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Function of Notch Signaling in Vascular Smooth Muscle

Notch信号在血管平滑肌中的功能

基本信息

批准号：
7161738
负责人：
AARON PROWELLER
金额：
$ 13.33万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-02-01 至 2007-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7161738
关键词：
Adhesions Adult Advisory Committees Animals Apoptosis Arterial Disorder Attention Biology Blood Vessels CADASIL Cancer Center Cardiology Cardiovascular system Cell Differentiation process Cell physiology Cells Cerebrum Collaborations Complex Core Facility Critical Pathways Data Development Disease Dose Embryo Gene Activation Gene Expression Gene Targeting Genes Genetic Transcription Hematopoietic Homeostasis Human Indium Injury Introns Laboratories Lead Ligands Maintenance Mentors Molecular Mus Muscle function Mutation Myosin Heavy Chains Numbers Organ Pattern Pear Pennsylvania Phenotype Physicians Play Principal Investigator Process Reagent Regulation Research Resources Role Scientist Signal Transduction Site Smooth Muscle Smooth Muscle Myocytes Smooth Muscle Myosins Supervision Syndrome System Technology Tissues Training Training Programs Transcription Coactivator Transcriptional Regulation Transgenic Mice Universities Vascular Endothelium Vascular Smooth Muscle abstracting angiogenesis base career design migration mouse Smc1l1 protein mouse Smc1l2 protein myocardin notch protein programs promoter receptor response success

项目摘要

DESCRIPTION (provided by applicant): This proposal describes a 5-year training program designed to develop an academic career for the candidate in vascular biology. The research focuses on vascular smooth muscle cell (VSMC) differentiation and phenotypic modulation with emphasis on the role of cell signaling in these processes. The activities proposed rely on a collaborative program of study under co-supervision of two internationally recognized principal investigators, Drs. Michael S. Parmacek, an expert in transcriptional regulation of VSMCs, and Warren S. Pear, a leader in the field of Notch signaling. Together, the candidate will utilize both intellectual and proprietary resources from these laboratories with further guidance by an advisory committee of distinguished physicians and scientists. Participation in didactic courses and research seminars will enhance the educational success of the program. The research plan centers on a role for Notch signaling in the differentiation and function of VSMCs. These cells have the unique capacity to alter their phenotype from contractile to proliferative activity in response to vascular injury and in the setting of vasculoproliferative disorders. Notch signaling is a well-described modulator of cell differentiation, proliferation and apoptosis, and animals deficient in select Notch signaling components display disrupted vascular development and homeostasis. Preliminary studies reveal that Notch signaling modulates VSMC-specific gene expression leading to the hypothesis that Notch signaling has an important role in the phenotypic regulation of VSMCs. Accordingly, specific aims of this proposal are to (1) determine the molecular basis of Notch signaling-induced smooth muscle gene expression; (2) determine the impact of dysregulated Notch signaling in established SMC differentiation systems and in mature VSMCs; and (3) determine the effect of inhibiting SMC-specific, RBP-Jk-dependent Notch signaling in mice. The Molecular Cardiology Research Center and the Abramson Cancer Center of the University of Pennsylvania provide extensive resources, collaborations, core facilities and intellectual expertise. As such, this is an ideal setting for the candidate to acquire mentored training towards an independent career as a physician-scientist. (End of Abstract)

描述（由申请人提供）：