Molecular Dissection of Cardiovascular Disease: From Genes to Models to Function

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DESCRIPTION (provided by applicant): This is an application for a NIH Pathway to Independence Career Development Award. The candidate for this award is Jessica J. Connelly, Ph.D., an NRSA postdoctoral fellow at the Center for Human Genetics. Drs. Elizabeth R. Hauser and Simon G. Gregory will serve as co-mentors during the mentored phase of this award. The candidate's proposed mentored research seeks to elucidate molecular factors that lead to coronary artery disease (CAD) using family based association analysis of an early onset CAD linkage region and through the application of genomic microarray experiments to determine cell specific transcription factor binding and DNA methylation patterns. The scientific emphasis of the mentored phase of research is the statistical and computational analysis of 384 SNPs in a family based CAD population. Given the candidate's excellent background in genetics and molecular biology, the addition of a strong statistical understanding will only enhance her future productivity both in and out of the lab. The proposal for the independent phase of research uses CAD specific cell culture models to (1) dissect DNA methylation pattern changes in response to environmentally induced hyperhomocysteinemia and (2) identify epigenetic signatures that are associated with CAD in clinical populations.