Hippo and Wnt Signaling in Cardiac Regeneration

心脏再生中的 Hippo 和 Wnt 信号转导

• 批准号: 10063539
• 负责人: James F Martin
• 金额: $ 58.87万
• 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 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10063539
• 关键词: Acute; Address; Adult; Apoptosis; Binding; Binding Sites; Biological Assay; Biology; Blood Vessels; Cardiac; Cardiac Myocytes; Cause of Death; Cell Nucleus; Cells; Chromatin; Clinical; DNA Binding; DNA Damage; Data; Doxycycline; Endothelial Cells; Enhancers; Exclusion; Expression Profiling; Fibroblasts; Fibrosis; Functional disorder; Genes; Genetic Transcription; Genome; Genomics; Goals; Heart; Heart failure; Homeostasis; Human; Injury; Ligands; Mammals; Methods; Modeling; Molecular; Molecular Conformation; Mus; Myocardial Infarction; Myocardial Ischemia; Myocardium; Natural regeneration; Neonatal; Nuclear; Organ Size; Pathway interactions; Patients; Phosphorylation; Phosphotransferases; Property; Publishing; Pump; Reactive Oxygen Species; Regulation; Regulatory Pathway; Reporting; Secondary to; Signal Pathway; Signal Transduction; Survival Rate; Systolic heart failure; Technology; Testing; Tetanus Helper Peptide; Tissues; Transgenic Organisms; Transposase; Treatment Failure; United States; WNT Signaling Pathway; Work; angiogenesis; beta catenin; cardiac regeneration; cardiac repair; chromatin immunoprecipitation; cofactor; conditional knockout; gene therapy; genome editing; heart damage; heart dimension/size; improved; inhibitor/antagonist; innovation; insight; novel; porcine model; prevent; protein transport; receptor; regeneration potential; repaired; response; response to injury; self-renewal; severe injury; single-cell RNA sequencing; unpublished works

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 repair in a manner similar to the interaction in neonatal hearts. To determine whether an autonomous Wnt Hippo interaction occurs in heart muscle nuclei to control important genes and to investigate whether Hippo functions in a reversible manner. The project is conceptually and technically innovative. Concepts to be tested include new ideas in cardiomyocyte biology and cutting edge genome editing and interrogation 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.

该 R01 应用程序将研究一种新的信号传导途径，即 Hippo 途径， 哺乳动物心脏再生。长期目标是开发新的治疗方法 通过在成人心脏中产生新的心肌细胞来治疗心力衰竭的患者。这 该应用程序的目的是深入了解心脏的分子特性 受河马信号调节的组织。中心假设是河马 信号传导是一种负调节途径，可阻止心肌细胞再生 成年哺乳动物的心脏。具体目标是确定河马和 Wnt 通路以类似于相互作用的方式调节成人心脏修复 新生儿的心脏。确定 Wnt Hippo 自主相互作用是否发生在 心肌细胞核控制重要基因并研究河马是否 以可逆的方式发挥作用。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和前沿的新想法 基因组编辑和询问技术来解决假设。意义 之所以高，是因为没有治疗心肌细胞丢失引起的心力衰竭的方法。 设计产生新心肌细胞的方法非常重要。