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

心血管疾病的分子解剖：从基因到模型到功能

• 批准号: 7301203
• 负责人: JESSICA J CONNELLY
• 金额: $ 8.07万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7301203
• 关键词: Acetylation; Affect; Apoptosis; Apoptotic; Architecture; Arterial Fatty Streak; Atherosclerosis; Award; Binding; Blinded; Blood Cells; Candidate Disease Gene; Cardiovascular Diseases; Cardiovascular system; Cell Aging; Cells; Chromosomes, Human, Pair 1; Clinical; Complex; Computer Analysis; Coronary Arteriosclerosis; Cultured Cells; Cytosine; DNA; DNA Binding; DNA Methylation; Data; Data Set; Development; Disease; Disease susceptibility; Dissection; Doctor of Philosophy; Endothelial Cells; Enzymes; Epigenetic Process; Family; Foam Cells; Functional disorder; Future; Genes; Genetic; Genetic Population Study; Genetic Transcription; Genome; Genomics; Genotype; Goals; Haplotypes; Hematopoietic; Histones; Homocysteine; Homocystine; Human; Human Genetics; Hyperhomocysteinemia; In Vitro; Individual; K-Series Research Career Programs; Lead; Lipids; Logistics; MTHFR gene; Maps; Mentors; Methodology; Methods; Methylation; Methylenetetrahydrofolate reductase (NADPH); Modeling; Modification; Molecular; Molecular Biology; Monitor; National Research Service Awards; Nucleotides; Null Lymphocytes; Parkinson Disease; Pathway interactions; Patients; Pattern; Peripheral Blood Mononuclear Cell; Phase; Play; Polymorphism Analysis; Population; Postdoctoral Fellow; Predisposing Factor; Predisposition; Productivity; Proliferating; Range; Regression Analysis; Regulatory Pathway; Research; Research Personnel; Resolution; Risk Factors; Role; Scanning; Series; Single Nucleotide Polymorphism; Smooth Muscle Myocytes; System; Techniques; Testing; Training; Translating; United States National Institutes of Health; Universities; Up-Regulation; Variant; acute coronary syndrome; assault; base; bisulfite; career; case control; cell age; cell type; density; design; early onset; epigenomics; gene interaction; gene repression; genome-wide linkage; in vivo; novel; programs; research study; response; transcription factor

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.

描述（由申请人提供）： 这是NIH途径获得独立职业发展奖的申请。该奖项的候选人是杰西卡·康纳利（Jessica J. Connelly）博士，他是人类遗传学中心的NRSA博士后研究员。博士。伊丽莎白·R·豪瑟（Elizabeth R. Hauser）和西蒙·格雷戈里（Simon G.候选人提出的指导研究旨在阐明分子因素，使用基于家庭的早期发作CAD链接区域的基于家庭的关联分析以及通过应用基因组微阵列实验来确定细胞特异性转录因子结合和DNA甲基化模式。研究阶段的科学重点是对家庭CAD人群中384个SNP的统计和计算分析。鉴于候选人在遗传学和分子生物学方面的良好背景，增加了强大的统计理解只会提高她在实验室内外的未来生产力。独立研究阶段的提议使用CAD特定的细胞培养模型对（1）剖析DNA甲基化模式，以响应环境诱导的超粒性半胱氨酸血症，并且（2）确定与临床种群中与CAD相关的表观遗传学特征。