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Role of MicroRNA-499 in the Heart

MicroRNA-499 在心脏中的作用

基本信息

批准号：
8238402
负责人：
Joseph T Shieh
金额：
$ 12.54万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-15 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8238402
关键词：
Address Advisory Committees Animal Disease Models Biology Cardiac Cardiac Myocytes Cardiomyopathies Cardiovascular Diseases Cardiovascular system Characteristics Commit Committee Members Complement Data Development Developmental Biology Disease Environment Ethics Failure Fishes Fostering Functional RNA Functional disorder Gene Expression Gene Expression Profile Gene Expression Regulation Genes Genetic Goals Heart Heart Diseases Heart failure Human In Vitro Individual Institutes Introns Lead Link Measures Mediator of activation protein Mentors Messenger RNA MicroRNAs Mus Myocardial Myosin ATPase Myosin Heavy Chains Pathogenesis Pathway interactions Pattern Pediatrics Phenotype Physicians Play Predisposition Regulation Regulatory Pathway Research Research Personnel Research Training Role Scientist Stress Testing Time Training Transgenic Mice Ventricular career development design human disease in vivo interest mouse model myogenesis novel overexpression pediatric department pressure programs research study

项目摘要

DESCRIPTION (provided by applicant): This proposal describes a 5-year-long career development program whose goal is to prepare Dr. Joseph Shieh for a role as an independent investigator. This program will promote his career development by building on his background in genetics and pediatrics by providing expertise in developmental biology. The principal guidance will be provided by the mentor, Dr. Deepak Srivastava, director of the Gladstone Institute for Cardiovascular disease at UCSF. He is a recognized leader in cardiac development and has a record of training independent scientists. The project advisory committee members (Dr. Michael McManus, an expert on microRNA biology; Dr. Didier Stainier, an expert in cardiovascular genetics; and Dr. Robert Nussbaum, an expert in mouse models of human disease) will provide further training. The research program will address heart failure and the potential to alter heart failure by controlling the gene expression changes that characterize failure. The hypothesis is that the small non-coding RNAs called microRNAs play a key regulatory role in heart failure, and Dr. Shieh has identified one of the most highly enriched microRNAs in the human heart and determined that it is important in myogenesis. He developed a mouse model that alters the microRNA level in the heart and found that the mice develop cardiomyopathy. The microRNA triggers characteristic gene expression patterns that are seen in heart failure, suggesting this microRNA is controlling these pathways. In this project, the function of mir-499 in the heart will be assessed in three aims: 1) Dr. Shieh will determine the expression patterns of mir-499 and specific myosin genes in the heart to assign the microRNA to a specific gene regulatory pathway. 2) He will determine whether mir-499 levels exacerbate heart failure in animal models of disease. 3) He will determine the pathway by which mir-499 exerts its regulatory role in heart failure. Research training will be complemented by a formal didactic program in developmental biology, genetics, and ethics. The UCSF Pediatrics Department is committed to Dr. Shieh's career development. UCSF and Gladstone provide an outstanding environment for training independent physician scientists, promoting collaborative research and fostering individual scientific development.

描述（由申请人提供）：本提案描述了一个为期5年的职业发展计划，其目标是准备博士约瑟夫谢作为一个独立的调查员的作用。该计划将通过提供发育生物学方面的专业知识，以他在遗传学和儿科学方面的背景为基础，促进他的职业发展。主要的指导将由导师，加州大学旧金山分校格莱斯顿心血管疾病研究所所长Deepak Srivastava博士提供。他是心脏发展领域公认的领导者，并有培训独立科学家的记录。项目咨询委员会成员（微RNA生物学专家Michael McManus博士、心血管遗传学专家Didier Mackier博士和人类疾病小鼠模型专家Robert Nussbaum博士）将提供进一步培训。该研究计划将解决心力衰竭和通过控制表征心力衰竭的基因表达变化来改变心力衰竭的潜力。该假说认为，称为microRNA的小非编码RNA在心力衰竭中起着关键的调节作用，Shieh博士已经确定了人类心脏中最高度富集的microRNA之一，并确定它在肌生成中很重要。他开发了一种小鼠模型，改变了心脏中的microRNA水平，并发现小鼠患上了心肌病。microRNA触发了心力衰竭中观察到的特征性基因表达模式，表明这种microRNA控制着这些途径。在这个项目中，mir-499在心脏中的功能将从三个方面进行评估：1）Shieh博士将确定mir-499和特定肌球蛋白基因在心脏中的表达模式，以将microRNA分配给特定的基因调控途径。2)他将在动物疾病模型中确定mir-499水平是否会加剧心力衰竭。3)他将确定mir-499在心力衰竭中发挥调节作用的途径。研究培训将通过发育生物学，遗传学和伦理学的正式教学计划进行补充。UCSF儿科致力于Shieh博士的职业发展。UCSF和Gladstone为培养独立的医生科学家，促进合作研究和促进个人科学发展提供了出色的环境。