-haldosterone secretion in the dog using the urine aldosterone:creatinine ratio. J Vet Cardiol. 2007May;9(1):1-7.Johansson AM, Gardner SY, Atkins CE, LaFevers DH, Breuhaus BA. Cardiovascular effects of acutepulmonary obstruction in horses with recurrent airway obstruction. J Vet Intern Med. 2007 Mar-Apr;21(2):302-7.Acton AE, Beale AB, Gilger BC, Stoskopf MK. Sustained release cyclosporine therapy for bilateralkeratoconjunctivitis sicca in a red wolf (Canis rufus). Invest Ophthalmol Vis Sci. 2007 May;48(5):2023-9.Bakal RS, Hickson BH, Gilger BC, Levy MG, Flowers JR, Khoo L. Surgical removal of cataracts due toDiplostomum species in Gulf sturgeon (Acipenser oxyrinchus desotoi). J Zoo Wildl Med. 2006Dec;37(4):562-4.Beale AB, Salmon J, Michau TM, Gilger BC. Effect of ophthalmic Nd:YAG laser energy on intraocularlenses after posterior capsulotomy in normal dog eyes. Vet Ophthalmol. 2006 Sep-Oct;9(5):335-40.Clode AB, Davis JL, Salmon J, Michau TM, Gilger BC. Evaluation of concentration of voriconazole inaqueous humor after topical and oral administration in horses. Am J Vet Res. 2006 Feb;67(2):296-301.Ng YF, Chan HH, Chu PH, To CH, Gilger BC, Petters RM, Wong F. Multifocalelectroretinogram in rhodopsin P347L transgenic pigs. Invest Ophthalmol Vis Sci. 2008 May;49(5):2208-15.Blikslager AT, Moeser AJ, Gookin JL, Jones SL, Odle J. Restoration of barrier functionin injured intestinal mucosa. Physiological Reviews 2007; 545-564.Gookin JL, Birkenheuer AJ, St. John V, Spector M, and Levy M.Molecular characterization of trichomonads from feces of dogs with diarrhea. J Parasitol; 2005;91:939-943.Gookin JL, Copple CN, Papich MG, Poore M, Stauffer SH, Birkenheuer AJ, Twedt DC,and Levy MG. Efficacy of ronidazole for treatment of feline Tritrichomonas foetus infection. J Vet InternMed 2006; 20:536-543.PMC1594902.Gookin JL, Stauffer SH, Coccaro MR, Marcotte M, Levy MG. Optimization of aspecies-specific PCR assay for identification of Pentatrichomonas hominis in canine fecal specimens. AmJ Vet Res 2007;68:783-787.Gookin JL, Stauffer SH, Coccaro MR, Poore MF, Levy MG, Papich MG. Efficacy oftinidazole for treatment of cats experimentally infected with Tritrichomonas foetus. Am J Vet Res;2007;68:1085-1088.Gookin JL, Stauffer SH, Levy MG. Identification of Pentatrichomonas hominis in felinefecal samples by polymerase chain reaction assay. Vet Parasitol; 2007;145,11-15.Stauffer SH, Birkenheuer AJ, Levy MG, Marr H, Gookin JL Evaluation of four DNAextraction methods for the detection of Tritrichomonas foetus in feline stool specimens by polymerasechain reaction. J Vet Diagn Invest 2007 In Press.Zadrozny LM, Stauffer SH, Armstrong MU, Jones SL, Gookin JL. Neutrophils do notmediate the pathophysiological sequelae of C. parvum infection in neonatal piglets. Infect Immun 2006;74:5497-5505.Olivry T, Dunston SM, Pluchino K, Porter K, Hammberberg B. Lack of detection of circulating skinspecificIgE autoantibodies in dogs with moderate or severe atopic dermatitis.Vet ImmunolImmunopathol. 2008 Mar 15;122(1-2):182-7.Olivry T, Mueller R, Nuttall T, Favrot C, Prelaud P, International Task Force on Canine Atopic Dermatitis.Collaborators: Bensignor E, Carlotti D, DeBeor D, Favrot C, Griffin C, Halliwell R, Hammerberg B, Hill P,Iwasaki T, Jackson H, Maeda S, Masuda R, Mueller R, Nuttall T, Olivry T, Prelaud P, Sousa C, WillemseT. Determination of CADESI-03 thresholds for increasing severity levels of canine atopic dermatitis. VetDermatol. 2008 Jun;19(3):115-9.75

Hammerberg,BruceHammerberg,BruceHardie,Lizette (EM)Hardie,Lizette (EM)Hardie,Lizette (EM)Hauck,Marlene (ML)Hauck,Marlene (ML)Hauck,Marlene (ML)Hawkins,Eleanor (EC)Hawkins,Eleanor (EC)Hawkins,Eleanor (EC)Hawkridge,Adam (AM)Hawkridge,Adam (AM)Hawkridge,Adam (AM)Hawkridge,Adam (AM)Hawkridge,Adam (AM)Hawkridge,Adam (AM)Hawkridge,Adam (AM)Pucheu-Haston CM, Jackson HA, Olivry T, Dunston SM, Hammerberg B. Epicutaneous sensitizationwith Dermatophagoides farinae induces generalized allergic dermatitis and elevated mite-specificimmunoglobulin E levels in a canine model of atopic dermatitis. Clin Exp Allergy. 2008 Apr;38(4):667-79.Pucheu-Haston CM, Shuster D, Olivry T, Brianceau P, Lockwood P, McClanahan T, de Waal Malefyt R.Mattson JD, Hammerberg B. A canine model of cutaneous late-phase reactions: prednisolone inhibitionof cellular and cytokine responses. Immunology. 2006Feb;117(2):177-87.Davis KM, Hardie EM, Lascelles BD, Hansen. Feline fibrosarcoma: perioperativemanagement. Compend Contin Educ Vet. 2007 Dec;29(12):712-4, 716-20, 722-9Fujii Y, Keene BW, Matthews KG, Atkins CE, Defancesco TC, Hardie EM, Wakao Y. Coil occlusion ofresidual shunts after surgical closure of patent ductus arteriosus. Vet Surg. 2006 Dec;35(8):781-5.Lascelles BD, Court MH, Hardie EM, Robertson SA. Nonsteroidal anti-inflammatory drugs in cats: areview. Vet Anaesth Analg. 2007 Jul;34(4):228-50.Hauck ML, LaRue SM, Petros WP, Poulson JM, Yu D, Spasojevic I, Pruitt AF, Klein A,Case B, Thrall DE, Needham D, Dewhirst MW. Phase I trial of doxorubicin-containing low temperaturesensitive liposomes in spontaneous canine tumors. Clin Cancer Res. 2006 Jul 1;12(13):4004-10.Kleiter MM, Yu D, Mohammadian LA, Niehaus N, Spasojevic J, Sanders L, Viglianti BL, Yarmolenko PS,Hauck M, Petry NA, Wong TZ, Dewhirst MW, Thrall DE. A tracer dose of technetium-99m-labeledliposomes can estimate the effect of hyperthermia on intratumoral doxil extravasation. Clin Cancer Res.2006 Nov 15;12(22):6800-7.Siddiqui F, Li CY, Larue SM, Poulson JM, Avery PR, Pruitt AF, Zhang X, Ullrich RL, ThrallDE, Dewhirst MW, Hauck ML. A phase I trial of hyperthermia-induced interleukin-12 gene therapy inspontaneously arising feline soft tissue sarcomas.Mol Cancer Ther. 2007 Jan;6(1):380-9.Hawkins EC, Birkenheuer AJ, Marr HS, Rogala AR, Large EE, Adler KB. Quanitfication of mucin geneexpression in tracheobronchial epithelium of healthy dogs and dogs with chronic bronchitis. AmericanJournal of Veterinary Research 2007; 68:435-440.Hawkins EC, Johnson LR, Guptill L, Marr HS, Breitschwerdt EB, Birkenheuer AB. Failure to identifyan association between serological or molecular evidence of Bartonella spp infection and idiopathicrhinitis in dogs. Journal of the American Veterinary Medical Association. Accepted, January 2008.Mexas AM, Hess RS, Hawkins EC, Martin LD. Pulmonary lesions in cats with diabetes mellitus. J VetIntern Med. 2006 Jan-Feb;20(1):47-51.Caskey DC, Yamamoto T, Addicott C, Shoemaker RK, Vacek J, Hawkridge AM,Muddiman DC, Kottas GS, Michl J, Stang PJ. Coordination-driven face-directedself-assembly of trigonal prisms. Face-based conformational chirality. J Am Chem Soc.2008 Jun 18;130(24):7620-8.Collier TS, Hawkridge AM, Georgianna DR, Payne GA, Muddiman DC. Top-down identification andquantification of stable isotope labeled proteins from Aspergillus flavus using online nano-flow reversedphaseliquid chromatography coupled to a LTQ-FTICR mass spectrometer. Anal Chem. 2008 Jul1;80(13):4994-5001.Dixon RB, Bereman MS, Muddiman DC, Hawkridge AM. Remote mass spectrometric sampling ofelectrospray- and desorption electrospray-generated ions using an air ejector. J Am Soc Mass Spectrom.2007 Oct;18(10):1844-7.Dixon RB, Muddiman DC, Hawkridge AM, Fedorov AG. Probing the mechanisms of an air amplifierusing a LTQ-FT-ICR-MS and fluorescence spectroscopy. Am Soc Mass Spectrom. 2007Nov;18(11):1909-13.Dixon RB, Sampson JS, Hawkridge AM, Muddiman DC. Ambient aerodynamic ionization source forremote analyte sampling and mass spectrometric analysis. Anal Chem. 2008 Jul 1;80(13):5266-71.Georgianna DR, Hawkridge AM, Muddiman DC, Payne GA. Temperature-Dependent Regulation ofProteins in Aspergillus flavus: Whole Organism Stable Isotope Labeling by Amino Acids. J ProteomeRes. 2008 Jul;7(7):2973-9.Hawkridge AM, Heublein DM Bergen HR 3rd, Cataliotti A, Burnett JC Jr, Muddiman DC. Quantitativemass spectral evidence for the absence of circulating brain natriuretic peptide(BNP-32) in severe human heart failure. Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17442-7.76

Hawkridge,Adam (AM)Hawkridge,Adam (AM)Hawkridge,Adam (AM)Hawkridge,Adam (AM)Hawkridge,Adam (AM)Hawkridge,Adam (AM)Hawkridge,Adam (AM)Hawkridge,Adam (AM)Hawkridge,Adam (AM)Hawkridge,Adam (AM)Hess, PaulHess, PaulHoward,Kristina (KE)Jones, Sam(SL)Jones, Sam(SL)Jones, Sam(SL)Jones, Sam(SL)Jones, Sam(SL)Jones, Sam(SL)Hawkridge AM, Muddiman DC, Hebulein DM, Cataliotti A< Burnett JC Jr. Effect of plasma proteindepletion on BNP-32 recovery. Clin Chem. 2008 May;54(5):933-4.Kang S, Hawkridge AM, Johson KL, Muddiman DC, Prevelige PE Jr. Identification of subunit-subunitinteractions in bacteriophage P22 procapsids by chemical cross-linking and mass spectrometry. JProteome Res. 2006 Feb;5(2):370-7.Sampson JS, Hawkridge AM, Muddiman DC. Direct characterization of intact polypeptidesby matrix-assisted laser desorption electrospray ionization quadrupole Fourier transform ion cyclotronresonance mass spectrometry. Rapid Commun Mass Spectrom.2007;21(7):1150-4.Sampson JS, Hawkridge AM, Muddiman DC. Generation and detection of multiply-charged peptidesand proteins by matrix-assisted laser desorption electrospray ionization (MALDESI) Fourier transform ioncyclotron resonance mass spectrometry. J Am Soc Mass Spectrom. 2006 Dec;17(12):1712-6.Williams DK Jr, Hawkridge AM, Muddiman DC. Sub parts-per-million mass measurement accuracy ofintact proteins and product ions achieved using a dual electrospray ionization quadrupole fouriertransform ion cyclotron resonance mass spectrometer. J Am Soc Mass Spectrom. 2007 Jan;18(1):1-7.Williams DK Jr, Meadows CW, Bori ID, Hawkridge AM Comins DL, Muddiman DC. Synthesis,characterization, and application of iodoacetamide derivatives utilized for the ALiPHAT strategy. J AmChem Soc. 2008 Feb 20;130(7):2122-3.Yang HB, Das N, Huang F, Hawkridge AM, Diaz DD, Arif AM Finn MG, Muddiman DC,Stang PJ. Incorporation of 2,6-di(4,4'-dipyridyl)-9-thiabicyclo[3.3.1]nonane into discrete 2Dsupramolecules via coordination-driven self-assembly.J Org Chem. 2006 Aug 18;71(17):6644-7.Yang HB, Das N, Huang F, Hawkridge AM, Muddiman DC, Stang PJ. Molecular architecture viacoordination: self-assembly of nanoscale hexagonal metallodendrimers with designed building blocks. JAm Chem Soc. 2006 Aug 9;128(31):10014-5.Yang HB, Hawkridge AM, Haung SD, Das N, Bunge SD, Muddiman DC, Stang PJ. Coordination-drivenself-assembly of metallodendrimers possessing well-defined and controllable cavities as cores. J AmChem Soc. 2007 Feb 21;129(7):2120-9.Yang P, Cooks RG, Ouyang Z, Hawkridge AM, Muddiman DC. Gentle protein ionization assisted byhigh-velocity gas flow. Anal Chem. 2005 Oct 1;77(19):6174-83.Hess PR, Barnes C, Woolard MD, Johnson MD, Cullen JM, Collins EJ, and Frelinger JA..Selective deletion of antigen-specific CD8 + T cells by MHC class I tetramers coupled to the type Iribosome-inactivating protein saporin. Blood 2007;109(8):3300-3307.Hess PR, English RV, Hegarty BC, Brown GD, Breitschwerdt EB. Experimental Ehrlichia canisinfection in the dog does not cause immunosuppression. Vet Immunol Immunopathol. 2006 Jan15;109(1-2):117-25.Zurney, J., K.E. Howard, and B. Sherry. 2007. Basal expression of IFNAR and Jak-STATcomponents are determinants of cell type-specific differences in the cardiac antiviral response. Journalof Virology, 81:13668-13680.Alward A, Corriher CA, Barton MH, Sellon DC, Blikslager AT, Jones SL. Red maple (Acer rubrum) leaftoxicosis in horses: a retrospective study of 32 cases. J Vet Intern Med. 2006 Sep-Oct;20(5):1197-201.Blikslager AT, Moeser AJ, Gookin JL, Jones SL, Odle J. Restoration of barrier functionin injured intestinal mucosa. Physiological Reviews 2007; 545-564.Frederico LM, Jones SL, Blikslager AT. Predisposing factors for small colon impaction in horses andoutcome of medical and surgical treatment: 44 cases (1999-2004). J Am Vet Med Assoc. 2006 Nov15;229(10):1612-6.Jones SL, Maggi R, Shuler J, Alward A, Breitschwerdt EB. Detection of Bartonella henselae in theblood of 2 adult horses. J Vet Intern Med. 2008 Mar-Apr;22(2):495-8.Jones SL, Valenzisi A, Sontakke S, Sprayberry KA, Maggi R, Hegarty B, Breitschwerdt E. Use of aninsect cell culture growth medium to isolate bacteria from horses with effusive, fibrinous pericarditis: apreliminary study. Vet Microbiol. 2007 Mar 31;121(1-2):177-81.Little D, Jones SL, Blikslager AT. Cyclooxygenase (COX) inhibitors and the intestine. J Vet Intern Med.2007 May-Jun;21(3):367-77.77

