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

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