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Role of hemodynamics and ErbB signaling in cardiac trabeculation

血流动力学和 ErbB 信号在心脏小梁形成中的作用

基本信息

批准号：
8598276
负责人：
Jiandong Liu
金额：
$ 24.9万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-01 至 2016-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8598276
关键词：
Advisory Committees Apical Architecture Area Biochemistry Biological Models Biology Biophysics Blood flow California Cardiac Cardiac Myocytes Cardiomyopathies Cell Shape Cell physiology Cells Complex Data Deterioration Development Due Process Embryonic Development Endocardium Event Exhibits Failure Foundations Future Genetic Goals Heart Heart Diseases Heart Ventricle Link Mediating Mentors Mentorship Modeling Molecular Morphogenesis Myocardial Myocardium Pathway interactions Process Research Research Personnel Research Proposals Resolution Role San Francisco Scientist Shapes Signal Pathway Signal Transduction Structure Testing Time Training Universities Ventricular Ventricular Function Work Zebrafish abstracting career development cell motility constriction developmental disease hemodynamics improved migration muscular structure notch protein professor programs receptor response shear stress spatiotemporal tool

项目摘要

Project Summary/Abstract This proposal describes a five-year career development program whose goal is to prepare Dr. Jiandong Liu for a role as an independent investigator. This program will promote his career development by providing expertise in molecular and developmental cardiac biology. The principal guidance will be provided by the mentor, Dr. Didier Stainier, Professor of Biochemistry & Biophysics at the University of California, San Francisco. He is an expert in cardiac development and has a long record of training independent scientists. The training plan includes structured mentorship with an advisory committee, formal coursework, and a research program which will provide thorough training in molecular and developmental cardiac biology. In his preliminary studies, Dr. Jiandong has developed and validated a set of tools to be used to study cardiac morphogenesis in zebrafish. He has used these tools to explore the role for hemodynamic and ErbB signaling in cardiac trabeculation, a critical morphogenetic process that optimizes the internal structure of the cardiac ventricle for efficient conduction and contraction. This work has demonstrated 1) that the initiation of trabeculation is regulated by blood flow in a process that likely requires Notch signaling, and 2) ErbB2 cell-autonomously regulates cardiomyocyte migration to form cardiac trabeculae. In the research proposal, Dr. Jiandong will build on these findings to test the hypotheses that (1) activation of Notch signaling by blood flow induces neuregulin1 (nrg1) expression in the endocardium, and (2) Nrg1 activates its ErbB receptors in the myocardium to initiate trabeculation by causing cardiomyocyte apical constriction. He will begin by carefully assessing cell architecture, cell shape changes and cell migration during cardiac trabeculation. He will then perform detailed functional studies to define the regulatory networks that link flow and shear stress to long-term structural changes in the heart, an area of fundamental importance for understanding both developmental disorders of heart formation as well as many forms of acquired heart disease. In addition, this work will provide a foundation for future studies on cardiac trabeculation to be carried out by Dr. Jiandong when he becomes an independent investigator.

项目总结/文摘