Hippo and Wnt Signaling in Cardiac Regeneration

心脏再生中的 Hippo 和 Wnt 信号转导

• 批准号: 10551317
• 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 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10551317
• 关键词: Acute; Address; Adult; Binding; Binding Sites; Biological Assay; Biology; Blood Vessels; Cardiac; Cardiac Myocytes; Cause of Death; Cell Nucleus; Cells; Chromatin; Clinical; Communication; 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; Inhibition of Apoptosis; 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; Proliferating; 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; 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potential; repaired; response; response to injury; self-renewal; severe injury; single-cell RNA sequencing; unpublished works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.

此R01应用程序将研究一个新颖的信号通路，河马途径 哺乳动物心脏再生。长期目标是为 通过在成人心脏中产生新的心肌细胞来患有心力衰竭的患者。这 此应用的目标是洞悉心脏的分子特性 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，可防止心肌细胞再生 成年哺乳动物心脏。具体目的是确定河马和是否是否 Wnt途径以类似于相互作用的方式调节成人心脏修复 新生儿的心。确定自动wnt Hippo相互作用是否发生在 心肌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是创新的。 要测试的概念包括心肌细胞生物学和尖端的新想法 基因组编辑和审问技术以解决假设。意义 之所以很高，是因为由于心肌细胞丧失而没有治疗心力衰竭的治疗方法。 设计产生新的心肌细胞的方法非常重要。

项目成果

Gene therapy knockdown of Hippo signaling induces cardiomyocyte renewal in pigs after myocardial infarction.

• DOI: 10.1126/scitranslmed.abd6892
• 发表时间: 2021-06-30
• 期刊: Science translational medicine
• 影响因子: 17.1

Single nucleus transcriptome of a "Super RV" shows increased insulin and angiogenesis signaling.

“超级 RV”的单核转录组显示胰岛素和血管生成信号增加。

• DOI: 10.1101/2023.11.28.569092
• 发表时间: 2024
• 期刊: bioRxiv : the preprint server for biology
• 作者: Turaga,Diwakar;Li,Xiao;Zhao,Yi;Tsai,Chang-Ru;Moreira,Axel;Hickey,Edward;Adachi,Iki;Martin,James
• 通讯作者: Martin,James

Hippo signaling in cardiac fibroblasts during development, tissue repair, and fibrosis.

心脏成纤维细胞在发育、组织修复和纤维化过程中的 Hippo 信号传导。

• DOI: 10.1016/bs.ctdb.2022.02.010
• 发表时间: 2022
• 期刊: Current topics in developmental biology
• 作者: Tsai,Chang-Ru;Martin,JamesF
• 通讯作者: Martin,JamesF

The cell-autonomous and non-cell-autonomous roles of the Hippo pathway in heart regeneration.

• DOI: 10.1016/j.yjmcc.2022.04.018
• 发表时间: 2022-05
• 期刊: Journal of molecular and cellular cardiology
• 影响因子: 5
• 作者: Shijie Liu;R. Li;James F. Martin

Predicting unrecognized enhancer-mediated genome topology by an ensemble machine learning model.

通过集成机器学习模型预测未识别的增强子介导的基因组拓扑

• DOI: 10.1101/gr.264606.120
• 发表时间: 2020-12
• 期刊: Genome research
• 影响因子: 7
• 作者: Tang L;Hill MC;Wang J;Wang J;Martin JF;Li M
• 通讯作者: Li M