FA 5 Progress Report WV-INBRE - Joan C. Edwards School of ...

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Program Director/Principal Investigator (Last, First, Middle): Rankin, Gary O 52WV-INBRE:APPALACHIAN CARDIOVASCULAR RESEARCH NETWORK (ACORN) (0006)TYPE: Research Subproject%IDeA $: 11.000% IDeA $: 406,206INVESTIGATOR, DEGREEPrimerano, Donald A PHDBarr, Taura PHD, RNBoskovic, Goran PHDDementieva, Yulia PHDDenvir, James PHDEgleton, Richard BS, PHDFan, Jun BS, PHDKreisberg, Robert PHDMangiarua, Elsa PHDNeal, William MDSantanam, Nalini PHDDEPARTMENTBiochemistry &MicrobiologyNursingBiochemistry &MicrobiologyMathematicsBiochemistry AndMicrobiologyPharmacology,Physiology & ToxBiochemistry &MicrobiologyBiologyPharmacology,Physiology & ToxPediatric CardiologyPharmacology,Physiology & ToxNON-HOST INSTITUTION: STATE,COUNTRYWest Virginia University, Wv UsaEmmanuel College, Ma UsaWest Liberty University, Wv UsaWest Virginia University , Wv UsaTotal # human subjects expected for entire study: 35Total # human subjects enrolled to date: 25SUBPROJECT DESCRIPTIONOverview and Current ACoRN Projects:Cardiovascular disease (CAD) and one of its contributing causes, obesity, are significant healthproblems in West Virginia (WV). West Virginia ranks 6th highest in the rate of heart disease deaths amongthe 50 states and the District of Columbia (Kaiser Family State Health Facts(http://www.statehealthfacts.org/)) and has the highest rate of obesity in the United States. Understandingthe genetic and dietary factors that lead to these two diseases is central to Appalachian CardiovascularResearch Network (ACoRN) research projects.ACoRN is designed to explore the genetic and environmental causes of cardiovascular disease as wellas the mechanism(s) of action of therapeutic agents. Our investigators are currently guiding fourcardiovascular disease research studies and providing mentorship to two undergraduate projectinvestigators at West Liberty University. Under WV-INBRE II, we have broadened the base of cardiovascularresearch, taken measures to improve human subject recruitment and increased the participation ofundergraduate students in ACoRN supported research. Empowerment of individual project investigatorswith appropriate mentoring has broadened the base of ACoRN research and increased the potential ofmaking significant findings on the pathogenesis and treatment of cardiovascular disease.SUBPROJECT PROGRESSACoRN Y11 Progress Report1. Current ACoRN Projects:PHS 2590 (Rev. 06/09)Continuation Format Page
Program Director/Principal Investigator (Last, First, Middle): Rankin, Gary O 53Progress reports for three of the five ACoRN projects are given under separate subproject IDs(SPIDs) in the APR or as part of this report as follows:Project #1: The Molecular Actions of Atorvastatin on Progression of the Atheromatous Plaques(SPID #25). Project Investigator. Robert Kreisberg PhD, West Liberty University. Mentor: N.Santanam, Marshall University.Project #2: The Genetic Basis of Familial Combined Hyperlipidemia (SPID #26). Project Director D.Primerano, PhD. Marshall UniversityProject #3: Epicardial Fat Biomarkers in Patients with Coronary Artery Disease in the AppalachianRegion (SPID #36). Project Director N. Santanam PhD. Marshall University.Progress Reports for Projects #4 and #5 are given below in sections 5 and 6.Project #4: Monitoring gene expression post-stroke to predict stroke outcome. Project Director:Taura Barr PhD RN School of Nursing and Center for Neuroscience, West Virginia University).Project #5: Regulation of brain endothelial phenotype and function by diabetic plasma ProjectDirector: Richard Egleton, PhD, Department of Pharmacology, Physiology and Toxicology, MarshallUniversity).A table providing information on protection against research risks for Projects #4 and #5 is providedat the end of this document.2. ACoRN Management PlanACoRN will consider applications from investigators at both lead and undergraduate institutionsfor new ACoRN research projects. Applications will be reviewed initially by WVU or MU facultymembers, then by the WV-INBRE External Advisory Committee (EAC), and finally by ourNCRR/NIGMS program officer. Approval by the EAC and program officer will be required in order forfunding to be committed to a project. We anticipate issuing a request for applications incardiovascular research and offering pilot grant awards in Y12 and Y13.3. Revision to Genetic Basis of Familial Combined HyperlipidemiaWe have modified our proposal to adopt an approach based on sequencing the exomes ofrelated affected individuals. Whole exome sequencing has successfully been used to identifycausal variants for about 15 Mendelian disorders (e.g. Miller Syndrome, metachondromatosis andKabuki Syndrome. Our immediate and long-range goals remain unchanged. We will improve ourunderstanding of the molecular pathology of cholesterol and triglyceride regulation by identifyinggenes and variants that predispose to FCH.The new experimental design involves several stages: (1) selection of FCH families with multipleaffected individuals who are known to not have deleterious alleles in the LDLR gene, (2) removal ofcommon variants from whole exome sequences by comparison to existing SNP databases suchas HapMap and dbSNP and reduction of coincident variants by selection of variants shared bymultiple affected individuals, and (3) confirmation of the presence of deleterious alleles in otheraffected family members and their absence in phenotypically normal individuals. Through thisfiltering process, we expect to obtain a small number of candidate genes that confer susceptibilityto FCH.We have completed sequencing of LDLR exons in 19 of 21 FCH families and have excluded fourfamilies based on our analysis. We have completed whole exome sequencing on six families andPHS 2590 (Rev. 06/09)Continuation Format Page
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FA 5 Progress Report WV-INBRE - Joan C. Edwards School of ...

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