Scientific Report 2003-2004 - Cleveland Clinic Lerner Research ...

Center forSurgery ResearchCENTER FORSURGERY RESEARCHDIRECTORSuyu Shu, Ph.D.The Center for Surgery Research wasestablished in 1995 under the administrationof the Division of Surgery at theCleveland Clinic Foundation (CCF). Since then, acontinued emphasis of our activity and developmenthas been translational research in the areaof tumor immunotherapy. Consistent with thisphilosophy, the Center’s scientific pursuit hasfocused on the analysis of the fundamentalprinciples of host immune responses to a varietyof malignant tumors. It is hoped that throughthis understanding, strategies to enhance tumorantigen recognition by the cells of the immunesystem can be improved. Therefore, the overallgoal and mission of the Center is to provideexcellence in research and education throughbench investigation, preclinical animal experimentationand clinical trials.Our currently have full Staff members(Suyu Shu, Ph.D., Director, Peter A. Cohen,M.D., Julian A. Kim, M.D., and Julian A. Kim,M.D.) and one Associate Staff (David E. Weng,M.D., Ph.D.). In addition, two former researchfellows (Jorgen Kjaergaard, Ph.D., and LiaominPeng, M.D.) have recently been promoted toProject Scientists. Dr. Cohen is a board-certifiedmedical oncologist. His research has beencentered on the mechanisms and functions ofantigen-presenting cells (APCs) present in tumormass. He is also interested in delineating theantitumor effects and mechanisms mediated bytumor-sensitized CD8 T lymphocytes. His workis supported by an R01 investigation grant fromthe National Cancer Institute.Dr. Julian Kim is a surgical oncologist whogained significant experience in clinical T-cellimmunotherapy of colon cancer while at OhioState University in Columbus. Now, Dr. Kimprovides surgical expertise to our group and isinvolved in a number of clinical trials. He hasalso developed his own research projects closelyrelated to immunotherapy of cancer. During thepast two years, Dr. Kim’s laboratory research hasdefined the effects of anti-CD40 monoclonalantibodies on the sensitization of immune T cellsagainst the murine breast cancer 4T1. Anotherline of his investigation has been the inhibitionof vascular endothelial growth factor (VEGF) topromote immune responses to the 4T1 breastcancer. This tumor model has the potential tospontaneously metastasize to various visceralorgans and to the brain, thus providing anexcellent opportunity to investigate the effects ofimmunotherapy against naturally occurring tumormetastases.Dr. David E. Weng has had a primaryappointment at the Center since January 2001;previously, his primary position was in theDepartment of Hematology/Oncology, where hespent 50% of his time in clinical patient care.Transfer to the Center has allowed him to focuson developing scientific research programs andprocedures for experimental clinical trials. Dr.Weng received his undergraduate education fromHarvard University and completed his M.D. andPh.D. degrees at Johns Hopkins University. Hehas already participated in several of our ongoingclinical immunotherapy protocols. In thelaboratory, Dr. Weng has begun work onanalyzing the expression of chemokines and theirreceptors at the site of tumor regression mediatedby transferred T cells. Much progress has beenmade towards delineating the expression of IP-10(interferon [IFN]-inducible protein-10), Mig(monokine induced by IFN-gamma) andRANTES (regulated on activation normal Tlymphocyte expressed and secreted), as well aschemokine receptors such as CCR2, CCR5 andCXCR3. It is an important area of researchbecause the role that chemokines play in thetrafficking and interactions of T cells with tumorhas not been defined.Dr. Jorgen Kjaergaard is a graduate ofUniversity of Aarhus, Denmark, where heobtained his Ph.D. degree in Microbiology andImmunology in 1994. During graduate study, hebecame interested in tumor immunology, workingintensively on the biology and functions oflymphokine-activated killer (LAK) cells. He wasa postdoctoral fellow in Dr. Shu’s laboratory atCCF from 1997-2000. He has since contributedto work on the pattern of systemically administeredT lymphocytes.Dr. Liaomin Peng graduated from the FirstMilitary Medical University, PRC, with an M.D.degree in 1986. He came to CCF in 1996 as apostdoctoral fellow working with Dr. JohnKrauss for about 3 years before working with Dr.Cohen. Prior to his coming, Dr. Peng hadconsiderable experience in molecular biology andtumor immunology. In the past 6 years, he hasworked on various projects analyzing T-cellreactivities against malignancies in preclinicalanimal models. Dr. Peng has defined thesuppression role of a particular T-cell subpopulationin the tumor-draining lymph nodes. He isalso studying the effects of ligation of thecostimulatory molecule OX-40R to enhance T-cell-mediated antitumor immune responses.Staff members in the Center have jointappointments in other CCF departments, such asthe Departments of Immunology, Cell Biology,Cancer Biology, Otolaryngology, Hematology/Oncology, and General Surgery and in the TaussigCancer Center. The Center for Surgery ResearchContinued on Page 168INVESTIGATORSWei Chen, M.D., Ph.D.Peter Cohen, M.D.Julian Kim, M.D.Gregory E. Plautz, M.D.ASSOCIATE STAFFDavid E. Weng, M.D., Ph.D.PROJECT STAFFJorgen Kjaergaard, Ph.D.Liaomin Peng, M.D.167