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

描述（由申请人提供）： 这是NIH独立职业发展奖的申请表。该奖项的候选人是杰西卡·J·康奈利博士，NRSA人类遗传学中心的博士后研究员。伊丽莎白·R博士豪瑟和西蒙G. Gregory将在该奖项的指导阶段担任共同导师。候选人提出的指导研究旨在阐明导致冠状动脉疾病（CAD）的分子因素，使用基于家族的早发CAD连锁区的关联分析，并通过基因组微阵列实验的应用，以确定细胞特异性转录因子结合和DNA甲基化模式。研究指导阶段的科学重点是对基于家庭的CAD人群中的384个SNP进行统计和计算分析。鉴于候选人在遗传学和分子生物学方面的优秀背景，增加强大的统计理解只会提高她未来在实验室内外的生产力。独立研究阶段的提案使用CAD特异性细胞培养模型来（1）剖析响应于环境诱导的高同型半胱氨酸血症的DNA甲基化模式变化，以及（2）鉴定与临床人群中CAD相关的表观遗传特征。

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.