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）： 该建议描述了一个为期五年的心血管基因组学学术生涯的计划。我已经完成了NIH的临床心脏病学研究金和三年的博士后培训。我现在将通过对复杂心血管疾病的基因组分析进行分析和解释基因组关联的分析和解释所必需的分子，统计和流行病学原理的科学技能。在此奖项的过程中，我计划过渡到独立性并以作为同伴完成的工作为基础，以调查血管重塑的遗传基础。提出的指导阶段的研究将在国家人类基因组研究所内壁内研究部的特殊环境中进行。伊丽莎白·纳​​贝尔（Elizabeth Nabel）博士是分子遗传学和血管生物学的公认领导者。此外，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。该研究计划将职业发展目标纳入了3个特定目的：（1）检验以下假设：响应动脉损伤的血管重塑部分是通过映射遗传学的遗传学（ISR）（ISR）； （2）检验以下假设：ISR的候选易感基因的序列变异会改变相关生物学途径中这些基因和其他基因的基因表达； （3）检验以下假设：ISR的候选基因作为血管损伤反应的决定因素与动脉粥样硬化有关，该假设也具有不良血管重塑的特征。 AIM 1将在该奖项的指导阶段进行，以为我提供对人类受试者的遗传分析的高级培训，目的是定义复杂血管疾病中的候选敏感性基因ISR。在通过独立实验室过渡到教师职位后，我计划在AIMS 2和3中使用奖学金培训期间获得的技能在此阶段收集足够的初步数据，以申请进一步的R01资金。该计划将发展研究复杂心血管疾病的遗传学所需的技能。我的目标是成为学术健康中心心脏病学系的终身教师，我的研究将重点放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