Hippo and Wnt Signaling in Cardiac Regeneration

心脏再生中的 Hippo 和 Wnt 信号转导

• 批准号: 9887526
• 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/9887526
• 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; Family suidae; 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; prevent; protein transport; receptor; regenerative; repaired; response; response to injury; self-renewal; severe injury; single-cell RNA sequencing; unpublished works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.

这个R01应用程序将研究一种新的信号通路，Hippo通路