p68RacGAP signaling in endothelial cell differentiation and angiogenesis

内皮细胞分化和血管生成中的 p68RacGAP 信号传导

基本信息

批准号：
7131792
负责人：
JULIUS EGEDE AITSEBAOMO
金额：
$ 12.56万
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：
2006
资助国家：
美国
起止时间：
2006-09-30 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7131792
关键词：
angiogenesis biological signal transduction cell differentiation cell growth regulation chorioallantoic membrane developmental genetics embryogenesis gene deletion mutation genetic regulation genetically modified animals guanosinetriphosphatase activating protein immunocytochemistry laboratory mouse phenotype tissue /cell culture transcription factor vascular endothelium

项目摘要

DESCRIPTION (provided by applicant): This proposal describes a five year training program for the development of an academic career in molecular cardiology as it pertains to regulation of endothelial cell differentiation, angiogenesis and embryogenesis by RhoGAP proteins. The principal investigator has completed three years of postdoctoral training in molecular cardiology in addition to a two-year clinical cardiology training, and he is currently board eligible in cardiology. This program provides a unique opportunity to build on the principal investigator's clinical and molecular biology expertise and to combine structured learning, course work and laboratory techniques into a multidisciplinary approach to studying the molecular, genomic and physiologic regulation of endothelial cell differentiation by p68RacGAP under the tutelage of Dr. Cam Patterson, Professor of Medicine who is internationally recognized as a leader in the field of endothelial cell differentiation. To enhance the training, the program has enlisted the expertise of an advisory committee that consists of established investigators with expertise in molecular biology for scientific and career advice, and the assistance of collaborators with extensive expertise and experience in the field of cell biology, angiogenesis, and targeted inactivation of genes. The proposed research will focus on the role of p68RacGAP, identified via its in vivo interaction with an endothelial cell-specific transcription factor (Vezfl), in regulation of endothelial cell differentiation, angiogensis and embryogenesis. We have shown that p68RacGAP is a Rac1-specific RhoGAP protein that inhibits endothelial cell capillary assembly in vivo. We hypothesize that p68RacGAP is a regulatory protein that is critical to endothelial cell differentiation and angiogenesis and that targeted deletion of p68RacGAP gene will lead to perturbation in embryogenesis. The overall objectives of this proposal are to define the biologic effect of p68RacGAP-dependent signal regulation on endothelial cell differentiation, determine the role of p68RacGAP on angiogenesis and to characterize the phenotype of p68RacGAP knockout mice and analyze targeted embryos for vascular and cardiac defects by immunohistochemical analysis and functional assays. The University of North Carolina-Chapel Hill Department of Internal Medicine and the Carolina Cardiovascular Biology Center provides an ideal training environment for physician-scientists by its diverse resources, established investigators, and support for young investigators. (End of Abstract)

描述（由申请人提供）：该提案描述了一个为期五年的培训计划，旨在发展分子心脏病学的学术生涯，因为它涉及 RhoGAP 蛋白对内皮细胞分化、血管生成和胚胎发生的调节。首席研究员除了两年的临床心脏病学培训外，还完成了三年的分子心脏病学博士后培训，目前具有心脏病学委员会资格。该项目提供了一个独特的机会，以主要研究者的临床和分子生物学专业知识为基础，并将结构化学习、课程工作和实验室技术结合到多学科方法中，以在 p68RacGAP 的指导下研究内皮细胞分化的分子、基因组和生理调节Cam Patterson 博士是医学教授，国际公认的内皮细胞分化领域的领导者。为了加强培训，该计划聘请了咨询委员会的专业知识，该委员会由具有分子生物学专业知识的资深研究人员组成，可提供科学和职业建议，并得到在细胞生物学、血管生成、以及基因的定向失活。拟议的研究将重点关注 p68RacGAP 在调节内皮细胞分化、血管生成和胚胎发生中的作用，通过其与内皮细胞特异性转录因子 (Vezfl) 的体内相互作用来鉴定。我们已经证明 p68RacGAP 是一种 Rac1 特异性 RhoGAP 蛋白，可抑制体内内皮细胞毛细血管组装。我们假设 p68RacGAP 是一种对内皮细胞分化和血管生成至关重要的调节蛋白，p68RacGAP 基因的靶向删除将导致胚胎发生的扰动。该提案的总体目标是确定 p68RacGAP 依赖性信号调节对内皮细胞分化的生物学效应，确定 p68RacGAP 对血管生成的作用，表征 p68RacGAP 敲除小鼠的表型，并通过免疫组织化学分析目标胚胎的血管和心脏缺陷分析和功能测定。北卡罗来纳大学教堂山分校内科和卡罗莱纳心血管生物学中心凭借其多样化的资源、成熟的研究人员以及对年轻研究人员的支持，为医师科学家提供了理想的培训环境。（摘要完）