Genetics of Vascular Remodeling

血管重塑的遗传学

• 批准号: 8302309
• 负责人: SANTHI K GANESH
• 金额: $ 24.54万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-02 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8302309
• 关键词: Acute; Advisory Committees; African American; Age; Alleles; Ankle; Area; Arterial Fatty Streak; Arterial Injury; Arteries; Atherosclerosis; Award; Biology; Blood; Blood Cells; Blood Vessels; Candidate Disease Gene; Cardiology; Cardiovascular Diseases; Cardiovascular system; Carotid Artery Plaques; Caucasians; Caucasoid Race; Cessation of life; Chromosome Mapping; Chromosomes; Clinic; Clinical; Cohort Studies; Collaborations; Complex; Coronary; Coronary Arteriosclerosis; Coronary artery; Data; Databases; Development; Disease; Enrollment; Environment; Epidemiology; Event; Faculty; Family; Family Study; Fellowship; Functional disorder; Funding; Future; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Transcription; Genome; Genomics; Genotype; Goals; Haplotypes; Harvest; Health; Heart; Heart Transplantation; Hospitals; Human; Indolent; Inflammatory; Injury; Intramural Research; Investigation; Ischemia; Laboratories; Lesion; Literature; Maps; Mentors; Methods; Modeling; Molecular; Molecular Genetics; Myocardial Infarction; National Human Genome Research Institute; Oligonucleotide Microarrays; Outcome; Pathway interactions; Patients; Peripheral Blood Mononuclear Cell; Phase; Phenotype; Positioning Attribute; Predisposition; Principal Investigator; Process; Program Development; Prospective Studies; Publishing; RNA; Radionuclide Imaging; Research; Reverse Transcriptase Polymerase Chain Reaction; Risk; Sampling; Scientist; Sequence Analysis; Siblings; Single Nucleotide Polymorphism; Stents; Stress; Susceptibility Gene; Testing; Thallium; Time; Tissue-Specific Gene Expression; Tissues; Training; Transcript; United States National Institutes of Health; Universities; Validation; Variant; Vascular Diseases; Vascular remodeling; Woman; Work; base; biobank; career; career development; case control; cdc Genes; chromosome 5q loss; cohort; density; disease phenotype; follow-up; genetic analysis; genetic linkage analysis; genetic variant; genome wide association study; human subject; human tissue; implantation; indexing; injured; insight; men; novel strategies; post-doctoral training; premature; proband; programs; repository; response; response to injury; restenosis; skills; trait

DESCRIPTION (provided by applicant): This proposal describes a five-year program for the development of an academic career in cardiovascular genomics. I have completed a clinical cardiology fellowship and three years of postdoctoral training at the NIH. I now will expand my scientific skills in molecular, statistical and epidemiologic principles necessary for the analysis and interpretation of bias-free studies of genomic associations, through the genomic analysis of a complex cardiovascular disease. Over the course of this award, I plan to transition to independence and build upon work completed as a fellow, to investigate the genetic basis of vascular remodeling. The research proposed for the mentored phase will take place in the exceptional environment of the National Human Genome Research Institute Division of Intramural Research. Dr. Elizabeth Nabel, a recognized leader in molecular genetics and vascular biology, and Dr. Aravinda Chakravarti, a leading expert in the genetics of complex cardiovascular traits, will mentor my scientific development. In addition, an advisory committee of highly accomplished genomic scientists will provide scientific and career guidance. The research plan integrates career development goals in 3 Specific Aims to: (1) test the hypothesis that vascular remodeling in response to arterial injury is, in part, genetically determined, by mapping the genetics of in-stent restenosis (ISR); (2) test the hypothesis that sequence variation in candidate susceptibility genes for ISR alters gene expression of these genes and other genes in related biologic pathways; and (3) test the hypothesis that candidate genes for ISR, as determinants of vascular injury responses, are associated with atherosclerosis, which is also characterized by adverse vascular remodeling. Aim 1 will be conducted during the mentored phase of this Award, to provide me with advanced training in genetic analysis of human subjects, with the goal of defining candidate susceptibility genes in the complex vascular disease, ISR. After transitioning to a faculty position with an independent laboratory, I plan to conduct the research proposed in Aims 2 and 3 using skills acquired during fellowship training to gather sufficient preliminary data during this phase to apply for further R01 funding. This program will develop the skills required to investigate the genetics of complex cardiovascular disease as an independent scientist. My goal is to become tenured faculty in a Division of Cardiology at an academic health center where my research will focus on cardiovascular genomics.

描述（由申请人提供）： 该提案描述了心血管基因组学学术生涯发展的五年计划。我在NIH完成了临床心脏病学研究和三年的博士后培训。现在，我将通过对复杂心血管疾病的基因组分析，扩展我在分析和解释基因组关联的无偏倚研究所需的分子，统计和流行病学原理方面的科学技能。在这个奖项的过程中，我计划过渡到独立，并建立在作为一个研究员完成的工作，调查血管重塑的遗传基础。为指导阶段提出的研究将在国家人类基因组研究所校内研究部的特殊环境中进行。分子遗传学和血管生物学领域公认的领导者Elizabeth Nabel博士和复杂心血管性状遗传学领域的领先专家Aravinda Chakravarti博士将指导我的科学发展。此外，一个由高度成就的基因组科学家组成的咨询委员会将提供科学和职业指导。研究计划将职业发展目标整合到3个具体目标中，以：（1）通过绘制支架内再狭窄（ISR）的遗传学图谱，检验动脉损伤后血管重塑部分由遗传决定的假设;（2）检验ISR候选易感基因的序列变异改变这些基因和相关生物学途径中其他基因的基因表达的假设;和（3）检验ISR候选基因作为血管损伤反应的决定因素与动脉粥样硬化相关的假设，动脉粥样硬化也以不利的血管重塑为特征。目标1将在该奖项的指导阶段进行，为我提供人类受试者遗传分析的高级培训，目标是定义复杂血管疾病ISR中的候选易感基因。在过渡到具有独立实验室的教师职位后，我计划使用在奖学金培训期间获得的技能进行目标2和3中提出的研究，以在此阶段收集足够的初步数据，以申请进一步的R 01资助。该计划将培养作为独立科学家调查复杂心血管疾病遗传学所需的技能。我的目标是成为一个学术健康中心的心脏病学部门的终身教师，我的研究将集中在心血管基因组学上。

项目成果

A genome-wide association study identifies a region at chromosome 12 as a potential susceptibility locus for restenosis after percutaneous coronary intervention.

一项全基因组关联研究将 12 号染色体上的一个区域确定为经皮冠状动脉介入治疗后再狭窄的潜在易感位点。

• DOI: 10.1093/hmg/ddr389
• 发表时间: 2011
• 期刊: Human molecular genetics
• 影响因子: 3.5
• 作者: Sampietro,MLourdes;Trompet,Stella;Verschuren,JeffreyJW;Talens,RudolfP;Deelen,Joris;Heijmans,BastiaanT;deWinter,RobbertJ;Tio,ReneA;Doevendans,PieterAFM;Ganesh,SanthiK;Nabel,ElizabethG;Westra,Harm-Jan;Franke,Lude;vand
• 通讯作者: vand