Jones, Sam(SL)Kennedy-Stoskopf,SuzanneKennedy-Stoskopf,SuzanneKennedy-Stoskopf,SuzanneKennedy-Stoskopf,SuzanneKennedy-Stoskopf,SuzanneKim,YongbaekLalush, David(DS)Lascelles,Duncan (BD)Lascelles,Duncan (BD)Lascelles,Duncan (BD)Lascelles,Duncan (BD)Lascelles,Duncan (BD)Law, Mac(JM)Law, Mac(JM)Law, Mac(JM)Law, Mac(JM)Law, Mac(JM)Levine, Jay(JF)Levine, Jay(JF)Zadrozny LM, Stauffer SH, Armstrong MU, Jones SL, Gookin JL. Neutrophils do notmediate the pathophysiological sequelae of C. parvum infection in neonatal piglets. Infect Immun 2006;74:5497-5505.Farin CE, Rodriguez KF, Alexander JE, Hockney JE, Herrick JR, Kennedy-Stoskopf S. The role oftranscription in EGF- and FSH-mediated oocyte maturation in vitro.Anim Reprod Sci. 2007 Mar;98(1-2):97-112.Henson-Ramsey H, Kennedy-Stoskopf S, Levine JF, Shea D, Talylor SK, Stoskopf MK. A comparisonof two exposure systems to apply malathion to Lumbricus terrestris L. Bull Environ Contam Toxicol. 2007Jun;78(6):427-31. Epub 2007 Jul 7.Henson-Ramsey H, Kennedy-Stoskopf S, Levine JF, Taylor SK, Shea D, Stoskopf MK. Acute Toxicityand Tissue Distributions of Malathion in Ambystoma tigrinum. Arch Environ Contam Toxicol. 2008 Jan29.Henson-Ramsey H, Shea D, Levine JF, Kennedy-Stoskopf S, Taylor SK, Stoskopf MK. Assessment ofthe effect of varying soil organic matter content on the bioavailability of malathion to the commonnightcrawler, Lumbricus terrestris L. Bull Environ Contam Toxicol. 2008 Mar;80(3):220-4. Epub 2008 Jan19Wolf KN, DePerrio CS, Jenks JA, Stoskopf MK, Kennedy-Stoskopf S, Swanson CC,Brinkman TJ, Osborn RG, Tardiff JA. Selenium status and antibodies to selected pathogensin white-tailed deer (Odocoileus virginianus) in Southern Minnesota. J Wildl Dis. 2008 Jan;44(1):181-7.Macias E, Kim Y, Miliani de Marval PL, Klein-Szanto A, Rodriguez-Puebla ML. (2007)Cdk2 deficiency decreases ras/CDK4-dependent malignant progression, but not myc-inducedtumorigenesis. Cancer Res. 67(20):9713-20Pfeiler TW, Lalush DS, Loboa EG. Semiautomated finite element mesh generation methods for a longbone.Comput Methods Programs Biomed. 2007 Mar;85(3):196-202.Davis KM, Hardie EM, Lascelles BD, Hansen. Feline fibrosarcoma: perioperativemanagement. Compend Contin Educ Vet. 2007 Dec;29(12):712-4, 716-20, 722-9Lascelles BD, Blikslager AT, Fox SM, Reece D. Gastrointestinal tract perforation in dogs treated with aselective cyclooxygenase-2 inhibitor: 29 cases (2002-2003). J Am Vet Med Assoc. 2005 Oct1;227(7):1112-7.Lascelles BD, Court MH, Hardie EM, Robertson SA. Nonsteroidal anti-inflammatory drugs in cats: areview. Vet Anaesth Analg. 2007 Jul;34(4):228-50.Royal LW, Grafinger MS, Lascelles BD, Lewbart GA, Christian LS. Internal fixation of a femur fracturein an American bullfrog. J Am Vet Med Assoc. 2007 Apr 15;230(8):1201-4.Wooten JG, Blikslager AT, Ryan KA, Marks SL, Law JM, Lascelles BD. Cyclooxygenaseexpression and prostanoid production in pyloric and duodenal mucosae in dogs after administration ofnonsteroidal anti-inflammatory drugs. Am J Vet Res 2008;69:457-64.Johnson AK, Harms CA, Levine JF, Law JM. A quantitative real-time RT-PCR assay to measure TGFbetamRNA and its correlation with hematologic, plasma chemistry and organo-somatic indicesresponses in triamcinolone-treated Atlantic menhaden, Brevoortia tyrannus. Dev Comp Immunol.2006;30(5):473-84.Johnson AK, Law JM, Harms CA, Levine JF. Multitiered health assessment of Atlantic menhaden in thePamlico River, North Carolina. J Aquat Anim Health. 2007 Dec;19(4):205-14.Lehmann DW, Levine JF, Law J McHugh. Polychlorinated biphenyl exposure causesgonadal atrophy and oxidative stress in Corbicula fluminea clams.Toxicol Pathol. 2007;35(3):356-65.Tuttle AD, Law JM, Harms CA, Lewbart GA, Harvey SB. Evaluation of the gross and histologicreactions to five commonly used suture materials in the skin of the African clawed frog (Xenopus laevis).J Am Assoc Lab Anim Sci. 2006 Nov;45(6):22-6.Wooten JG, Blikslager AT, Ryan KA, Marks SL, Law JM, Lascelles BD. Cyclooxygenaseexpression and prostanoid production in pyloric and duodenal mucosae in dogs after administration ofnonsteroidal anti-inflammatory drugs. Am J Vet Res 2008;69:457-64.Atkins, CE, Rausch WP, Gardner SY, Defrancesco TC, Keene BW, Levine JF. The effect ofamlodipine and the combination of amlodipine and enalapril on the renin-angiotensin-aldosterone systemin the dog. J Vet Pharmacol Ther. 2007 Cot1;231(7):1061-9.Gustafson L, Showers W, Kak T, Levine J, Stoskopf M. Temporal and spatial variability in stableisotope compositions of a freshwater mussel: implications for biomonitoring and ecological studies.Oecologia. 2007 May;152(1):140-50.78

Levine, Jay(JF)Levine, Jay(JF)Levine, Jay(JF)Levine, Jay(JF)Levine, Jay(JF)Levine, Jay(JF)Levine, Jay(JF)Levine, Jay(JF)Levine, Jay(JF)Levy, Mike(MG)Levy, Mike(MG)Levy, Mike(MG)Levy, Mike(MG)Levy, Mike(MG)Levy, Mike(MG)Levy, Mike(MG)Levy, Mike(MG)Levy, Mike(MG)Levy, Mike(MG)Henson-Ramsey H, Kennedy-Stoskopf S, Levine JF, Shea D, Talylor SK, Stoskopf MK. A comparisonof two exposure systems to apply malathion to Lumbricus terrestris L. Bull Environ Contam Toxicol. 2007Jun;78(6):427-31. Epub 2007 Jul 7.Henson-Ramsey H, Kennedy-Stoskopf S, Levine JF, Taylor SK, Shea D, Stoskopf MK. Acute Toxicityand Tissue Distributions of Malathion in Ambystoma tigrinum. Arch Environ Contam Toxicol. 2008 Jan29.Henson-Ramsey H, Shea D, Levine JF, Kennedy-Stoskopf S, Taylor SK, Stoskopf MK. Assessment ofthe effect of varying soil organic matter content on the bioavailability of malathion to the commonnightcrawler, Lumbricus terrestris L. Bull Environ Contam Toxicol. 2008 Mar;80(3):220-4. Epub 2008 Jan19Johnson AK, Harms CA, Levine JF, Law JM. A quantitative real-time RT-PCR assay to measure TGFbetamRNA and its correlation with hematologic, plasma chemistry and organo-somatic indicesresponses in triamcinolone-treated Atlantic menhaden, Brevoortia tyrannus. Dev Comp Immunol.2006;30(5):473-84.Johnson AK, Law JM, Harms CA, Levine JF. Multitiered health assessment of Atlantic menhaden in thePamlico River, North Carolina. J Aquat Anim Health. 2007 Dec;19(4):205-14.Lehmann DW, Levine JF, Law J McHugh. Polychlorinated biphenyl exposure causesgonadal atrophy and oxidative stress in Corbicula fluminea clams.Toxicol Pathol. 2007;35(3):356-65.Li X, Payne JB, Santos FB, Levine JF, Anderson KE, Sheldon BW. Salmonella populations andprevalence in layer feces from commercial high-rise houses and characterization of the Salmonellaisolates by serotyping, antibiotic resistance analysis, and pulsed field gel electrophoresis. Poult Sci 2007Mar, 86(3):591-7.Miller O, Fuller FJ, Gebreyes WA, Lewbart GA, Shchelkunov IS< Shivappa RB, Joiner C, Woolford G,Stone DM, Dixon PF, Raley ME, Levine JF. Phylogenetic analysis of spring virema of carp virus revealsdistinct subgroups with common origins for recent isolates in North America and the UK. Dis AquatOrgan. 2007 Jul 16;76(3):193-204.Vaden SL, Levine JF, Lees GE, Groman RP, Grauer GF, Forrester SD. Renal biopsy: a retrospectivestudy of methods and complications in 283 dogs and 65 cats. J Vet Intern Med. 2005 Nov-Dec;19(6):794-801.Bakal RS, Hickson BH, Gilger BC, Levy MG, Flowers JR, Khoo L. Surgical removal of cataracts due toDiplostomum species in Gulf sturgeon (Acipenser oxyrinchus desotoi). J Zoo Wildl Med. 2006Dec;37(4):562-4.Billeter SA, Blanton HL, Little SE, Levy MG, Breitschwerdt EB. Detection of Rickettsia amblyommii inassociation with a tick bite rash. Vector Borne Zoonotic Dis. 2007 Winter;7(4):607-10.Billeter SA, Levy MG, Chomel BB, Breitschwerdt EB. Vector transmission of Bartonellaspecies with emphasis on the potential for tick transmission.Med Vet Entomol. 2008 Mar;22(1):1-15Billeter SA, Miller MK, Breitschwerdt EB, Levy MG. Detection of two Bartonella tamiae-like sequencesin Amblyomma americanum (Acari: Ixodidae) using 16S-23S intergenic spacer region-specific primers. JMed Entomol. 2008 Jan;45(1):176-9.Birkenheuer AJ, Whittington J, Neel J, Large E, Barger A, Levy MG, Breitschwerdt EB. Molecularcharacterization of a Babesia species identified in a North American raccoon. J Wildl Dis. 2006Apr;442(2):375-80.Birkenheuer AJ, Correa MT, Levy MG, Breitschwerdt EB. Development and evaluation of a PCRassay for the detection of Cytauxzoon felis DAN in feline blood samples. Vet Parasitol. 2006Apr15;137(1-2):144-9.Birkenheuer AJ, Le JA, Valenzisi AM, Tucker MD, Levy MG, Breitschwerdt EB. Cytauxzoon felisinfection in cats in mid-Atlantic states: 34 cases (1998-2004). J Am Vet Med Assoc. 2006 Feb15;228(4):568-71.Gookin JL, Birkenheuer AJ, St. John V, Spector M, and Levy M.Molecular characterization of trichomonads from feces of dogs with diarrhea. J Parasitol; 2005;91:939-943.Gookin JL, Stauffer SH, Coccaro MR, Marcotte M, Levy MG. Optimization of aspecies-specific PCR assay for identification of Pentatrichomonas hominis in canine fecal specimens. AmJ Vet Res 2007;68:783-787.Gookin JL, Stauffer SH, Coccaro MR, Poore MF, Levy MG, Papich MG. Efficacy oftinidazole for treatment of cats experimentally infected with Tritrichomonas foetus. Am J Vet Res;2007;68:1085-1088.79

