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: 7292709
• 负责人: JULIUS EGEDE AITSEBAOMO
• 金额: $ 12.86万
• 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/7292709
• 关键词: Advisory Committees; Atherosclerosis; Biological Assay; Biology; Blood Circulation; Blood Vessels; Blood capillaries; Capillary Endothelial Cell; Cardiology; Cardiovascular system; Cell Differentiation process; Cell Shape; Cellular biology; Classification; Clinical; Complementary DNA; Congenital Heart Defects; Cornea; Critical Pathways; Cues; Defect; Development; Disease Outcome; Embryo; Embryonic Development; Endothelial Cells; Endothelin-1; Environment; Event; Gene Deletion; Gene Silencing; Genes; Genomics; Goals; Hindlimb; In Vitro; Internal Medicine; Ischemia; Knockout Mice; Laboratories; Lead; Learning; Libraries; Medicine; Messenger RNA; Modeling; Molecular; Molecular Biology; Mus; Neoplasm Metastasis; North Carolina; Organ; Oryctolagus cuniculus; Pattern; Pattern Formation; Phase; Phenotype; Physicians; Physiological; Play; Porifera; Portraits; Principal Investigator; Process; Program Development; Proteins; Regulation; Research; Research Personnel; Resources; Role; Scientist; Signal Pathway; Signal Transduction; Staging; Structure; System; Techniques; Testing; Tissues; Training; Training Programs; Transcriptional Activation; Tube; Universities; Vascular Endothelium; Work; Zinc Fingers; abstracting; angiogenesis; base; capillary; career; cell motility; cell type; chorioallantoic membrane; day; experience; genetic regulatory protein; in vivo; interdisciplinary approach; matrigel; migration; novel; post-doctoral training; postnatal; professor; programs; promoter; research study; rho GTPase-activating protein; subcutaneous; transcription factor; vasculogenesis; yeast two hybrid system

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、课程作业和实验室技术结合到多学科方法中，在国际公认的内皮细胞领域领导者医学教授 Cam Patterson 博士的指导下，研究 p68RacGAP 对内皮细胞分化的分子、基因组和生理调节。 差异化。为了加强培训，该项目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，提供科学和职业建议，并由在细胞生物学、血管生成和基因靶向失活领域拥有丰富专业知识和经验的合作者提供帮助。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和功能测定来分析目标胚胎的血管和心脏缺陷。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）