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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：
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
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/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

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）：