Levy, Mike(MG)Levy, Mike(MG)Levy, Mike(MG)Levy, Mike(MG)Lewbart, Greg(GA)Lewbart, Greg(GA)Lewbart, Greg(GA)Lewbart, Greg(GA)Li, LexinLinder, Keith(KE)Linder, Keith(KE)Loboa,Elizabeth(EG)Loboa,Elizabeth(EG)Marks, SteveMartin, Linda(LD)Martin, Linda(LD)Michau,Tammy MillerMichau,Tammy MillerMozdziak,Paul (PE)Mozdziak,Paul (PE)Mozdziak,Paul (PE)Gookin JL, Stauffer SH, Levy MG. Identification of Pentatrichomonas hominis in felinefecal samples by polymerase chain reaction assay. Vet Parasitol; 2007;145,11-15.Levy MG, Litaker RW, Goldstein RJ, Dykstra MJ, Vandersea MW, Noga EJ. Piscinoodinium, a fishectoparasiticdinoflagellate, is a member of the class dinophyceae, subclass gymnodiniphycidae:convergent evolution with Amyloodinium. J Parasitol. 2007 Oct;93(5):1006-15.Levy MG, Poore MF, Colomi A, Noga EJ, Vandersea MW, Litaker RW. A highly specific PCR assay fordetecting the fish ectoparasite Amyloodinium ocellatum. Dis Aquat Organ. 2007 Jan 18;73(3):219-26.Stauffer SH, Birkenheuer AJ, Levy MG, Marr H, Gookin JL Evaluation of four DNAextraction methods for the detection of Tritrichomonas foetus in feline stool specimens by polymerasechain reaction. J Vet Diagn Invest 2007 In Press.Miller O, Fuller FJ, Gebreyes WA, Lewbart GA, Shchelkunov IS< Shivappa RB, Joiner C, Woolford G,Stone DM, Dixon PF, Raley ME, Levine JF. Phylogenetic analysis of spring viremia of carp virus revealsdistinct subgroups with common origins for recent isolates in North America and the UK. Dis AquatOrgan. 2007 Jul 16;76(3):193-204.Royal LW, Grafinger MS, Lascelles BD, Lewbart GA, Christian LS. Internal fixation of a femur fracturein an American bullfrog. J Am Vet Med Assoc. 2007 Apr 15;230(8):1201-4.Tuttle AD, Law JM, Harms CA, Lewbart GA, Harvey SB. Evaluation of the gross and histologicreactions to five commonly used suture materials in the skin of the African clawed frog (Xenopus laevis).J Am Assoc Lab Anim Sci. 2006 Nov;45(6):22-6.Willens S, Dupree SH, Stoskopf MK, Lewbart GA. Measurements of common iliac arterial blood flow inanurans using Doppler ultrasound. J Zoo Wildl Med. 2006 Jun;37(2):97-101.Lu W, Li L. Boosting method for nonlinear transformation models with censored survival data.Biostatistics. 2008 Mar 15.MacKillop E, Olby NJ, Linder KE, Brown TT. Intramedullary cavernous malformation of the spinal cord intwo dogs. Vet Pathol. 2007 Jul;44(4):528-32.MacKillop E, Thrall DE, Ranck RS, Linder KE, Munana KR. Imaging diagnosis--synchronous primary brain tumors in a dog. Vet Radiol Ultrasound. 2007Nov-Dec;48(6):550-3.Pfeiler TW, Lalush DS, Loboa EG. Semiautomated finite element mesh generation methods for a longbone.Comput Methods Programs Biomed. 2007 Mar;85(3):196-202.Sumanasinghe RD, Osborne JA, Loboa EG. Mesenchymal stem cell-seeded collagen matrices forbone repair: Effects of cyclic tensile strain, cell density, and media conditions on matrix contraction invitro. J Biomed Mater Res A. 2008 Mar 20.Wooten JG, Blikslager AT, Ryan KA, Marks SL, Law JM, Lascelles BD. Cyclooxygenaseexpression and prostanoid production in pyloric and duodenal mucosae in dogs after administration ofnonsteroidal anti-inflammatory drugs. Am J Vet Res 2008;69:457-64.Chorley BN, Crews AL, Li Y, Adler KB,Minnicozzi M, Martin LD. Differential Muc2 and Muc5acsecretion by stimulated guinea pig tracheal epithelial cells in vitro. Respir Res. 2006 Feb 25;7:35.Mexas AM, Hess RS, Hawkins EC, Martin LD. Pulmonary lesions in cats with diabetes mellitus. J VetIntern Med. 2006 Jan-Feb;20(1):47-51.Beale AB, Salmon J, Michau TM, Gilger BC. Effect of ophthalmic Nd:YAG laser energy on intraocularlenses after posterior capsulotomy in normal dog eyes. Vet Ophthalmol. 2006 Sep-Oct;9(5):335-40.Clode AB, Davis JL, Salmon J, Michau TM, Gilger BC. Evaluation of concentration of voriconazole inaqueous humor after topical and oral administration in horses. Am J Vet Res. 2006 Feb;67(2):296-301.Jackson E, Anderson K, Ashwell C, Petitte J, Mozdziak PE. CA125 expression in spontaneous ovarianadenocarcinomas from laying hens. Gynecol Oncol. 2007Jan;104(1):192-8.Mozdziak PE, Wu Q, Bradford JM, Pardue SL, Borwornpiny S, Giamario C, Petitte JN. Identification ofthe lacZ insertion site and beta-galactosidase expression in transgenic chickens. Cell Tissue Res. 2006Apr;324(1):41-53.Mozdziak PE, Wysocki R, Angerman-Stewart J, Pardue SL, Petitte JN. Production of chick germlinechimeras from fluorescence-activated cell-sorted gonocytes. Poult Sci. 2006 Oct;85(10):1764-8.80

Mozdziak,Paul (PE)Muddiman,David (DC)Muddiman,David (DC)Muddiman,David (DC)Muddiman,David (DC)Muddiman,David (DC)Muddiman,David (DC)Muddiman,David (DC)Muddiman,David (DC)Muddiman,David (DC)Muddiman,David (DC)Muddiman,David (DC)Muddiman,David (DC)Muddiman,David (DC)Muddiman,David (DC)Muddiman,David (DC)Muddiman,David (DC)Muddiman,David (DC)Petitte JN, Mozdziak PE. The incredible, edible, and therapeutic egg. Proc Natl Acad Sci U S A. 2007Feb 6;104(6):1739-40.Caskey DC, Yamamoto T, Addicott C, Shoemaker RK, Vacek J, Hawkridge AM,Muddiman DC, Kottas GS, Michl J, Stang PJ. Coordination-driven face-directedself-assembly of trigonal prisms. Face-based conformational chirality. J Am Chem Soc.2008 Jun 18;130(24):7620-8.Collier TS, Hawkridge AM, Georgianna DR, Payne GA, Muddiman DC. Top-down identification andquantification of stable isotope labeled proteins from Aspergillus flavus using online nano-flow reversedphaseliquid chromatography coupled to a LTQ-FTICR mass spectrometer. Anal Chem. 2008 Jul1;80(13):4994-5001.Dixon RB, Bereman MS, Muddiman DC, Hawkridge AM. Remote mass spectrometric sampling ofelectrospray- and desorption electrospray-generated ions using an air ejector. J Am Soc Mass Spectrom.2007 Oct;18(10):1844-7.Dixon RB, Muddiman DC, Hawkridge AM, Fedorov AG. Probing the mechanisms of an air amplifierusing a LTQ-FT-ICR-MS and fluorescence spectroscopy. Am Soc Mass Spectrom. 2007Nov;18(11):1909-13.Dixon RB, Sampson JS, Hawkridge AM, Muddiman DC. Ambient aerodynamic ionization source forremote analyte sampling and mass spectrometric analysis. Anal Chem. 2008 Jul 1;80(13):5266-71.Georgianna DR, Hawkridge AM, Muddiman DC, Payne GA. Temperature-Dependent Regulation ofProteins in Aspergillus flavus: Whole Organism Stable Isotope Labeling by Amino Acids. J ProteomeRes. 2008 Jul;7(7):2973-9.Hawkridge AM, Heublein DM Bergen HR 3rd, Cataliotti A, Burnett JC Jr, Muddiman DC. Quantitativemass spectral evidence for the absence of circulating brain natriuretic peptide(BNP-32) in severe human heart failure. Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17442-7.Hawkridge AM, Muddiman DC, Hebulein DM, Cataliotti A< Burnett JC Jr. Effect of plasma proteindepletion on BNP-32 recovery. Clin Chem. 2008 May;54(5):933-4.Kang S, Hawkridge AM, Johson KL, Muddiman DC, Prevelige PE Jr. Identification of subunit-subunitinteractions in bacteriophage P22 procapsids by chemical cross-linking and mass spectrometry. JProteome Res. 2006 Feb;5(2):370-7.Sampson JS, Hawkridge AM, Muddiman DC. Direct characterization of intact polypeptidesby matrix-assisted laser desorption electrospray ionization quadrupole Fourier transform ion cyclotronresonance mass spectrometry. Rapid Commun Mass Spectrom.2007;21(7):1150-4.Sampson JS, Hawkridge AM, Muddiman DC. Generation and detection of multiply-charged peptidesand proteins by matrix-assisted laser desorption electrospray ionization (MALDESI) Fourier transform ioncyclotron resonance mass spectrometry. J Am Soc Mass Spectrom. 2006 Dec;17(12):1712-6.Williams DK Jr, Hawkridge AM, Muddiman DC. Sub parts-per-million mass measurement accuracy ofintact proteins and product ions achieved using a dual electrospray ionization quadrupole fouriertransform ion cyclotron resonance mass spectrometer. J Am Soc Mass Spectrom. 2007 Jan;18(1):1-7.Williams DK Jr, Meadows CW, Bori ID, Hawkridge AM Comins DL, Muddiman DC. Synthesis,characterization, and application of iodoacetamide derivatives utilized for the ALiPHAT strategy. J AmChem Soc. 2008 Feb 20;130(7):2122-3.Yang HB, Das N, Huang F, Hawkridge AM, Diaz DD, Arif AM Finn MG, Muddiman DC,Stang PJ. Incorporation of 2,6-di(4,4'-dipyridyl)-9-thiabicyclo[3.3.1]nonane into discrete 2Dsupramolecules via coordination-driven self-assembly.J Org Chem. 2006 Aug 18;71(17):6644-7.Yang HB, Das N, Huang F, Hawkridge AM, Muddiman DC, Stang PJ. Molecular architecture viacoordination: self-assembly of nanoscale hexagonal metallodendrimers with designed building blocks. JAm Chem Soc. 2006 Aug 9;128(31):10014-5.Yang HB, Hawkridge AM, Haung SD, Das N, Bunge SD, Muddiman DC, Stang PJ. Coordination-drivenself-assembly of metallodendrimers possessing well-defined and controllable cavities as cores. J AmChem Soc. 2007 Feb 21;129(7):2120-9.Yang P, Cooks RG, Ouyang Z, Hawkridge AM, Muddiman DC. Gentle protein ionization assisted byhigh-velocity gas flow. Anal Chem. 2005 Oct 1;77(19):6174-83.81

