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: 7483611
• 负责人: JESSICA J CONNELLY
• 金额: $ 8.25万
• 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/7483611
• 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)： 这是一份申请美国国立卫生研究院独立职业发展奖的申请书。该奖项的候选人是人类遗传学中心的NRSA博士后研究员杰西卡·J·康奈利博士。伊丽莎白·R·豪泽博士和西蒙·G·格雷戈里博士将在该奖项的指导阶段担任共同导师。这位候选人提出的指导性研究试图通过基于家族的早发性CAD连接区域的关联分析，并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，来阐明导致冠状动脉疾病(CAD)的分子因素。指导阶段研究的科学重点是对以家庭为基础的CAD人群中的384个SNP进行统计和计算分析。考虑到应聘者在遗传学和分子生物学方面的出色背景，增加对统计学的深刻理解只会提高她未来在实验室内外的工作效率。独立研究阶段的建议使用CAD特定的细胞培养模型来(1)分析环境诱导的高同型半胱氨酸血症引起的DNA甲基化模式的变化，以及(2)在临床人群中确定与CAD相关的表观遗传学特征。