Function of GATA-6 in Vascular Smooth Muscle

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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)