The identification of endocardial regulatory elements in cardiac regeneration

项目总结/摘要 本建议书描述了罗兰S博士的五年职业发展计划。吴在角色 首席调查员吴博士是心血管研究所的助理临床教授， 加州大学旧金山弗朗西斯科内科心脏病科。这 工作将集中在心脏再生的基因调控，并将建立在吴博士的背景，心脏 心血管疾病的发展和遗传模型。他的目标是确定 作为对心脏损伤的内皮素反应和心脏再生的内皮素支持的基础。 在这份职业发展计划中，心血管发育和基因专家Brian Black博士 法规，将提供吴博士的工作的主要指导。额外的指导将由一个 一组世界级的专家，包括心脏再生领域的领导者（顾问肯尼斯·波斯，杜克）， 转化医学（顾问Deepak Srivastava，UCSF）和计算生物学（顾问凯瑟琳 Pollard，UCSF）。在UCSF的环境是杰出的，在各个领域的领先专家。武博士的 培训计划包括重点辅导和教学课程参与和会议演示 指导，指导。 吴博士的建议旨在研究内皮细胞对心脏损伤的反应时的基因调控。 再生他通过一系列强大而新颖的技术来实现这一点：1）增强剂 用于快速增强子鉴定的条形码系统，和2）用于遗传筛选的快速遗传编辑管道。 目的1鉴定和表征对心脏损伤和再生有反应的内皮素增强剂。目的2 定义了参与内分泌基因调控的转录网络和内分泌对 心脏损伤和再生。这项工作将利用高通量和详细的转基因分析 在斑马鱼和老鼠身上，利用每个系统的优势。此外，这项工作将 利用分子生物学和生物信息学方法预测再生过程中的关键调控元件 增强子，这些预测将在斑马鱼和小鼠试验中得到验证。 吴博士的职业发展奖提案包括一个有前途的候选人， 调查，世界一流的指导，并在一个优秀的环境严格的培训计划。结果 这项工作提供：1）直接解决因果关系的直接新的生物学见解，2）基础 长期独立的项目，以剖析调节心脏再生和心脏 对伤害的反应。这项工作将为罗兰吴博士作为一个独立的工作奠定基础 调查员

PROJECT SUMMARY/ABSTRACT This proposal describes a five-year career development program for Dr. Roland S. Wu in the role of principal investigator. Dr. Wu is an Assistant Clinical Professor at the Cardiovascular Research Institute and the Division of Cardiology, Department of Internal Medicine at University of California San Francisco. This work will focus on gene regulation in cardiac regeneration and will build upon Dr. Wu’s background in cardiac development and genetic models of cardiovascular disease. His objective is to determine the mechanisms underlying the endocardial response to cardiac injury and endocardial support of cardiac regeneration. In this career development plan, Dr. Brian Black, an expert in cardiovascular development and gene regulation, will provide the principal guidance for Dr. Wu’s work. Additional mentorship will be provided by a group of world-class experts that include leaders in cardiac regeneration (consultant Kenneth Poss, Duke), translational medicine (advisor Deepak Srivastava, UCSF), and computational biology (advisor Katherine Pollard, UCSF). The environment at UCSF is outstanding with leading experts in a variety of fields. Dr. Wu’s training plan includes focused tutorials and didactic coursework participation and presentation at conferences and mentored guidance with manuscript and grant preparation. Dr. Wu’s proposal aims to study gene regulation in endocardium as it responds to injury in cardiac regeneration. He approaches this through a combination of powerful and novel techniques: 1) an enhancer barcoding system for rapid enhancer identification, and 2) a rapid genetic editing pipeline for genetic screening. Aim 1 identifies and characterizes endocardial enhancers responsive to cardiac injury and regeneration. Aim 2 defines the transcriptional networks involved in endocardial gene regulation and the endocardial response to cardiac injury and regeneration. This work will make use of high throughput and detailed transgenic analyses in the zebrafish and in the mouse, taking advantage of the strengths of each system. Additionally, this work will use molecular biology and bioinformatics approaches to predict key regulatory elements in regeneration enhancers, and those predictions will be validated in zebrafish and mouse assays. Dr. Wu’s Career Development Award proposal comprises a promising candidate, impactful scientific investigation, world-class mentorship, and a rigorous training plan in an outstanding environment. The results of this work provide: 1) immediate new biological insights that directly address causality, and 2) a foundation for long-term independent program to dissect the mechanisms regulating cardiac regeneration and the cardiac response to injury. This work will provide a foundation for Dr. Roland Wu’s work as an independent investigator.