Deciphering the role of Notch signaling in zebrafish heart regeneration

破译Notch信号在斑马鱼心脏再生中的作用

• 批准号: 9041018
• 负责人: CAROLINE E BURNS
• 金额: $ 43.5万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9041018
• 关键词: Adult; Cardiac; Cardiac Myocytes; Cell Cycle Arrest; Cell physiology; ChIP-seq; Chromatin; Clinical; Collaborations; Complement; DNA Damage; Data; Data Set; Endocardium; Epicardium; Epigenetic Process; Epithelium; Excision; Exhibits; Fibrosis; Fishes; Gene Expression; Genes; Goals; Health; Heart; Heart failure; Histones; Human; Injury; Laboratories; Learning; Mitogens; Modeling; Molecular Profiling; Myocardial; Myocardial Infarction; Myocardium; Natural regeneration; Notch Signaling Pathway; Outcome; Paracrine Communication; Pathway interactions; Patient-Focused Outcomes; Phenotype; Production; Publishing; Reporting; Resolution; Role; Sequence Analysis; Signal Transduction; Testing; Therapeutic; Tissues; Transcriptional Activation; Transgenic Organisms; Vertebrates; Zebrafish; base; cardiac regeneration; demethylation; design; experience; gain of function; genome-wide; improved; injured; innovation; insight; loss of function; new growth; notch protein; novel; novel strategies; novel therapeutic intervention; novel therapeutics; paracrine; prevent; promoter; regenerative; repaired; response to injury; tool

 DESCRIPTION (provided by applicant): Novel therapeutic strategies for stimulating regeneration of human heart muscle would significantly improve clinical outcomes for patients experiencing a heart attack. In contrast to humans, adult zebrafish naturally regenerate their heart muscle following injury. Our lab recently discovered that the Notch signaling pathway becomes activated following cardiac injury in zebrafish and is required for stimulating growth of new cardiac muscle. The goal of this application is to gain new mechanistic insight into how Notch stimulates heart regeneration in fish with the long-term goal of informing new therapeutic strategies for redirecting or repurposing activated Notch for clinical benefit in humans.

 描述（由申请人提供）：刺激人类心肌再生的新型治疗策略将显著改善心脏病发作患者的临床结局。与人类不同，成年斑马鱼在受伤后会自然再生心肌。我们的实验室最近发现，Notch信号通路在斑马鱼心脏损伤后被激活，并且是刺激新心肌生长所必需的。本申请的目标是获得Notch如何刺激鱼类心脏再生的新机制见解，长期目标是为重新定向或重新利用激活的Notch以获得人类临床益处提供新的治疗策略。