Munana,Karen (KR)Nascone-Yoder,NanetteNoga, Ed (EJ)Noga, Ed (EJ)Nordone,Shila (SK)Odle, JackOdle, JackOdle, JackOlby, Natasha(NJ)Olby, Natasha(NJ)Olivry, ThierryOlivry, ThierryOlivry, ThierryOlivry, ThierryOlivry, ThierryOlivry, ThierryOsborne,Jason (JA)Osborne,Jason (JA)MacKillop E, Thrall DE, Ranck RS, Linder KE, Munana KR. Imaging diagnosis--synchronous primary brain tumors in a dog. Vet Radiol Ultrasound. 2007Nov-Dec;48(6):550-3.Lipscomb K, Schmitt C, Sablyak A, Yoder JA, Nascone-Yoder N. Role for retinoid signaling in left-rightasymmetric digestive organ morphogenesis. Dev Dyn. 2006 Aug;235(8):2266-75.Levy MG, Litaker RW, Goldstein RJ, Dykstra MJ, Vandersea MW, Noga EJ. Piscinoodinium, a fishectoparasiticdinoflagellate, is a member of the class dinophyceae, subclass gymnodiniphycidae:convergent evolution with Amyloodinium. J Parasitol. 2007 Oct;93(5):1006-15.Levy MG, Poore MF, Colomi A, Noga EJ, Vandersea MW, Litaker RW. A highly specific PCR assay fordetecting the fish ectoparasite Amyloodinium ocellatum. Dis Aquat Organ. 2007 Jan 18;73(3):219-26.Nordone SK, Ignacio GA, Su L, Sempowski GD, Golenbock DT, Li L, Dean GA. Failure of TLR4-drivenNF-kappa B activation to stimulate virus replication in models of HIV type 1 activation. AIDS Res HumRetroviruses. 2007 Nov;23(11):1387-95.Blikslager AT, Moeser AJ, Gookin JL, Jones SL, Odle J. Restoration of barrier functionin injured intestinal mucosa. Physiological Reviews 2007; 545-564.Corl BA, Odle J, Niu X, Moeser AJ, Gatlin LA, Phillips OT, Blikslager AT, Rhoads JM.Arginine activates intestinal p70(S6k) and protein synthesis in piglet rotavirus enteritis. J Nutr2008;138:24-9Rhoads JM, Corl BA, Harrell R, Niu X, Gatlin L, Phillips O, Blikslager AT, Moeser A, Wu G,Odle J. Intestinal ribosomal p70(S6K) signaling is increased in piglet rotavirus enteritis.Am J Physiol Gastrointest Liver Physiol 2007;292:G913-22.MacKillop E, Olby NJ, Linder KE, Brown TT. Intramedullary cavernous malformation of the spinal cord intwo dogs. Vet Pathol. 2007 Jul;44(4):528-32.Pease A, Sullivan S, Olby N, Galano H, Cerda-Gonzalez S, Robertson ID, Gavin P, Thrall D. Value of asingle-shot turbo spin-echo pulse sequence for assessing the architecture of the subarachnoid spaceand the constitutive nature of cerebrospinal fluid. Vet Radiol Ultrasound. 2006 May-Jun;47(3):254-9Olivry T, Dunston SM, Pluchino K, Porter K, Hammberberg B. Lack of detection of circulating skinspecificIgE autoantibodies in dogs with moderate or severe atopic dermatitis.Vet ImmunolImmunopathol. 2008 Mar 15;122(1-2):182-7.Olivry T, LaVoy A, Dunston SM, Brown RS, Lennon EM, Warren SJ, Prisayanh P, Muller EJ, Suter MM,Dean GA. Desmoglein-1 is a minor autoantigen in dogs with pemphigus foliaceus. Vet ImmunolImmunopathol. 2006 Apr 15;110(3-4):245-55.Olivry T, Mueller R, Nuttall T, Favrot C, Prelaud P, International Task Force on Canine Atopic Dermatitis.Collaborators: Bensignor E, Carlotti D, DeBeor D, Favrot C, Griffin C, Halliwell R, Hammerberg B, Hill P,Iwasaki T, Jackson H, Maeda S, Masuda R, Mueller R, Nuttall T, Olivry T, Prelaud P, Sousa C, WillemseT. Determination of CADESI-03 thresholds for increasing severity levels of canine atopic dermatitis. VetDermatol. 2008 Jun;19(3):115-9.Pucheu-Haston CM, Jackson HA, Olivry T, Dunston SM, Hammerberg B. Epicutaneous sensitizationwith Dermatophagoides farinae induces generalized allergic dermatitis and elevated mite-specificimmunoglobulin E levels in a canine model of atopic dermatitis. Clin Exp Allergy. 2008 Apr;38(4):667-79.Pucheu-Haston CM, Shuster D, Olivry T, Brianceau P, Lockwood P, McClanahan T, de Waal Malefyt R.Mattson JD, Hammerberg B. A canine model of cutaneous late-phase reactions: prednisolone inhibitionof cellular and cytokine responses. Immunology. 2006Feb;117(2):177-87.Yearley JH, Stanton C, Olivry T, Dean GA. Phagocytic plasmacytoma in a dog. Vet Clin Pathol. 2007Sep;36(3):293-6.Parker J, Oviedo-Rondon EO, Clack BA, Clemente-Hernandez S, Osborne J, Remus JC, Kettunen H,Makivuolkko H, Pierson EM. Enzymes as feed additive to aid in responses against Eimeria species incoccidia-vaccinated broilers fed corn-soybean meal diets with different protein levels. Poult Sci. 2007Apr;86(4):643-53.Sumanasinghe RD, Osborne JA, Loboa EG. Mesenchymal stem cell-seeded collagen matrices forbone repair: Effects of cyclic tensile strain, cell density, and media conditions on matrix contraction invitro. J Biomed Mater Res A. 2008 Mar 20.82

Oviedo-Rondon,Edgar (EO)Petitte, Jim(JN)Petitte, Jim(JN)Petitte, Jim(JN)Petitte, Jim(JN)Petters, Bob(RM)Petters, Bob(RM)Petters, Bob(RM)Piedrahita,JorgePiedrahita,JorgePiedrahita,JorgePiedrahita,Jorge (JA)Rodriguez-Puebla,MarceloRodriguez-Puebla,MarceloSherry, BarbStoskopf,Michael (MK)Stoskopf,Michael (MK)Stoskopf,Michael (MK)Stoskopf,Michael (MK)Parker J, Oviedo-Rondon EO, Clack BA, Clemente-Hernandez S, Osborne J, Remus JC, Kettunen H,Makivuolkko H, Pierson EM. Enzymes as feed additive to aid in responses against Eimeria species incoccidia-vaccinated broilers fed corn-soybean meal diets with different protein levels. Poult Sci. 2007Apr;86(4):643-53.Jackson E, Anderson K, Ashwell C, Petitte J, Mozdziak PE. CA125 expression in spontaneous ovarianadenocarcinomas from laying hens. Gynecol Oncol. 2007Jan;104(1):192-8.Mozdziak PE, Wu Q, Bradford JM, Pardue SL, Borwornpiny S, Giamario C, Petitte JN. Identification ofthe lacZ insertion site and beta-galactosidase expression in transgenic chickens. Cell Tissue Res. 2006Apr;324(1):41-53.Mozdziak PE, Wysocki R, Angerman-Stewart J, Pardue SL, Petitte JN. Production of chick germlinechimeras from fluorescence-activated cell-sorted gonocytes. Poult Sci. 2006 Oct;85(10):1764-8.Petitte JN, Mozdziak PE. The incredible, edible, and therapeutic egg. Proc Natl Acad Sci U S A. 2007Feb 6;104(6):1739-40.Estrada JL, Collins B, York A, Bischoff SR, Sommer J, Tsai S, Petters RM, Piedrahita JA.2008. Successful cloning of the Yucatan minipig using commercial/occidental breeds as oocyte donorsand embryo recipients. Cloning and Stem Cells. 10:287-296.Estrada JL, Sommer J, Collins B, Mir B, Martin A, York A, Petters RM, and Piedrahita JA2007. Swine generated by somatic cell nuclear transfer have increased incidence of intra uterine growthrestriction (IUGR). Cloning and Stem Cells 9:229-236.Ng YF, Chan HH, Chu PH, To CH, Gilger BC, Petters RM, Wong F. Multifocalelectroretinogram in rhodopsin P347L transgenic pigs. Invest Ophthalmol Vis Sci. 2008 May;49(5):2208-15.Estrada JL, Collins B, York A, Bischoff SR, Sommer J, Tsai S, Petters RM, Piedrahita JA.2008. Successful cloning of the Yucatan minipig using commercial/occidental breeds as oocyte donorsand embryo recipients. Cloning and Stem Cells. 10:287-296.Estrada JL, Sommer J, Collins B, Mir B, Martin A, York A, Petters RM, and Piedrahita JA2007. Swine generated by somatic cell nuclear transfer have increased incidence of intra uterine growthrestriction (IUGR). Cloning and Stem Cells 9:229-236.Zaunbrecher G, Mir B, Dunne PW, Breen M, Piedrahita JA. 2008. Enhancement of extrachromosomal recombination in somatic cells by affecting the ratio of homologous recombination (HR) tonon-homologous end joining (NHEJ). Animal Biotechnology 19:6-21.Farin PW, Piedrahita JA, Farin CE. Errors in development of fetuses and placentas from in vitroproducedbovine embryos.Theriogenology. 2006 Jan 7;65(1):178-91.Macias E, Kim Y, Miliani de Marval PL, Klein-Szanto A, Rodriguez-Puebla ML. (2007)Cdk2 deficiency decreases ras/CDK4-dependent malignant progression, but not myc-inducedtumorigenesis. Cancer Res. 67(20):9713-20Marcias E, de Marval PL, Senderowicz A, Cullen J, Rodriguez-Puebla, ML. Expression of CDK4 orCDK2 in mouse oral cavity is retained in adult pituitary with distinct effects on tumorigenesis. CancerRes. 2008 Jan 1;68(1):162-71.Zurney, J., K.E. Howard, and B. Sherry. 2007. Basal expression of IFNAR and Jak-STATcomponents are determinants of cell type-specific differences in the cardiac antiviral response. Journalof Virology, 81:13668-13680.Acton AE, Beale AB, Gilger BC, Stoskopf MK. Sustained release cyclosporine therapy for bilateralkeratoconjunctivitis sicca in a red wolf (Canis rufus). Invest Ophthalmol Vis Sci. 2007 May;48(5):2023-9.Birkenheuer AJ, Harms CA, Neel J, Marr HS, Tucker MD, Acton AE, Tottle AD, Stoskopf MK. Theidentification of a genetically unique piroplasma in North American river otters (Lontra canadensis).Parasitology. 2007 may;134(Pt5):631-5.Gustafson L, Showers W, Kak T, Levine J, Stoskopf M. Temporal and spatial variability in stableisotope compositions of a freshwater mussel: implications for biomonitoring and ecological studies.Oecologia. 2007 May;152(1):140-50.Henson-Ramsey H, Kennedy-Stoskopf S, Levine JF, Shea D, Talylor SK, Stoskopf MK. A comparisonof two exposure systems to apply malathion to Lumbricus terrestris L. Bull Environ Contam Toxicol. 2007Jun;78(6):427-31. Epub 2007 Jul 7.83

Vaden, Shelly(SL)Vaden, Shelly(SL)Vaden, Shelly(SL)Williams,LaurelYoder, Jeff(JA)Yoder, Jeff(JA)Yoder, Jeff(JA)Zhang,DaowenZhang,DaowenHill TL, Breitschwerdt EB, Cecere T, Vaden S. Concurrent hepatic copper toxicosis and Fanconi'ssyndrome in a dog. J Vet Intern Med. 2008 Jan-Feb;22(1):219-22Puskar M, Lemons C, Papich MG, Vaden SL, Birkenheuer A. Antibiotic-resistant Corynebacteriumjeikeium urinary tract infection in a cat. J Am Anim Hosp Assoc. 2007 Jan-Feb;43(1):61-4.Vaden SL, Levine JF, Lees GE, Groman RP, Grauer GF, Forrester SD. Renal biopsy: a retrospectivestudy of methods and complications in 283 dogs and 65 cats. J Vet Intern Med. 2005 Nov-Dec;19(6):794-801.Duncan AW, Marr HS, Birkenheuer AJ, Maggi RG, Williams LE, Correa MT, Breitschwerdt EB.Bartonella DNA in the blood and lymph nodes of Golden Retrievers with lymphoma and in healthycontrols. Vet Intern Med. 2008 Jan-Feb;22(1):89-95.Deiters A, Yoder JA. 2006. Conditional transgene and gene targeting methodologiesin zebrafish. Zebrafish. 3: 415-429Lipscomb K, Schmitt C, Sablyak A, Yoder JA, Nascone-Yoder N. Role for retinoid signaling in left-rightasymmetric digestive organ morphogenesis. Dev Dyn. 2006 Aug;235(8):2266-75.Young DD, Lusic H, Lively MO, Yoder JA, Deiters A. 2008. Gene Silencing with Light-ActivatedAntisense Agents. Submitted.Lin J, Zhang D, Davidian M. Smoothing spline-based score tests for proportional hazards models.Biometrics. 2006 Sep;62(3):803-12Tzeng JY, Zhang D. Haplotype-based association analysis via variance-components score test. Am JHum Genet. 2007 Nov;81(5):927-38.85

1The Center for Comparative Medicine and Translational Researchresearch,full circle.research,full circle.many CCMTR, species,one medicine. OneMedicineMarketingNorth Carolina State University College of Veterinary Medicine 4700 Hillsborough Street Raleigh, NC 27606 P 919.515.8113 F 919.515.3044 www.ncsu.edu/ccmtr 86

Center for Comparative Medicine and Translational ResearchCCMTR NewsMarch 31, 2008Volume 2 Issue 1Innovation Grants AwardedOn December 5, 2007 a request for Innovation Grant proposals went to all members via the e-mail. Thepurpose of this grant program was to support proposals that advance the objectives of the CCMTR. Theproposals that would benefit multiple investigators, promote of basic/clinical investigator interactions,and/or provide critical resources for submission of extramural, multi-investigator proposals wereconsidered responsive to the RFP.Recipient Grants include:Upgrade of Compound Microscope Leica DM5000B and PC Workstation (Yoder)Expansion of Flow Cytometry and Cell Sorting Laboratory Service Core (Tompkins, Dean)Determining the Mechanism of Action of a Novel Small Molecule with Unique Teratogenic andMelanogenic Properties (Nascone-Yoder, Hauck, Deiters)Canine B cell Lyphomas: Histopathologic, Cytologic, Flow Cytometric, Cytogenic, andMolecular Characterization (Suter, Breen, Tompkins, Neel, Matthew, Lascelles, Cullen,Ruslander, Valli, Vernau)Highlighted Research – Dr. Char FarinDr. Charlotte Farin, a member of the clinical genomics core, is a newly appointed at-large member of theexecutive committee. She is currently a professor in the Department of Animals Science (CALS).Dr. Farin’s research covers two main related areas; examination of the effects of invitro embryo production (IVP) systems on fetal development and gene expression incattle; and the evaluation of mechanisms regulating in vitro maturation ofmammalian oocytes.Working in collaboration with Dr. Peter Farin, also a clinical genomics coremember, Drs Farin and Farin have demonstrated that production of embryos usingthe embryo production in vitro systems can be associated with the abnormal fetaland placental development. In this work, their laboratories have assessed the effectsof IVP on expression of mRNAs for the insulin-like growth factor family, a group of ligands, receptors andassociated proteins that play an important role in regulating normal fetal and post-natal development. Thisgrowth factor family includes genes that are imprinted (Igf2 and Igf2r) or non-imprinted (Igf1, Igf1r).Their data suggest that abnormalities in fetal growth associated with IVP reflect dysregulation of not onlyimprinted but also non-imprinted genes. Most recently, working in collaboration with Dr. JorgePiedrahita's laboratory, their group has documented the existence of an antisense noncoding (nc) RNA tothe Igf2r gene in cattle (bovine AIR, antisense to Igf2R). The murine homolog of this ncRNA has beenimplicated in regulation of imprinted expression of Igf2r in mice. Expression of bovine AIR ncRNA wasshown to vary with stage of fetal development as well as with method of embryo production (in vivo vs. invitro).The second major area of Dr. Char Farin’s research program is the examination of mechanisms regulatingin vitro maturation of mammalian oocytes. In cattle, in vitro embryo production involves maturation ofoocytes obtained from donor females. When oocytes are matured in vitro, however, their developmentalcompetency is compromised. Understanding factors that regulate in vitro oocyte maturation is importantfor improving the efficiency of current IVP practices. Work in Farin’s laboratory focuses on the use ofspecific transcriptional inhibitors to study follicle stimulating hormone-induced resumption of meiosis incultured mammalian oocytes. The lab has successfully used approaches for gene expression profiling(mice: serial analysis of gene expression; cattle: differential display) to identify candidate genes involved inregulating the resumption of oocyte meiotic maturation in vitro. They have also used short interferingRNA approaches to disrupt candidate mRNA expression to verify the physiological functions of the89

