The cellular basis of CCM gene function in development

发育过程中 CCM 基因功能的细胞基础

基本信息

批准号：
7455895
负责人：
KEVIN J WHITEHEAD
金额：
$ 13.47万
依托单位：
UNIVERSITY OF UTAH
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：
2006-07-01 至 2011-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7455895
关键词：
Address Advisory Committees Affect Alleles Arteries Award Biological Assay Blood Vessels Cardiology Cavernous Malformation Cell Adhesion Cell physiology Cells Cellular biology Cerebrum Clinical Sciences Coculture Techniques Collaborations Conditioned Culture Media Core Facility Cultured Cells Cytoplasmic Protein Data Defect Development Developmental Biology Doctor of Philosophy Embryo Endothelial Cells Endothelium Environment Essential Genes Event Faculty Family Family member Gene Expression Gene Silencing Gene Targeting Genes Genetic Genetic Markers Genetic Programming Germ Lines Germ-Line Mutation Growth Factor Histocompatibility Testing Human Human Pathology Impairment In Situ Hybridization Integrins Knock-out Knockout Mice Ligands Medicine Membrane Molecular Biology Morphology Mus Mutant Strains Mice Mutate Mutation Neuraxis Neurons Partner in relationship Pathway interactions Pattern Phenotype Physicians Play Portugal Recording of previous events Research Research Training Reverse Transcriptase Polymerase Chain Reaction Role Scientist Selectins Signal Transduction System Testing Time Tissues Transgenes Universities Utah Veins Venous Veterinary Medicine Work base capillary bed career cell type gene function malformation member migration mutant nestin protein notch protein paracrine professor programs promoter protein function receptor binding recombinase relating to nervous system response

项目摘要

DESCRIPTION (provided by applicant): This proposal outlines a 5-year plan for the career development of Kevin Whitehead to build upon his research training received as a Pfizer postdoctoral research fellow and to facilitate his transition to independence and excellence in the field of vascular developmental biology. Dean Li, MD, PhD, Associate Professor of Medicine, a recognized leader in the field of vascular developmental biology, will serve as sponsor. Additional scientific and career advice will be obtained from co-sponsor Guy Zimmerman, Professor of Medicine and chair of the program in Human Molecular Biology and Genetics (HMBG) and a recognized expert in vascular cell biology, integrins and selectins. This work will be done in collaboration with Douglas Marchuk, Associate Professor of Genetics at Duke University, and Antonio Duarte, Auxiliary Professor at the Faculty of Veterinary Medicine in Lisbon, Portugal. In addition, a scientific advisory committee will be formed to provide scientific and career advice. Previous work demonstrated an important role in arterial development for Ccm1, a gene responsible for a subset of CCM cases in humans. Proposed research will address the hypothesis that arterial development requires the expression of Ccm1, Ccm2 and Ccm3. Specific aims include: 1) Describe the first developmental role of CCM genes by studying null mutants. 2) Determine the cellular basis for vascular defects, by studying conditional mutants with neural or endothelial mutations of the CCM genes. 3) Describe the cellular basis of CCM gene function by examining the endothelial cell culture phenotype resulting from a lack of CCM gene expression in endothelial cells or adjacent neural cells. The University of Utah provides an ideal environment for the proposed research career award. The University of Utah has excellent core facilities and a rich history of gene targeting in mice. The Division of Cardiology has a strong commitment to developing young academic faculty, and the HMBG program is unique in acting as an interface between basic and clinical science and has provided an ideal environment for the professional development of physician scientists such as Dr. Whitehead.

描述（由申请人提供）：该提案概述了凯文·怀特黑德 (Kevin Whitehead) 职业发展的 5 年计划，以他作为辉瑞博士后研究员接受的研究培训为基础，并促进他在血管发育生物学领域向独立和卓越过渡。血管发育生物学领域公认的领导者、医学博士、哲学博士、医学副教授李院长将担任赞助商。其他科学和职业建议将从共同发起人 Guy Zimmerman 那里获得，他是医学教授、人类分子生物学和遗传学 (HMBG) 项目主席，也是血管细胞生物学、整合素和选择素方面的公认专家。这项工作将与杜克大学遗传学副教授 Douglas Marchuk 和葡萄牙里斯本兽医学院辅助教授 Antonio Duarte 合作完成。此外，还将成立一个科学咨询委员会，提供科学和职业建议。先前的工作证明了 Ccm1 在动脉发育中的重要作用，Ccm1 是人类 CCM 病例子集的基因。拟议的研究将解决动脉发育需要 Ccm1、Ccm2 和 Ccm3 表达的假设。具体目标包括： 1) 通过研究无效突变体来描述 CCM 基因的第一个发育作用。 2) 通过研究具有 CCM 基因神经或内皮突变的条件突变体，确定血管缺陷的细胞基础。 3) 通过检查由于内皮细胞或邻近神经细胞中缺乏 CCM 基因表达而导致的内皮细胞培养物表型，描述 CCM 基因功能的细胞基础。犹他大学为拟议的研究职业奖提供了理想的环境。犹他大学拥有优良的核心设施和小鼠基因靶向的丰富历史。心脏病学部坚定地致力于培养年轻的学术教师，HMBG 项目在充当基础科学和临床科学之间的桥梁方面具有独特的作用，并为怀特海德博士等医师科学家的专业发展提供了理想的环境。