Hippo and Wnt signaling in cardiac regeneration

Hippo 和 Wnt 信号在心脏再生中的作用

• 批准号: 9206179
• 负责人: James F Martin
• 金额: $ 50.2万
• 依托单位: TEXAS HEART INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-15 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9206179
• 关键词: Acute; Address; Adrenergic Agents; Adult; Binding; Biochemical; Biology; CRISPR/Cas technology; Cardiac; Cardiac Myocytes; Cardiac Output; Cause of Death; Cell Line; Cell Nucleus; Cessation of life; Chronic; Cicatrix; Clinical; DNA Binding; Data; Development; Event; Excision; Exclusion; Financial compensation; Functional disorder; Gene Targeting; Genes; Genetic; Genetic Transcription; Goals; Grant; Heart; Heart Rate; Heart failure; Infarction; Injury; Knock-in Mouse; Knowledge; Lead; Lysine; Measurable; Methods; Modification; Molecular; Myocardial Infarction; Myocardial Ischemia; Natural regeneration; Oxygen Consumption; Pathway interactions; Patients; Phosphorylation; Phosphotransferases; Post-Translational Protein Processing; Property; Publishing; Pump; Recovery; Regulation; Regulatory Pathway; Reporting; Residual state; Secondary to; Serine; Signal Pathway; Signal Transduction; Source; Survival Rate; System; Technology; Testing; Time; Tissues; Translations; Ubiquitination; United States; WNT Signaling Pathway; Work; base; cardiac regeneration; cardiogenesis; cofactor; effective therapy; experimental study; gain of function; genome editing; heart cell; heart dimension/size; heart function; improved; inhibitor/antagonist; innovation; insight; mortality; mutant; novel; prevent; protein protein interaction; public health relevance; repaired; self-renewal; sumo1 gene; transcription factor

 DESCRIPTION (provided by applicant): This R01 application will investigate a novel signaling pathway, the Hippo pathway, in mammalian heart regeneration. The long-term goal is to develop new treatments for patients with heart failure by generating new cardiomyocytes in the adult heart. The objectives of this application are to gain insight into molecular properties of cardiac tissue that are regulated by Hippo signaling. The central hypothesis is that Hippo signaling is a negative regulatory pathway that prevents cardiomyocyte regeneration in the adult mammalian heart. The specific aims are to determine whether the Hippo and Wnt pathways regulate adult heart regeneration in a manner similar to the interaction in heart development; to determine whether the sumoylation post-translation modification is an important mechanism in Yap regulation; and to determine whether Hippo functions in the context of a chronic scar after myocardial infarction. The project is conceptually and technically innovative. Concepts to be tested include new ideas in cardiomyocyte biology and cutting edge genome editing technologies to address hypotheses. The significance is high because there are no treatments for heart failure due to cardiomyocyte loss. Devising ways to generate new cardiomyocytes is highly significant.

 描述（由申请人提供）：本R01申请将研究哺乳动物心脏再生中的一种新型信号传导途径，即Hippo途径。长期目标是通过在成人心脏中产生新的心肌细胞来为心力衰竭患者开发新的治疗方法。本申请的目的是深入了解由Hippo信号调节的心脏组织的分子特性。核心假设是Hippo信号传导是一种负调控途径，可阻止成年哺乳动物心脏中的心肌细胞再生。具体的目的是确定是否海马和Wnt途径调节成人心脏再生的方式类似于心脏发育中的相互作用，以确定是否sumoylation翻译后修饰是一个重要的机制，在雅普调节，并确定是否海马功能的背景下，心肌梗死后的慢性疤痕。该项目在概念和技术上都具有创新性。待测试的概念包括心肌细胞生物学的新想法和解决假设的尖端基因组编辑技术。由于心肌细胞丧失导致心力衰竭尚无治疗方法，因此其意义很高。设计产生新的心肌细胞的方法是非常重要的。