candidate genes with respect to their ability to regulate the initiation of oocyte meiosis.Novartis Gift to the CenterThe Center of Comparative Medicine and Translational Research is the recipient of a $625,000 gift fromNorvartis Animal Health US, Inc., to help support the Clinical Trials Program.Presented over a five-year period, the Novartis gift will fund a clinical trials veterinarian, a veterinaryresearch technician, and laboratory space and equipment that will be dedicated to supporting clinicalresearch studies involving patients in the CVM Veterinary Teaching Hospital.“Clinical studies are integral to the advancement of veterinary medicine,” says Dr. Gregg Dean, director ofthe Center. “Such studies investigate risk factors for disease as well as methods to prevent, treat, or cureillnesses that affect both animals and humans. The Norvartis gift will fund resources that are critical tohelping the CCMTR ensure an effective Clinical Trials Program.”Dean says the CCMTR Clinical Trials Program (CTP) enables clinical investigators the opportunity toevaluate novel approaches to diagnose and treat disease and deliver innovative solutions that enhanceanimal and human health. The CTP promotes research collaboration by serving as a liaison betweenclinical investigators, basic researchers, referring veterinarians, pet owners, and industry scientists. Inaddition, participating in the program may help interest DVM students and residents in exploring careers intranslational medicine.The CTP can assist with or independently design and implement all organizational and technical aspects ofclinical trials including case recruitment, patient enrollment, patient visits, sample collection andprocessing, and patient follow-up and data analysis. There are currently 19 ongoing investigations in sevenhospital clinics: Cardiology, Dermatology, Internal Medicine, Neurology, Oncology, Pain Management,and Surgery.According to Dean, a dedicated clinical trials enterprise is an essential component of an evidence-basedmedicine approach to determine the standard of care. Such trials, he says, enable clinical investigators todetermine the best way to treat specific medical conditions while offering patients access to the mostadvanced diagnostic and therapeutic technology available.“It’s critical for the CVM to play a leading role in performing well-controlled trials designed to advance thequality of patient care,” says Dean. “The Novartis support will allow us to continue to build a clinical trialframework that will become self supporting as it matures into a premiere national veterinary clinical trialsprogram. We envision that the CTP will also conduct trials that will have implications for the treatment ofpeople, making the program unique in the veterinary and human medical fields.”Flow Cytometry Service Core Expands ServiceThe NCSU Flow Cytometry and Cell Sorting Laboratory Service Core, located on the third floor of theCollege of Veterinary Medicine main building, is expanding its services.The laboratory currently provides instrumentation and assistance for multi-parameter flow cytometricanalysis and sorting. The laboratory operates as a by-appointment, fee-for-service laboratory.Dr. Mary Tompkins is the Director of the Core and Ms. Janet Dow is the supervisor who oversees the dayto-dayoperation. In the past, the laboratory consisted of only three flow cytometers. Two Becton-Dickinson instruments which are used for analysis only, including a three-color capability FACScan and afour-color capability FACScalibur. The third, a Beckman Coulter MoFlo is a state-of-the-art, high speedcell sorter, equipped with three lasers and 10-color capability.One of the instruments to be added to the core includes the Xenogen Lumina in vivo imaging system. Thisinstrument is designed for detection of fluorescence or luminescence in live animals (mice, rats, piglets).The second instrument is a Becton-Dickinson LSRII analytical flow cytometer currently equipped with twolasers (488nm and 633 nm) providing 6 color capability. This is a state-of-the-art fiber-optic, digital90

instrument. Through our recent Innovation Grants, the LSRII has been upgraded in order to increase theservices available in the Flow Cytometry and Cell Sorting Service Core. A third Violet laser (20mW,405nm) and the necessary photomultiplier tubes and filter sets required to provide up to 3 additional colorshave been added.This upgrade now allows for cutting edge flow cytometry that requires the analysis of very small, raresamples and/or very specifically defined cell types identified by multiple cell surface molecules. For eitherapplication, many colors are needed.These two additional pieces of equipment will be housed in room 257 of the CVM Research Building.There is a plan to add a part-time technician.Future plans for expansion include the possibility of offering new services such as custom conjugation ofantibodies. This would be particularly useful in the CVM environment where few directly-conjugatedantibodies are available for veterinary species.Pilot Grant Research-in-Progress SymposiumThe Pilot Grant Research-in-Progress Symposium will be held on May 15, 2008. This year the symposiumwill held at The Dorothy and Roy Park Alumni Center on Centennial Campus. The symposium isscheduled to begin at 1 p.m. with the eight recipients of the pilot project grants presenting their research.The symposium will be followed by a reception. Reservations will be required. Information regarding thereservation process will be circulated via e-mail.91

CVM News & Media8/15/08 1:55 PMCalendar | Map | People | SearchMainDr. Thakur Recipient of USDA GrantDr. Siddhartha Thakur, assistant professor of swine health and reproductionin the Department of Population Health and Pathobiology, has received athree-year, $592,000 grant from the U.S. Department of Agriculture (USDA)to study the occurrence of Salmonella in pigs that haven't been given antimicrobialdrugs either for treatment or growth promotion.Dr. Thakur, a member of the Center for Comparative Medicine andTranslational Research, will take samples from pig populations, theirenvironments, and pork processing plants to determine the strains of theSalmonella pathogen that these pigs may be exposed to, as well as the rateof infection in these environments.Anti-microbial free pigs, or ABF pigs, haven't been given anti-microbialtreatments that speed growth and kill certain pathogens. Pork producers areincreasing their stock of ABF pigs in response to increasing demand fromconsumers for "naturally grown" pork. Some of the ABF pig farms also raisetheir pigs outdoors instead of in barns, which can open new avenues forpossible Salmonella contamination."Salmonella is responsible for most of the bacterial food-borne illnesses inthe U.S.," Dr. Thakur says. "It affects up to an estimated 1.5 million peopleper year in this country alone, so it's vital that we protect our food supplyfrom Salmonella contamination."The grant is part of the USDA's National Integrated Food Safety Initiative. Dr.Thakur and colleague Dr. W.E. Morgan Morrow, an animal science professorin the College of Agriculture and Life Sciences, believe that the informationfrom the study will both help protect the general population from food-borneillness, and enable pork producers to better prevent and control outbreaks."It will be a win-win situation for the farmers of North Carolina, who willreceive information vital to the health of their farm animals, and for theconsumers who can be certain that their food supply is safe," Dr. Thakursays.Posted May 21, 2008--Tracey PeakeNC State College of Veterinary MedicineNews & Media4700 Hillsborough StreetRaleigh, NC 27606http://webapps.cvm.ncsu.edu/news/view.cfm?id=86092Page 1 of 1

Hens’ Histories Hint at Ovarian Cancer Biomarker8/15/08 1:54 PMABOUT CONTACT PDF PAST ISSUES RESEARCH AND GRADUATE STUDIESbackHens’ Histories Hint atOvarian CancerBiomarkerRather than ponder the ages-old question of the chicken andthe egg, a group of NC State researchers is using egg-layingchickens and systems biology to answer a more pressingissue: What comes first, ovarian cancer or detectablephysiological changes related to the cancer?“If we can find a true biomarker, we willbe able to save countless lives.”Ovarian cancer is particularly deadly, with less than half of thewomen contracting it surviving five years. “It’s such a horribledisease, and it’s usually diagnosed too late,” says Dr. JonHorowitz, associate professor of molecular biomedicalsciences in the College of Veterinary Medicine (CVM). Thebelated diagnosis means scientists don’t know if there are anytelltale signs, or biomarkers, in a woman’s physiology thatcould serve as an early warning, similar to the increase inprostate-specific antigen (PSA) in men that signals thepotential for prostate cancer.Blood work collected by Dr. Jim Petitte fromscores of hens gives scientists a look atphysiological changes as they develop ovariancancer.Researchers at the Mayo Clinic in Minnesota began collectingblood samples from every female patient several years agoand have, over time, amassed more than 100 samples fromwomen with early-stage ovarian cancer. But the samplesprovide only a single snapshot for each woman, says Dr. DaveMuddiman, who formerly worked at the Mayo Clinic and nowheads up the W.M. Keck FT-ICR Mass SpectrometryLaboratory in the College of Physical and MathematicalSciences at NC State. That makes it difficult to identify anypotential biomarkers.Through the CVM’s Center for Comparative Medicine andTranslational Research, which links human and animalresearch efforts across NC State, Muddiman joined forces withHorowitz and poultry science professors Jim Petitte, PaulMozdziak, and Ken Anderson. Because 10 to 25 percent ofhens develop ovarian cancer after about two years of steadyegg production, the poultry science group has collected bloodsamples and other data on about 250 hens before and aftertheir cancers. That data can be beneficial to studying humancancer, Petitte says, because of similarities between chickenand human cells. “We have what amounts to a medical historyon these hens,” Muddiman says, “We can see how theirsystems changed over time.”Muddiman’s research team is running extensive tests on theDrs. Dave Muddiman (left) and Jon Horowitz willconduct an in-depth analysis of the hen bloodsamples for clues that could lead to a diagnostictest for ovarian cancer.http://www.ncsu.edu/research/results/vol7n2/07.html93Page 1 of 2

Hens’ Histories Hint at Ovarian Cancer Biomarker8/15/08 1:54 PMhen blood samples to catalog molecular changes. Once theyfind some potential targets, Horowitz will conduct a more indepthprotein and genetic analysis. He will also compare thefindings with the human samples at the Mayo Clinic to see if acommon biomarker can be found. “We have to figure outwhich molecular changes are real and which are red herrings,”he says. “If we can find a true biomarker, we will be able tosave countless lives.”Results: Research and Graduate Studies at North Carolina State Universityhttp://www.ncsu.edu/research/results/vol7n2/07.html94Page 2 of 2

1The Center for Comparative Medicine and Translational ResearchNews Release – August 6, 2007Budget Researchers and Create Accounting Chemical ‘Lightresources,solutions.Switches’ to Aid Study of Gene Functionmany species,one medicine.CCMTR NCSU College of Veterinary Medicine 4700 Hillsborough Street Raleigh, NC 27606 P 919.515.8113 F 919.515.3044 www.ncsu.edu/ccmtr95

Budget and AccountingThe initial commitment to the CCMTR from Dean Arden and the CMV was for$100,000 per year for 5 years. We are currently in year 3 of that commitment. Inaddition, Dean Arden secured up to 3 FTE for advancement of the CCMTR. Thefirst FTE is occupied by the director. The second FTE (available 2007-2008)went unfilled for 2007-2008 and funds from this position were used to expandCenter grant programs. This FTE will be filled by the Clinical Studies CoreVeterinarian in the near future. It is unclear whether or when the third FTE will beavailable. In addition, the CVM has provided an administrative assistant for theCenter. Other sources of funds have come from CVM departments and from theCollege of Agriculture and Life Sciences. The Vice Chancellor of Research andGraduate Studies has provided matching funds for the training program.Extramural sources of revenue are just coming online from NIH/NCRR (T32training grant), Novartis Animal Health (to support clinical trials effort), and theNIH/NCRR Clinical and Translational Sciences Award (CTSA) through UNC-Ch.Thus far, only the Clinical Studies Core has generated service revenue thatcomes directly to the Center.The accounting for the Center has been provided by Ms. Greta Johansen andMr. Barry Bright in the CVM. Purchasing has also been managed by the CVM.A synopsis of the revenue and expenditures for the last three years follows.96

Budget OverviewFunding AvailableFunding AsExpended:Fiscal Year 2006:Total Salaries -Total Staff Benefits 386Total Operating 36,409Total Fiscal Year 06: 100,000 36,795College State Funding 100,000Fiscal Year 2007:Total Salaries 83,305Total Staff Benefits 18,869Total Operating 132,742Total Fiscal Year 07: 234,915 234,915College State Funding 234,915Fiscal Year 2008:Total Salaries 200,359Total Staff Benefits 38,329Total Operating 173,426Total Fiscal Year 08: *Note 501,534 412,113College State Funding 421,534Vice Chancellor Funding 80,000501,534Fiscal Year 2009:Total SalariesStaff Benefits - been centralizedTotal OperatingTotal Fiscal Year 09: 774,064College State Funding 440,112Vice Chancellor Funding 80,000Novartis Animal Health Funding 125,000NIH Grant Funding 128,952774,06497

