Modulation of epigenetically controlled cardiac repair mechanisms by ethanol

乙醇调节表观遗传控制的心脏修复机制

• 批准号: 8997038
• 负责人: Alexander R. Mackie
• 金额: $ 13.15万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-10 至 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8997038
• 关键词: Acute; Acute myocardial infarction; Address; Advisory Committees; Affect; Alcohol consumption; Alcohols; Belief; Biological Phenomena; Bone Marrow; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cell physiology; Cells; Chicago; Chronic; Clinical; Consumption; Coronary heart disease; Data; Development; Doctor of Philosophy; Dose; Endothelial Cells; Epigenetic Process; Ethanol; Fingerprint; Gene Expression; Gene Expression Profile; Gene Targeting; Genes; Goals; Health; Heart; Histones; Human; Incidence; Injury; Institution; Investigation; Ischemia; Lead; MMP9 gene; Mediating; Medicine; Mentors; Modeling; Modification; Mus; Myocardial; Myocardial Infarction; Myocardial Ischemia; Myocardial tissue; Outcome; Patients; Pattern; Pharmacology; Play; Population; Post-Translational Protein Processing; Preventive Medicine; Process; Program Development; Recording of previous events; Recovery; Regenerative Medicine; Regulation; Research; Research Design; Research Institute; Research Proposals; Resources; Risk; Role; Science; Scientist; Severities; Stem cells; Testing; Tissues; Training; Training Programs; Universities; alcohol exposure; alcohol research; base; biomedical scientist; cardiac repair; career; cell type; chronic alcohol ingestion; design; drinking; epigenetic regulation; epigenome; epigenomics; experience; functional outcomes; heart cell; improved; in vivo; innovation; loss of function; mid-career faculty; mortality; novel; post-doctoral training; professor; programs; repaired; research study; skills; stem cell biology; survival outcome

DESCRIPTION (provided by applicant): This application describes a 5 year training program for the development of an independent academic career in the Biomedical Sciences. The PI completed his Ph.D. training in Pharmacology at Loyola University Chicago and additional post-doctoral training in Regenerative Medicine in the Feinberg Cardiovascular Research Institute (FCVRI) at Northwestern University. The FCVRI provides an ideal setting by incorporating expertise from diverse resources into customized programs in order to maximize the potential for trainees establishing a scientific niche from which a successful, independent academic career can be launched. This application will expand upon the PI's scientific and analytical skills through a unique integration of interdepartmental resources. This program will assess how chronic ethanol consumption modulates the endothelial epigenome to alter functional and survival outcomes following acute myocardial infarction (AMI). Dr. Raj Kishore (Associate Professor of Medicine) will mentor the PI's scientific development and does so as a recognized leader in the field of Regenerative Medicine with a formidable record of training academically successful independent scientists. Additionally, the program will enlist the expertise of Dr. Lifan Hou (Associate Professor of Preventative Medicine) and Dr. Gangjian Qin (Assistant Professor of Medicine) as co- mentors, who are both well-respected scientists within their respective fields. Lastly, several highly-regarded biomedical scientists will form a developmental advisory committee alongside an expert alcohol contributor (Dr. Elizabeth Kovacs) to provide scientific and career advice throughout the PI's development. The application focuses on how ethanol modulates the epigenomic programs in cell types involved in myocardial ischemic repair. Preliminary data reveals that chronic ethanol alters expression patterns of specific genes (i.e., eNOS and MMP9) in endothelial progenitor cells (EPCs): an important cell type involved in post-ischemic repair. Evidence shows that chronic ethanol consumption impacts cardiac function following an AMI and also alters various epigenetic marks in endothelial cells (ECs). Proposed experiments will utilize a chronic ethanol consumption model to explore cellular/epigenetic changes that manifest as altered outcomes following AMI. The specific aims include: 1) To determine why disparate levels of prior chronic ethanol consumption produce differential effects on cardiac function following AMI, 2) To investigate the mechanistic basis and functional impact of ethanol's modulation of the epigenomic fingerprint in CECs/EPCs, 3) What role does ethanol-mediated epigenetic regulation of MMP9 and eNOS expression play in EPC-mediated myocardial repair following AMI? This is the first mechanistic analysis of ethanol-induced epigenomic regulation in the heart and uses relevant models that mimic the circumstances of human patients.

描述（由申请人提供）：此申请描述了在生物医学科学领域发展独立学术生涯的5年培训计划。他在芝加哥洛约拉大学完成了药理学博士培训，并在西北大学范伯格心血管研究所（ffcvri）完成了再生医学博士后培训。FCVRI提供了一个理想的环境，将来自不同资源的专业知识整合到定制项目中，以最大限度地提高学员建立科学利基的潜力，从而启动成功的、独立的学术生涯。这个应用程序将扩展PI的科学和分析技能