Function of GATA-6 in Vascular Smooth Muscle

描述（由申请人提供）： 该提案描述了一个为期5年的培训计划，以发展血管生物学的研究事业。 该计划旨在让申请人获得分子和细胞生物学方面的额外培训，以补充其先前在转化研究和小鼠心血管系统生理分析方面的培训。 研究领域将是血管平滑肌细胞（VSMC）分化和表型调节的转录调控，这是心血管科学和临床心脏病学的一个重要领域。 Michael Parmacek博士是这一领域的国际公认专家，他将与一个由杰出的医生科学家组成的咨询委员会一起指导申请人的科学发展沿着。 该计划将包括一系列教学课程，研究研讨会和旨在加强申请人科学发展的协作互动。 该研究计划将集中于转录因子加塔-6在VSMCs中的功能。 其他加塔转录因子在调节细胞类型分化和增殖中起关键作用。 博士Parmacek的实验室先前已经证明，加塔-6是胚胎发育期间内脏内胚层正常形成所必需的;然而，其在VSMC中的精确功能尚未确定。 本提案的重点将是确定加塔-6在调节VSMC表型中的作用。 具体目标是：1）检查加塔-6在体外调节VSMC增殖和存活中的作用; 2）评价加塔-6在体外调节VSMC细胞-细胞和细胞-基质相互作用中的作用;和3）确定加塔-6在VSMC分化和血管发育中的体内作用。 宾夕法尼亚大学的分子心脏病学研究中心拥有一群充满活力的心血管科学家和独特的核心实验室，设施和合作者基础设施，使其成为一个理想的环境，申请人可以获得启动独立职业所需的科学专业知识作为医生科学家。 (End摘要）

DESCRIPTION (provided by applicant): This proposal describes a 5-year training program to develop an investigative career in vascular biology. The program is designed for the applicant to obtain additional training in molecular and cellular biology to complement his prior training in translational research and in the physiologic analysis of the cardiovascular system of mice. The field of research will be the transcriptional regulation of vascular smooth muscle cell (VSMC) differentiation and phenotypic modulation, an area of significant importance to cardiovascular science and clinical cardiology. Dr. Michael Parmacek, an internationally recognized expert in this field, will mentor the applicant's scientific development along with an advisory committee of distinguished physician-scientists. The program will feature a series of didactic courses, research seminars, and collaborative interactions designed to enhance the applicant's scientific development. The research plan will focus on the function of the transcription factor GATA-6 in VSMCs. Other GATA transcription factors play critical roles in regulating cell-type differentiation and proliferation. Dr. Parmacek's lab has previously demonstrated that GATA-6 is required for normal formation of the visceral endoderm during embryonic development; however, its precise function in VSMCs has not been determined. The focus of this proposal will be to determine the role of GATA-6 in regulating VSMC phenotype. The specific aims will be: 1) to examine the role of GATA-6 in regulating VSMC proliferation and survival in vitro; 2) to evaluate the role of GATA-6 in regulating VSMC cell-cell and cell-matrix interactions in vitro; and 3) to determine the in vivo role of GATA-6 in VSMC differentiation and vascular development. The Molecular Cardiology Research Center at the University of Pennsylvania houses a vibrant group of talented cardiovascular scientists and a unique infrastructure of core laboratories, facilities, and collaborators that make it an ideal setting in which the applicant can acquire the scientific expertise required to launch an independent career as a physician-scientist. (End of Abstract)