1The Center for Comparative Medicine and Translational Researchresearch,full circle.research,full circle.many Growing, species,one Improving medicine.Self EvaluationNorth Carolina State University College of Veterinary Medicine 4700 Hillsborough Street Raleigh, NC 27606 P 919.515.8113 F 919.515.3044 www.ncsu.edu/ccmtr 98

NCSU Center for Comparative Medicine & Translational ResearchAllergy Core Self-EvaluationThierry Olivry, DrVet, PhD, DipACVD, DipECVDAllergy Core LeaderOverviewAt the time of its inception, the allergy core was composed of four clinicians (twodermatologists, one small animal internist, one equine internist) and two “basic science”researchers (one immunologist, one immunoparasitologist). At the middle of 2008, afterthe departure of two faculty and lack of interest of another, the core is only composed ofone dermatologist (Thierry Olivry) and the two original researchers (Gregg Dean andBruce Hammerberg). The current vision for this core is the development of allergenindependentimmunotherapy in dogs with allergic skin and/or gastrointestinal diseases.AccomplishmentsIn spite of the small number of core members, two accomplishments are worth noticing.1. Obtention of major funding for supporting a colony of allergic dogs.In 2005, we obtained a nearly $500K grant from a Japanese federal institute of allergyresearch for supporting a colony of maltese-beagle atopic dogs and test a noveladjuvanted allergen-specific immunotherapy for Japanese cedar pollen allergy. Asecond grand of $260K was received in 2007 for a pilot study on sublingualimmunotherapy using Japanese cedar pollen allergens in fusion protein form. We havebegun working on budgeting for a larger trial on sublingual immunotherapy for 2009-2011 sponsored by the same Japanese center. In 2007, the study involved work done inthe laboratories of all three allergy core members.This set of studies embodies the spirit of the center: a translation from in vitro lab workto mouse studies to a trial involving dogs as a proof-of-concept study before furtherdevelopment can be done in humans. If the studies are successful, the concepts will bedeveloped as well for canine allergy treatment.2. Submission of an R21 grant to NIHIn November 2007, all three group members submitted an R21 grant proposal to NIH totest the effect of probiotics in dogs with food allergy. This study had three arms, each ofthem under the responsibility of a different core member: in vitro testing of Lactobacillusstrains (Gregg Dean), followed by testing of the bacteria using gut explants (BruceHammerberg) then followed by a pilot study using our allergic dog model (ThierryOlivry). This project was not funded.3. Submission of a collaborative grant proposal to SBIR.In December 2007, we participated to the submission of an SBIR grant proposal fromSyntrix biosystems to NIH to perform a large randomized controlled trial to test theefficacy of aminopterin for canine atopic dermatitis. This is in follow-up of a small pilotstudy performed at the CVM by group members in 2005. The grant has been funded,and we expect the trial to be administered, in part, by the Clinical Study Core of the99

center. The trial is likely to commence in January 2009.ChallengesWe believe that there are two challenges that are impediments to the furtherdevelopment of our core: small number of participants and time.This core currently has three members, and each of us is occupied completing projectsthat are mostly individual. Collaboration still does exist as two of the members(Hammerberg and Olivry) share the same lab, and there is a crosstalk between this laband Gregg Dean’s team. Some experiments and runs are done in one lab or the other.We have a vision of accomplishment of a common project using the expertise of each ofus, but time is lacking to take this on to the next level (see below).Future goalsWe would like to perform at least a large study to design and test a probiotic approachfor treatment of canine skin and gastrointestinal allergy. The approach would be similarto that proposed – unsuccessfully – to the R21. Alternatively, if the pilot study onsublingual immunotherapy is successful, we would like to develop an oral allergendelivery system suitable for use in dogs.Required resourcesIn a recent meeting, we realized that the limiting factor to the implementation of ourcurrent goal is time. We have planned to examine, at the end of September, if we couldjoin funds to hire a post-doctoral fellow to take on the leadership of our probiotic projectin 2009. Upon obtention of preliminary results, then we will reapply for extramuralfunding. If funding were to be identified for such fellow, then the project will movefurther immediately.100

NCSU Center for Comparative Medicine & Translational ResearchBiostatistics Core Self-EvaluationMarie Davidian, PhDBiostatistics Core LeaderOverviewThe focus of the Biostatistics core is on the development of new statisticalmethodologies addressing data analytic challenges arising in research in medicine,pharmacology, and public health. Core members have expertise in key areas relevantto CCMTR research, including statistical methods for the design and analysis of clinicaltrials; bioinformatics and computational biology; statistical genetics, including methodsfor identifying susceptibility genes for complex traits; cutting edge approaches for theanalysis of longitudinal and time-to-event (survival) data; methods for interpreting highdimensionalinformation, and methods for taking into account missing and mismeasuredinformation. A list of members of the Core and their major research interests is givenbelow. These members are available to collaborate with CCMTR investigators onstudies that involve complex data structures, complicated questions and challenges,and logistical and other features that render standard, routine statistical methodsinappropriate and demand the need to apply cutting edge techniques and to developnew methodological approaches. Statistical collaboration, where health scientists andstatistical scientists work on an ongoing basis as a team on projects of this nature, is tobe distinguished from routine statistical consulting, where a statistician assists aninvestigator by implementing standard analyses. The Biostatistics core is not meant tobe a service resource for statistical consulting. Rather, collaborations betweenmembers of the Biostatistics core and other CCMTR cores ideally should advance boththe health science and statistical science, with the former benefiting from the use of themost modern and tailored statistical techniques for design and interpretation.AccomplishmentsMembers of the Core have been very successful securing external funding from theNational Institutes of Health and the National Science Foundation for research grantssupporting their methodological work, with almost all Core members serving as PI orCo-PI of at least one major methodological grant. Several Core members have initiatedcollaborations with members of other cores on problems including clinical trial design,bioinformatics analyses, and biological systems modeling.ChallengesA key challenge is integrating the Biostatistics Core within the CCMTR. Although therehave been specific instances of collaborations between biostatisticians in the Core andCCMTR members, overall, the interaction has not been extensive. This may be in partdue to the lack of a systematic mechanism for familiarizing CCMTR members with theexpertise of the Biostatistics Core members and the Core’s mission. An additional issueis making explicit the distinction between routine statistical support and more in-depthcollaboration. Biostatistics Core members may be reluctant to take the first steps ingetting involved in CCMTR projects for fear that the main activity may turn out to be anisolated uncompensated routine consulting episode that does not lead to a collaborative101

elationship, for which they may have little time given their other commitments and grantactivities. Likewise, CCMTR scientists may be seeking only routine statistical supportfor a specific project and may not be inclined toward establishing longer termcollaborative relationships. A major challenge facing the Core is how to surmountthese obstacles of perception and logistics and catalyze interactions that will lead tomutually beneficial relationships.Future goalsIntegration of the Core with the activities of the CCMTR and its members is a mainobjective, with the overarching goal of enhancing the efficiency and sophistication of thestudies carried out and the statistical methodology available for the unique challengespresented. A broader goal is for CCMTR members to have access to statistical supportof all types, from routine consulting to collaborative activities involving new methodsdevelopment. One possible approach is for a formal compensated arrangement forroutine consulting help for CCMTR members to be established between the Departmentof Statistics and CVM. With such an arrangement in place, the delineation betweenroutine statistical support and collaborative activities would be clear. This would alsoserve as a conduit for initiating collaborations with Biostatistics Core members, as theconsultant could identify when the issues involved in a project require moresophisticated statistical techniques and connect the scientist with the appropriate Coremember with whom s/he could collaborate.Required resourcesA formal arrangement for provision of routine statistical consulting services between theDepartment of Statistics and CVM would be beneficial.Core members: All Core members are faculty in the Department of Statistics.• Marie Davidian, core leader: Longitudinal data analysis, design and analysis ofclinical trials and observational studies, pharmacokinetic/dynamic analysis,mathematical-statistical modeling of biological systems• Howard Bondell: Variable and statistical model selection, robust inference• Sujit Ghosh: Bayesian statistics, analysis of time-to-event (survival) data• Lexin Li: Bioinformatics, dimension reduction for high-dimensional data, machinelearning and data mining• Wenbin Lu: Analysis of time-to-event (survival) data, longitudinal data analysis,statistical genetics• Jason Osborne: Microarray analysis, design of experiments• Eric Stone: Bioinformatics• Anastasios (Butch) Tsiatis: Design and analysis of clinical trials andobservational studies, analysis of time-to-even (survival) data, methods forhandling missing and mismeasured data, methods for early stopping of clinicaltrials• Jung-Ying Tzeng: Statistical genetics, genetic association studies• Daowen Zhang: Analysis of longitudinal data, design and analysis of clinicaltrials, epidemiology, analysis of categorical data102

NCSU Center for Comparative Medicine & Translational ResearchClinical Genomics Core Self-EvaluationJorge Piedrahita, PhDClinical Genomics Core LeaderOverviewThe Clinical Genomic core is one of the largest cores of the CCMTR and is composedof 26 members, representing 11 different departments across 6 colleges. It coversareas ranging from the genomics of canine cancer to transgenic manipulations inspecies as diverse as swine ands chickens. Due to its large size the core functions as acombination of smaller groups that work together in similar disciplines. For instance,one of the strongest areas of the core is canine genomics. In this area there aremultiple investigators including Mathew Breen, Stephen Sutter, Marlene Hauck,Natasha Olby, and Greg Gibson. This group is very active and has a stronginternational reputation. Another working group within the core is the transgenicmanipulation group composed of Bob Peters and Jorge Piedrahita (swine), and JimPetite (Avian). A collaboration that has been quite successful has been that betweendevelopmental biologists such as Nanette Nascone-Yoder and Jeff Yoder with smallmolecule investigators such as Alex Dieters. This has resulted in both internal(CCMTR) and external (NIH R01) funding. More recently efforts have been made todevelop a working group focused on stem cells and regenerative biology. An initialinterest meeting was held and more than 30 CCMTR members participated. Out of thatinitial meeting a journal club was put together by Troy Ghashghaei. A closecollaboration was developed between the neurology group (Natasha Olby), the stemcell biology group (Troy Ghashghaei) and the swine transgenic group (JorgePiedrahita). In addition there have been collaborations in the area of reproductivebiology (Char and Peter Farin) and textiles (Allan Tonelli) in the area of delivery ofbioactive molecules using new chemical complexes. Overall, the core worksreasonably well in spite of its heterogeneity.Accomplishments1. An R01 between Alex Dieters and Jeff Yoder in the area of development ofchemically inducible switches has been funded.2. Two R21 grants have been funded in the area of swine transgenic. One led byBob Peters to develop a swine model of macular degeneration. This project alsoincludes Brian Gilger a clinician specializing in eye disorders. A second R21 ledby Jorge Piedrahita in the area of Marfan syndrome was also funded. Thisproject has extensive clinical collaborators, both members of the clinicalgenomics core and other cores.3. Collaboration between the Oncology core and the Clinical genomics coreresulted in a K25 grant being funded to study ovarian cancers in chickens.4. In collaborations with other cores we have participated in grants to obtain a Zeissmicroscope, an NIH training grant, and the CTSA grant centered at UNC.103

Challenges1. One of the greatest challenges of this core is its heterogeneity. We are both toolarge and too broad. To be successful we need to identify key areas where wecan be competitive and form smaller working groups in those areas, which canthen start to develop interaction with others groups. That was our approach forthe development of the stem cell group and so far it seems to be working.2. On a more specific challenge, the stem cell biology area would be greatlyenhanced by recruitment of new faculty members with specific interest in theclinical application of stem cell technology. At present this group is formed bymembers who have other main responsibilities, so while it works it would bemore effective if there was a strong stem cell person with the specificresponsibility of leading this subgroup.3. A larger barrier to the continued growth of this group, as well as others within theCCMTR, is the lack of animal housing facilities-- in particular those associatedwith non-rodent species such as swine. Even now, when the CCMTR is young,we already have to turn down potential collaboration with others groups acrossNorth Carolina due to lack of space to complete such projects. Thus, thisimpacts both our own internal growth and our ability to extend our influencebeyond NCSU. It is particularly disappointing that at a time when we are makingsuch positive strides, and can make seminal contributions in clinical andtranslational research, there has been limited support on main campus forinvesting in such a biomedical facility.Future Goals1. Continue to develop the stem cell/regenerative biology group.2. Continue to develop interactions with members of other CCMTR cores.3. Move from the R21 mechanisms to R01s.4. Develop a comprehensive plan to obtain and fund a biomedical research unit thatcan be used for translational research capable of housing animals such as dogsand swine.Required Support1. A faculty position in the clinical applications of stem cells.2. Support for the development of a biomedical research unit capable of housinganimals such as dogs and swine.104

