Cardiomyocyte Integrin-Matrix Interactions Regulate Cardiac Fibrosis

心肌细胞整合素-基质相互作用调节心脏纤维化

基本信息

批准号：
9051073
负责人：
Panagiotis Flevaris
金额：
$ 6.2万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-03-01 至 2018-02-26
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9051073
关键词：
Academic Training Adhesions Adult Affect Aging Angiotensin II Applications Grants Architecture Area Autopsy Award Basic Science Cardiac Cardiac Myocytes Cardiology Cardiomyopathies Cardiovascular Diseases Cardiovascular system Cicatrix Clinical Clinical Investigator Award Collaborations Collagen Connective Tissue Data Deposition Development Diabetes Mellitus Elderly Environment Epidemic Exhibits Extracellular Matrix Extracellular Matrix Proteins Faculty Fellowship Fibroblasts Fibrosis Future Genes Genetic Goals Grant Health Heart Heart Diseases Homeostasis Human Immunohistochemistry In Vitro Incubated Individual Infusion procedures Injury Integrin beta3 Integrins Investigation Knowledge Laboratories Laminin Lead Matrix Metalloproteinases Mediating Medicine Mentors Mentorship Mission Modeling Molecular Molecular Profiling Mus Myocardial Myocardial Infarction Myocardial tissue Myocardium National Research Service Awards Obesity Outcome Pathologic Patient-Focused Outcomes Patients Physicians Plasminogen Plasminogen Activator Inhibitor 1 Population Prevalence Prevention Process Production Proteins Public Health Rattus Reperfusion Injury Research Research Methodology Research Personnel Research Project Grants Reverse Transcriptase Polymerase Chain Reaction Role Scientist Serine Protease Signal Transduction Staging System Tissues Training United States National Institutes of Health Ventricular Vitronectin Western Blotting Wild Type Mouse Writing age related base career constriction coronary fibrosis design experience heart cell improved in vivo innovation insight interstitial macrophage meetings member new therapeutic target novel overexpression patient population prognostic value response scaffold skills

项目摘要

DESCRIPTION (provided by applicant): The goal of this NRSA individual postdoctoral fellowship is to assist the development of Dr. Flevaris as a physician scientist in the field of cardiovascular medicine, and a leader in cardiac fibrosis research. He and his mentor, Dr. Vaughan, have developed a multifaceted training plan in order to build upon his clinical background in medicine and cardiology, and strengthen his scientific investigational abilities. During this award period, Dr. Flevaris proposes to develop additional skills through 1) coursework designed to improve his understanding of basic science research methodologies, 2) collaboration with clinicians and other faculty, 3) training in additional in vivo and in vitro approaches to study the mechanisms of cardiac disease, and 4) a supervised research project. Each of these vital experiences will help support his transition to a career as an independent investigator. The overall scientific objective of this project is to investigate the role of cardiomyocyte integrin-matrix interactions in the development of cardiac fibrosis through three primary specific aims: 1) To perform an injury-mediated cardiac fibrosis model in wild type mice and in mice that demonstrate age-dependent spontaneous cardiac fibrosis; 2) To determine the effect of extracellular matrix (ECM) disorganization and cardiomyocyte integrin composition on cardiac fibrosis; and 3) To define the effect of specific ECM proteins on cardiomyocyte integrin expression and signaling in vitro. This project will provide formal academic training in basic science research strategy and writing, as well as a focused mentorship plan, and will support Dr. Flevaris' longitudinal development into a proficient clinical and basic scientist. This project will meet the mission of the National Institute of Health by supporting basic discoveries related to the fundamental mechanisms of cardiac fibrosis, with the ultimate goal of providing novel therapeutic targets and approaches to reduce the significant public health burden of cardiovascular disease. The knowledge gained from this project will directly improve our understanding of the mechanisms underlying the development, progression, and clinical outcomes of patients with cardiac fibrosis. Dr. Flevaris plans to submit a Clinical Investigator Award application or similar grant using the results of this project, further investigating the molecular mechanisms of cardiovascular disease.

描述（由申请人提供）：该 NRSA 个人博士后奖学金的目标是协助 Flevaris 博士发展成为心血管医学领域的医师科学家以及心脏纤维化研究的领导者。 Vaughan 制定了一项多方面的培训计划，以巩固他在医学和心脏病学方面的临床背景，并加强他的科学研究能力。在获奖期间，Flevaris 博士建议通过以下方式培养额外的技能：1)旨在提高他对基础科学研究方法的理解的课程，2）与超级明星和其他教师的合作，3）研究心脏病机制的其他体内和体外方法的培训，以及4）一个监督研究项目。这些重要的经验将有助于支持他向独立研究者的职业生涯过渡，该项目的总体科学目标是通过三个主要具体目标来研究心肌细胞整合素-基质相互作用在心脏纤维化发展中的作用：1) 执行。一个在野生型小鼠和表现出年龄依赖性自发性心脏纤维化的小鼠中建立损伤介导的心脏纤维化模型；2) 确定细胞外基质 (ECM) 解体和心肌细胞整合素组成对心脏纤维化的影响；3) 确定该影响；该项目将提供基础科学研究策略和写作方面的正式学术培训，以及重点指导计划，并将支持 Flevaris 博士的研究。纵向发展成为一名熟练的临床和基础科学家。将通过支持与心脏纤维化基本机制相关的基本发现来履行美国国立卫生研究院的使命，最终目标是提供新的治疗靶点和方法，以减轻心血管疾病的重大公共卫生负担。该项目将直接提高我们对心脏纤维化患者的发展、进展和临床结果的机制的理解。Flevaris 博士计划使用该项目的结果提交临床研究者奖申请或类似的资助，进一步研究分子机制。心血管疾病。