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（由适用提供）：该NRSA个体博士后奖学金的目的是帮助Flevaris博士作为心血管医学领域的物理科学家的发展，以及心脏纤维化研究的领导者。他和他的心态沃恩博士制定了一项多方面的培训计划，以基于他的医学和心脏病学背景，并增强他的科学研究能力。在此奖项期间，弗尔瓦里斯博士提出的提议通过1）旨在提高他对基础科学研究方法的理解的课程工作，2）与临床医生和其他教职员工的合作，3）培训其他体内和体外方法，以研究心脏病的机制，以及4）一项监督研究项目。这些重要经历中的每一个都将有助于支持他向独立调查员的职业过渡。该项目的总体科学目标是通过三个主要特定目的研究心肌细胞整联蛋白 - 摩 - 矩阵相互作用在心脏纤维化开发中的作用：1）在野生型小鼠中以及在野生型小鼠中执行损伤介导的心脏纤维化模型，并在小鼠中表现出年龄依赖性的伴有性心脏纤维化； 2）确定细胞外基质（ECM）混乱和心肌细胞整合素组成对心脏纤维化的影响； 3）定义特定ECM蛋白对体外心肌细胞整合素表达和信号传导的影响。该项目将在基础科学研究战略和写作以及集中的心态计划方面提供正规的学术培训，并将支持Flevaris博士的纵向发展成为一位熟练的临床和基础科学家。这个项目将通过支持与心脏纤维化基本机制有关的基本发现来实现国家卫生研究院的使命，其最终目的是提供新颖的治疗靶标和方法，以减少心血管疾病的大量公共卫生烧伤。从该项目中获得的知识将直接提高我们对心脏纤维化患者发育，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或类似赠款，进一步研究心血管疾病的分子机制。