NCSU Center for Comparative Medicine & Translational ResearchEmerging and Zoonotic Diseases Core Self-EvaluationGregg Dean, DVM, PhDActing Head, Emerging and Zoonotic DiseasesOverviewThe Emerging and Zoonotic Disease (EZD) core is comprised of 31 faculty from theColleges of Agriculture and Life Sciences and Veterinary Medicine. A total of sixdepartments (Molecular Biomedical Sciences, Clinical Sciences, Population Health andPathobiology, Poultry Science, Food Science and Microbiology) are represented.Twenty faculty list the EZD core as their only Center affiliation, 11 faculty are affiliatedwith one or more research cores in addition to EZD. Of the 31 faculty affiliated with thecore, 16 have clinical responsibilities in addition to contributing to the research missionof the Center. Faculty in EZD have productive research programs and study a variety ofpathogens including viruses, bacteria, parasites, and protozoa from severalperspectives including food safety, population health, environmental health, vaccinedevelopment and immunopathogenesis. When solicited, the EZD faculty has beenwilling to meet, present data, and consider novel collaborative and fundingopportunities.AccomplishmentsThe spectrum of interests have made it difficult to identify NIH grant opportunities thatwould have a core-wide impact especially since many RFPs are limited to selectinfectious agent research. However, there have been many grant submissions withintra-core collaborations (21) and additional proposals that feature inter-corecollaborations (6) for a total of 27 grant submissions. Of those, 14 were funded at atotal of $2,916,356; 8 are pending and 5 were not funded. At minimum, $537,875 infunding resulted from new collaborations.The EZD has also been brought together in training efforts. Six of the trainers onthe NIH T32 come from the EZD. Importantly, members of the core are reaching out toengage each other through graduate committees. Graduate committees are anexcellent way to gain familiarity with a colleague’s research program and can serve as aplatform to launch additional collaborations. Lastly, members of this core are comingtogether to establish an intellectual exchange group involving NC State, UNC-Ch,NIEHS, and NC Public Health. The topic is ‘One Medicine’ and a primary goal is tobring veterinary (NC State) and medical (UNC-Ch) students together so that they betterunderstand their medical counterpart and appreciate the value of collaboration. Ofcourse, this will also bring established faculty from the participating institutions togetherwith the hope of establishing new multidisciplinary teams.The addition and expansion of the Flow Cytometry service core and the additionof the BSL3 Facility service core to the CCMTR were supported in large degree by EZDfaculty. These facilities have clear benefit for investigators working on infectiousdisease and immunity.105

ChallengesA major challenge for the EZD core is leadership and direction. Due to changes in thedepartmental structure at the CVM, the faculty involved in infectious disease researchhas lost its identity. Hopes that this would be corrected through a ‘cluster hire’ ofseveral new infectious disease faculty and a senior immunologist have withered as mostof these positions were never filled. However, independent of each other, several EZDmembers have moved into the area of vaccine research. This area in particular couldbe exploited given the right funding opportunity. Greater subsidy of service cores wouldenhance the utilization of technology that is already available.Required ResourcesResource needs fall into three categories: new faculty, laboratory animal resources, andsubsidized service core technology. Currently, the core is without a permanent leader.A well-established investigator whose expertise bridges that of EZD members is neededto provide leadership in both research and graduate teaching. Laboratory animalfacilities continue to be inadequate in capacity and quality for virtually any species usedby core members. Lastly, expanded and additional service cores would facilitateresearch achievements. In some cases, the equipment is available, but the cost to useit is prohibitive. Thus, subsidized service cores would make better use of existingequipment while increasing investigator productivity. It would be optimal if the centercould secure a NIH grant that would provide support to service cores.106

NCSU Center for Comparative Medicine & Translational ResearchMucosal Pathophysiology Core Self-EvaluationPhilip L. Sannes, PhDMucosal Pathophysiology Core LeaderOverviewThe Mucosal Pathophysiology Core consists of 19 faculty with appointments in fourNCSU colleges (Agriculture and Life Sciences, Physical and Mathematical Sciences,Engineering, and Veterinary Medicine) and six departments (Molecular BiomedicalSciences, Clinical Sciences, Population Health and Pathobiology, Animal Science,Poultry Science, Biomedical Engineering). Nine faculty have clinical responsibilities.Early assessment of the strengths and interests of members of the Core lead todefining five distinct groupings: Gastrointestinal Group (8 members), Respiratory Group(5 members), Innate Immunology Group (2 members), Ophthalmology Group (2members), and Biomedical Engineering (1 member). The interactions betweenmembers of these groups vary widely, with some being more autonomous than others,while all rely on strong individual programs with track records of accomplishment andsuccess. For the most part, the Core is still in the relative early stages of learning aboutone another and what the prospects may be for meaningful collaboration.Initial surveys of the Core members indicated that most (12) envisionedthemselves as focusing in the area of epithelial research in the long run, followed bytherapy/diet (8), infections and inflammation (8), injury disease and repair (5), stem cells(2), and immunity (2). The first three categories would seem to hold a good degree ofpromise for forming solid working groups for collaboration and pursuit of fundingopportunities.AccomplishmentsProject Funding – Core members are presently involved in approximately 15investigator initiated research grants (funded or under consideration), 4 collaborativegrants, and 3 program initiatives with in the works or planning stages).Symposium – A gathering of area researchers is planned around the Core’s primarythemes for the middle of this academic year. It should be useful in furthering thedevelopment of Core identity and collaborative interactions within and outside thegroup(s).ChallengesThe biggest challenge facing the Core is the development of a cohesive, functionallyinteractive group. Given the diversity of the backgrounds but common themes of theresearch, this should not be an insurmountable task. Strengths of the overall group aresystems biology diversity, multiple methodologic approaches, strong translationalapplicability, experienced, funded investigators, and collaborative histories. Leadershipfor this group will be key in how they coalesce and merge into solid scientific groups.107

Required ResourcesSurveys of Core members indicated that resource needs/interests fell into fivecategories (in the order of the number interested): proteomics, animals housing (large),surgical manipulation, imaging, and robotics. Acquisition of resources in these areaswould serve to facilitate group interaction and collaborative activities.108

NCSU Center for Comparative Medicine & Translational ResearchOncology Core Self-EvaluationJon Horowitz, PhDOncology Core LeaderOverviewThe Oncology core is comprised by 30 faculty with primary appointments in four NCSUcolleges (Agriculture and Life Sciences, Physical and Mathematical Sciences,Engineering, and Veterinary Medicine) and nine departments (Molecular BiomedicalSciences, Clinical Sciences, Population Health and Pathobiology, Poultry Science,Chemistry, Chemical Engineering, Molecular and Structural Biochemistry, Microbiology,and Environmental and Molecular Toxicology). Eighteen faculty list the CCMTROncology core as their only Center affiliation, 12 Oncology faculty are affiliated with oneor more research cores in addition to Oncology. Of the 30 faculty affiliated with thecore, 13 have clinical responsibilities in addition to contributing to the research missionof the Center.With the founding of the Oncology Core, an informal survey was performed toassess strengths and weaknesses with respect to research expertise, sharedresources, equipment, and funding for trainees. On a positive note the Core housesclinical and basic research programs that span a wide variety of cancer-related fields,including the intricacies of protein/protein and protein/DNA interactions, cell-cyclecontrol, cancer immunology, experimental carcinogenesis and toxicology, cancergenetics, epigenetics, development of novel animal models, pathology, cancertherapeutics, and patient pain management. Many of these laboratories have long trackrecords of research success, are well-funded by extramural agencies, and feature labsoutfitted for conducting cutting-edge science as well as a wealth of technical expertise.With that said, the Core is not particularly “deep” (i.e., the Core does not, in general,include groups of investigators focusing on a particular topic). This survey alsorevealed that there was minimal communication between basic and clinicalinvestigators, as well as between most basic research laboratories. In general, basicresearch labs functioned as independent entities with little awareness of ongoing effortsacross campus, or for that matter, "down-the-hall". As a consequence, there were onlya few examples of like-minded, collaborating investigators that had formed interestgroups in pursuit of common goals.A number of infrastructural deficiencies were also noted. For example: (1) theCore did not have access to an in-house bank of oncology specimens and associatedclinical information, nor were plans in place to bank samples collected from theOncology clinic. (2) The Core did not have access to in-house shared resources thatare commonplace at human biomedical centers, such as facilities for the production ofpolyclonal and monoclonal antibodies, screening of DNA or tissue microarrays,production of transgenic and knockout animals, automated DNA and proteinsequencing, high-throughput genotyping, and production of viral vectors. (3) Extramuraltraining grants to support the recruitment and training of graduate students, post-docs,and DVM/PhD students were not available and fellowship programs offering interns andresidents opportunities to perform basic research were non-existent. Finally, (4) with109

espect to the training of graduate students it is worth mentioning that very little didacticteaching of cancer biology was available at NCSU and a formal seminar programhighlighting basic cancer research did not exist.AccomplishmentsSince the founding of the Core, a number of positive developments have occurred thatbode well for the future.1. Project Funding. As a consequence of the first Center faculty meeting, six Coreinvestigators (Anderson, Mozdziak, Pettite, Muddiman, Hawkridge, Horowitz)with diverse expertise but common research interests joined forces to determineif a proteomic analysis of avian ovarian cancer could be used to identifybiomarkers for the early-detection of human ovarian cancer. This study led to thesubmission of a K25 application that was funded for five years. To my knowledgethis application was the first new project to be funded as a consequence of theformation of the CCMTR.2. Infrastructure Funding. As part of an ongoing effort to improve the resourcesand technologies available to CCMTR investigators, an S10 application wassubmitted on behalf of seven CCMTR investigators (Yoder, Nascone-Yoder,Piedrahita, McGahan, Sherry, Rodriguez-Puebla, Horowitz) to obtain a novelmicro/macro zoom microscope that will facilitate ongoing and new studiesinvolving relatively large subjects (e.g., zebrafish embryos, developing transgenicmammals, as well as whole organs or sections from adult animals). Thisapplication was funded and this microscope has been installed.With the development of the CCMTR Clinical Studies Core and the funding ofdesignated Core personnel, Oncology Core investigators have access tospecimens from the Oncology clinic as well as associated clinical information.With the funding of a position for a dedicated Clinical Studies veterinarian andextramural support from Novartis, Core investigators will have an expandedopportunity to study the efficacy of novel therapeutics.3. Didactic Teaching. To facilitate the training of graduate students in cancerbiology, a new four credit course was developed (CBS 771/TOX 771) that will beoffered in the Fall of 2008. This comprehensive course focuses on the molecularand cellular bases of cancer, and is designed to expose graduate students to awide variety of techniques and strategies used in identifying and combatingpathways deregulated in cancer cells. This course will be team-taught by fivefaculty (Tsuji, Ninomiya-Tsuji, Rodriguez-Puebla, Smart, Horowitz), three ofwhom are members of the Core.4. Training Funding. To facilitate the training of the next generation of cancerbiologists, a proposal was submitted by four NCSU faculty (Cavanagh, Lindsay,Melander, Horowitz) to the V Foundation for Cancer Research. This proposalwas written to facilitate the training of high school students, undergraduates, andgraduate students in inter-disciplinary cancer research conducted in the fourfounding laboratories. The V Foundation has agreed to provide $1 million over afour year period to support this endeavor, entitled the Jimmy V/NCSU CancerTherapeutics Training Program. Additional funds are being raised from a numberof extramural sources that will enable this Program to be expanded to include110

additional members of the Oncology Core and thus provide a broader trainingenvironment for students interested in a career in cancer research.With the funding of the CCMTRTP by the NIH and the initiation of the combinedDVM/PhD program, additional resources are now available for the training ofclinically-oriented students in basic research labs.Challenges1. The Core remains an amalgamation of 30 very busy faculty and associatedlaboratories with only tenuous links to one another. Repeated attempts to bringcore members together for core-specific scientific discussions or strategysessions have met with little enthusiasm. Repeated calls for applications forCCMTR-sponsored pilot grants have, in general, not proven successful. TheCore has yet to generate a substantial number of new projects generated byinteractions between groups that would not otherwise be natural collaborators.Communication between basic research labs, as well as basic and clinicalresearch labs, has not been substantially improved. The Core still does not havea natural setting, such as a common Cancer Biology seminar program, in whichclinical and basic researchers could meet on a regular basis to exchange ideas,become more familiar with ongoing projects, and be exposed to endeavorsoutside of NCSU.2. The Core still does not have in-house access to many of the shared resourcesthat would be expected in a major biomedical research center. Where possible,Core members utilize shared resources at other universities or engage resourcesat commercial establishments.Required ResourcesA major hindrance for research conducted by many Core investigators is functionalspace for large and small animals. A state-of-the-art vivarium for small animals wasconstructed on the first floor of the CVM Research Building (this building was occupiedby CVM investigators in 2004), yet the vast majority of the animal rooms were notoutfitted with racks accommodating individual ventilated cages (IVC; each room wasdesigned such that mice could be housed in this fashion). As a consequence, IVCmouse space is at a premium and this constrains experiments requiring large numbersof animals (e.g., tumor-induction studies, breeding of "knockout" and transgenic mousecolonies). Large animal space for experimentation is virtually non-existent on the CVMcampus, and is difficult to find at other NCSU facilities.111

NCSU Center for Comparative Medicine & Translational ResearchClinical Studies Core Service Core Self-EvaluationMarlene Hauck, DVM, PhDSteering Committee chairOverviewThe mission of the CCMTR Clinical Studies Core is to support interactions betweenclinical and basic research groups within NC State University and to expandcollaborative relationships beyond the university with practicing veterinarians, animalowners, and industry partners. The CSC offers support through the following services:• Assistance with all aspects of clinical investigations, including publicity and caserecruitment, patient enrollment, patient visits, sample collection and processingand patient follow-up• Resources for investigators in the design and implementation of clinical studies.• Oversight for a repository of veterinary tissue samples to support ongoing anddeveloping studies• A biospecimen procurement service for researchersAccomplishmentsSpace for the CSC was allocated in the Firestone Wing of the CVM. This spacerequired retrofit to convert the existing laboratory space to a combination of laboratory,office, and tissue banking equipment. The CSC selected two software programs tomanage the tissue banking (AIM TissueMetrix) and clinical investigations(StudyManager) aspects of the lab. Numerous interactive training sessions wereattended to become proficient in each program and a large amount of customprogramming was necessary to adapt the TissueMetrix software to veterinary medicine.The CSC was required to follow a series of administrative procedures to comply with thelab acting as a fee-for-service core and interacting with client owned animals presentingto the VTH. These requirements included:• Establishing a Trust Fund account and Use Rates based on Contracts andGrants requirements• Creating storage and service contracts and owner informed consent templatesand presenting these to NCSU Legal Services and the VTH Hospital Board forapproval• Obtaining IACUC approval for sample collection• Creating budget worksheets and accounting protocolsNext, efforts were directed at publicizing CSC services. This included:• Creating a graphic identity for posters, brochures, mailings and websites• Design and implementation of a website112

