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

• 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
• 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

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）： 该提案描述了一项为期五年的培训计划，以开发分子心脏病学学术生涯，因为它与调节RhoGap蛋白的调节内皮细胞分化，血管生成和胚胎发生有关。除两年的临床心脏病学培训外，首席研究员还完成了三年的分子心脏病学博士后培训，目前他符合心脏病学的资格。该计划提供了一个独特的机会，以基于主要研究者的临床和分子生物学专业知识，并将结构化学习，课程工作和实验室技术结合到一种多学科的方法中，以研究分子，基因组和生理性调节内皮细胞的分子调节，由p68RACGAP在Cam Patcherial of Cam Patcherial of Campations in the Intractial of Campations n of Campational of Dopation tho中，该教授的领导者是一定的。分化。为了增强培训，该计划已获得咨询委员会的专业知识，该咨询委员会由既定的研究人员组成具有分子生物学专业知识的科学和职业建议的专业知识，以及具有在细胞生物学，血管生成和目标失活基因领域具有广泛专业知识和经验的合作者的协助。拟议的研究将重点介绍P68RACGAP的作用，该研究通过其在体内相互作用与内皮细胞特异性转录因子（VEZFL）在调节内皮细胞分化，血管生成和胚胎发生中的作用。我们已经表明，p68racgap是一种Rac1特异性的Rhogap蛋白，可抑制体内内皮细胞毛细管组件。我们假设p68racgap是一种调节蛋白，对内皮细胞分化和血管生成至关重要，而靶向p68racgap基因的靶向缺失将导致胚胎发生扰动。该提案的总体目标是定义p68racGAP依赖信号调节对内皮细胞分化的生物学效应，确定p68racGAP在血管生成上的作用，并通过免疫性化的p68racgap敲除小鼠表征p68racgap敲除小鼠的表型，并分析靶向胚胎的胚胎胚胎胚胎的作用。北卡罗来纳大学 - 教堂山内医学系和卡罗来纳州心血管生物学中心为医师科学家提供了理想的培训环境，其多样化的资源，既定的研究人员并为年轻研究人员提供了支持。 （抽象的结尾）