• Meetings with College faculty and clinical technicians to introduce them to theservices of the Clinical Studies CoreAnother major focus was the development of educational and recruitment material forreferring veterinarians and pet owners to publicize and facilitate ongoing VTH clinicalstudies. There are numerous clinical studies that are underway in the VTH at any giventime, but the college lacks a consolidated, comprehensive means to communicate thisinformation to the referral and pet-owning communities. Specific activities to achievethis goal have included:• Surveying of all VTH clinicians performing clinical studies, and compilation of alisting of all ongoing VTH clinical studies• Design of the website to include sections for referring veterinarians and petowners, that include a listing of all current studies and frequently asked questionson participation in veterinary clinical studies• Creation of an electronic mailing list to send area veterinarians monthly updateson ongoing clinical studies, which was approved by the VTH Hospital BoardThe CSC is now involved in 13 projects:• Early testing of a medical device (1)• Prospective banking of tissue samples from VTH patients (2)• Collection of blood samples from VTH patients for ongoing research studies (7)• Secure storage of experimental samples (2)• Recruitment of patients for an ongoing clinical trial (1)ChallengesOne of the greatest challenges faced by the CSC has been the need to “blaze a trail” forthis new, unique service. Much of the infrastructure and operating procedures had to beestablished or negotiated. This was made especially difficult by the fact that the CSCrequires multi-departmental interaction that spans the entire college and beyond, ratherthan being neatly housed within a single department.Another challenge has been obtaining faculty and staff “buy-in.” Many CVM and VTHemployees are immediately excited about the chance to work collaboratively and arewilling to give the extra time and attention needed to move clinical research forwardthrough the CSC. Others seem to be unconvinced by the potential of the CSC to givethis extra effort. Further marketing of the service and a demonstrable track record ofsuccesses will be needed to win over these individuals.Future GoalsFuture goals of the CSC include:• To see steady and constant growth of active projects with NCSU and CVMfaculty• To become financially self-supporting in five years113

• To see a return on the investment of CSC-initiated tissue banking throughpurchases of these samples by researchers• To begin projects with and prospective banking of tissues from large animal, foodanimal, and exotic species• To develop relationships with external veterinary practices and industry clientsRequired ResourcesTo achieve these goals, the CSC will require:• Continued salary support for technicians and a veterinarian• An annual operating budget that grows commensurate with the growth of theprogram• Space for patient exams, treatments, housing, and monitoring• Space for secure storage of study supplies and records• Space for additional tissue banking and laboratory equipment• A non-reverting revenue account to allow the accumulation of funds needed topurchase equipment, pay salaries, and become self-supporting114

NCSU Center for Comparative Medicine & Translational ResearchBSL3 Service Core Self-EvaluationEdward B. Breitschwerdt, DVMBSL3 Service Core DirectorOverviewCVM administration, recognizing the new national focus on emerging diseases and highrisk agents, incorporated BSL3 laboratory space into the design of the ResearchBuilding which was occupied April, 2005. The intention was that the BSL3 Laboratorywould be used in support of CVM and NCSU researchers and any of their collaboratinginstitutions pursuing investigations that required containment of airborne bacteria,viruses, or toxins. The BSL3 Biocontainment Facility is available for use under thedirectorship of Edward B. Breitschwerdt, DVM, and the management of BarbaraHegarty, BA. The design and administration of the BSL3 Biocontainment Facility followsstrict federal regulations with local oversight provided by the NCSU InstitutionalBiosafety Committee. These and other factors assure the community that infectiousdisease research will not result in occupational hazards for the occupants of theresearch building. Beyond these intentions, no directives or limitations have been statedby CVM.AccomplishmentsBy September, 2005, the BSL3 Biocontainment Facility had successfully undergone atwo part inspection by World BioHazTec, a third party commissioning agency thatdetermined that the facility’s design and operations met all federal regulations. SinceCVM administration had intended the facility to be operated as a service center, theOffice of Contracts and Grants authorized a daily user rate of $71.84 based upon theestimated yearly operating costs.In 2007, the Center for Comparative Medicine and Translational Research wasestablished and the CVM BSL3 Facility was placed under this umbrella. As a result, theBSL3 Facility has a presence on the Center’s website with information available to anyinvestigators seeking specialized research facilities. The BSL3 Facility participated inthe Pilot Project Symposium that took place May 15, 2008 with a 5 minute presentationgiven by Barbara Hegarty in order to inform CVM members of the opportunitiesavailable through the various core service labs.A number of NSCU faculty and researchers representing institutions outside ouruniversity have expressed interest in using the facility but in most cases have notfollowed up after initial inquiries. In May 2008, a pilot grant through the CCMTR wasawarded to a DOCS faculty member for 3-4 months of BSL3 Facility usage representingthe first revenue generated by the Facility ($3000.00).In a more productive direction, the Facility has provided some educationalresources to the University in the form of tours for students interested in the applicationof biosafety and biosecurity principles for agricultural and production animal research.In addition, our presence as a functioning and successfully commissioned BSL3 lab hasbeen recognized as we have been called upon in a number of instances to provide115

advice and procedural materials to assist others in preparing new laboratories, includinganother BSL3 lab opening in Polk Hall at NCSU in Fall of 2008.In May, 2008, Dr. Prema Arasu, Director of Global Health Initiatives at NCSU,asked CVM BSL3 Facility if we were interested in participating in a proposal forbiosafety training related to avian influenza in Thailand. This proposal was submitted tothe USDA in collaboration with UNC and with Dr. Jonathan Richmond, a privateconsultant working in the field of biosafety and biosecurity. Our participation was toprovide space and two to three days of training for visiting Thai scientists. The fundingfor this educational initiative was not awarded to NCSU-CVM.In an effort to build on the strengths of our presence and as circumstances seemto be directing us, progress has been made with the CVM Office of ContinuingEducation to bring a course in biosafety concepts and practices into being here at CVM.Dr. Royden Saah and Ms Holly Lee, experienced technicians in a biosecurity laboratory,had expressed interest in forming a nonprofit company whose purpose would be thetraining of researchers and technicians in the procedures necessary for working inbiocontainment at BSL3 levels. Their concept is being incorporated into an initiative tooffer training here at CVM. This course is envisioned as being a two part course, onepart in lecture format to present concepts of biosafety and biosecurity and how theseare handled in an academic environment and the other a day-long, hands-onintroduction to functioning in the BSL3 lab environment. The first course is anticipated tobe offered in Dec, 2008.ChallengesTo prepare more adequately for the potential use of our facility by outside agencies,Bruce Macdonald of NCSU EH&S contacted the CDC on our behalf to discover how weshould proceed when a company that is not under the jurisdiction of the university usesuniversity facilities especially when using a pathogen that is considered a select agentby the USDA. Concerns expressed were over how we would set up a contract thatwould maintain our control over work done in the event that there are any infractions ofthe operating rules and procedures. The CDC’s ruling was that we should not allowoutside agencies to conduct select agent work in the NCSU-CVM BSL3 Laboratory.Additionally, a meeting in Jan. 2007 was arranged with NCSU legal council andCentennial Campus Development Office to formulate a plan to include facilityattributes/constraints and leasing issues relative to an unrelated third party, IP rights,and partnership programmatic connection. This meeting concluded with the offer of helpfrom these parties but that actual agreements would be formulated whenever an outsideagency approached us for BSL3 Facility use.The major challenge to full utilization of this facility, may be a shortage ofresearchers who are willing to commit to the extra restrictions and regulations imposedupon work requiring oversight by federal, state and institutional agencies along withlimited funding sources especially as found in veterinary sciences for the study of highlypathogenic organisms. A concerted effort may be needed on the part of CVMadministration to recruit researchers with interests in infectious diseases or vaccineproduction.116

Future goalsTo support those researchers who are willing to invest time and effort into infectiousdisease research in spite of the many obstacles imposed by current Federal regulations,the CVM BSL3 Facility stands ready to guide and assist in the management ofpaperwork and to provide a safe environment in which to work. It is hoped that a CEcourse of the sort scheduled for December, 2008 will provide an outreach effort that willpublicize the existence of the facility at the same time that it encourages a balancedunderstanding of biosafety and biosecurity issues without fostering fear in the academicand public community surrounding any such facility. The audience targeted for theconcepts part of the course would include academic or corporate advisors involved inbiosafety committee oversight, building planning, and management of federal and stateregulations pertaining to biosafety. The target for the hands-on portion would beresearchers or students that wish for practical experience to support their decision towork in areas that require BSL3 level protection.Required resourcesNIH guidelines of 2008, suggest recertification on an annual basis for Biocontainmentlabs. We had previously determined that recertification would be every five years or onan as needed basis. The initial certification in 2005 cost the CVM $13,800.00. A recentbid from World BioHazTec Corp. would not exceed $4300.The Training course would require a one time investment in PAPRs (Powered AirPurifying Respirator @$741 each) for 6-10 units to be used in demonstrations andpractice of proper personal protection for some aerosolized pathogens. An outsidesource for these costs would be beneficial to keep registration fees within range of asmany technicians and scientists as possible (current estimate is ~$300/ registrant).Supplementation of registration fees would also be helpful.117

NCSU Center for Comparative Medicine & Translational ResearchFlow Cytometry & Cell Sorting Lab Service Core Self-EvaluationMary Tompkins, DVM, PhDFlow Cytometry & Cell Sorting Lab Service Core LeaderOverviewThe NCSU Flow Cytometry and Cell Sorting Laboratory provide instrumentation andassistance for multi-parameter flow cytometric analysis and sorting. The Laboratoryoperates as a by appointment, fee for service laboratory. The manager of thelaboratory and equipment operator is Ms. Janet Dow, and the faculty director is Dr.Mary Tompkins.Analyzers: The laboratory contains two analyzers (a Becton-Dickinson FASCan and aB-D FASCaliber) in the main laboratory located in the main CVM building and a thirdanalyzer (a B-D LSR II) in the CVM Research building. The FASCan has a single argonlaser (488nm) and can provide data for forward and side scatter along with 3 colors offluorescence. The FASCaliber has the same capabilities as the FASCan as well as asecond laser (633nm) and is capable of 4-color analysis. The LSR II has3 lasers(405nm, 488nm, and 635nm) and is capable of at least 6-color analysis.Cell Sorter: The laboratory’s sorter is a Cytomation Inc. MoFlo, capable of sortinggreater than 50,000 cells/sec with recovery rates of 90% or greater. The instrument isconfigured with a Blue Sappire 488nm laser, a Melles Groit Helium-Neon laser (633nm),and a UV laser that is tunable but normally operates at 350nm. The MoFlo is capable ofanalyzing up to 10 colors plus forward and side scatter. In terms of sorting capability,the MoFlo can sort for up to 4 different cell populations at once and is capable ofpurifying populations that are less than 1% of the total input population.Computers and Software: The two analyzers in the main CVM building are operatedusing Macintosh G5 computers with BD Cell Quest Pro software. The LSR II isoperated using DIVA software. The MoFlo is operated using a PC computer withSummit software. In addition, the laboratory has FloJo and Modfit software available foruse. Data analysis can be done using the analyzer computers when data acquisition isnot taking place. There are also 2 Macintosh and 1 PC auxiliary analysis stations.Laboratory/Equipment Use: There are three levels of use of the analyzers with differentfees: Operator (Ms. Dow)-conducted acquisition and analysis ($80/hr); Operatorconductedacquisition, user-conducted analysis ($70/hr); and User-conductedacquisition and analysis (supervised) – ($60/hr). Only the laboratory operator (Ms.Dow) is allowed to run the MoFlo. It may be used for analysis (generally only for >4colors or UV laser use) as well as for sorting ($100/hr).Other services available include help with experimental design, training on theanalyzers, and preparation of figures for publication.118

AccomplishmentsIn the past fiscal year, the Flow laboratory provided service for 27 different laboratorieson campus. A majority of these labs are associated with the Veterinary College and theCCMTR. The lab also added the LSR II analyzer (courtesy of Dr. Gregg Dean).Funding by the CCMTR of a Service Core grant has allowed the development of asorting protocol for epithelial cells. A second CCMTR grant provided funds to purchasethe 405 laser for the LSR II.ChallengesThe main challenge for the laboratory is monetary support. The University provides partof Ms. Dow’s salary, and until this fiscal year, provided 50% of the maintenance contracton the MoFlo. The remaining costs of running the laboratory, including the remainder ofMs. Dow’s salary and the maintenance costs of the analyzers must come from thelaboratory revenue. Thus the user fees are generally higher than Flow laboratories inother Universities. The laboratory would like to lower user fees, believing that theoverall use would increase. However, the laboratory needs some sort of guarantee thatif revenue falls short of expenses, there would be some financial support.Future GoalsWe would like to upgrade the FASCan by adding a second laser and two more PMTs.We would also like to increase use by faculty on the main campus. Eventually we hopeto be able to offer service to Center members at a reduced fee, but this will requiresome sort of financial support.Required ResourcesSalary support for Ms. Dow. Replacement of ancillary equipment (e.g. computer,microscope) when necessary. If a maintenance contract is to be continued for theMoFlo, then more than 50% of cost must be provided from a source other than thelaboratory revenue.119