The Role of Tuberin in Smooth Muscle Cell Proliferation

描述(由申请人提供)： 这是杰拉尔丁·芬莱博士申请导师临床科学家发展奖的申请，目的是继续研究Tuberin对雌激素反应中的平滑肌细胞生长的影响。初步研究表明，TSC2基因的蛋白产物tuberin参与调节雌激素的生长反应，而MAPK是这一反应的重要信号中间产物。对这些观察结果的进一步探索将为理解以平滑肌细胞增殖为特征的疾病的发病机制提供新的见解，如哮喘、高血压、动脉粥样硬化和淋巴管肌瘤病。芬利博士将在塔夫茨大学医学院新英格兰医学中心的巴里·范伯格博士和哈佛医学院布里格姆妇女医院的世界TSC基因遗传学专家大卫·克维特科夫斯基博士的实验室工作。新英格兰医学中心的雌激素受体细胞信号专家理查德·卡拉斯博士也将为芬利博士提供额外的咨询支持。每个机构的设施都将随时可用，并将大力鼓励参加课程和会议。她将每天与Fanburg博士和Kwiatkowski博士互动，同时在每个实验室花费时间，并将每季度与咨询委员会会面。拟开展的研究主要集中在以下几个方面：1)研究Tuberin对雌激素介导的血管平滑肌细胞生长的调节作用；2)研究tuberin对MAPK活性和MAPK功能的影响；3)研究Tuberin对雌激素受体功能的调节作用；4)研究Tuberin对雌激素调节的在体血管平滑肌细胞生长的影响。这些研究将使芬莱博士成为一名受过教育和熟练的分子生物学家，使她有机会完成和发表高质量的研究，并在她担任该机构工作人员的同时，在获得未来的独立研究奖方面具有竞争力。

DESCRIPTION (provided by applicant): This is an application for a Mentored Clinical Scientist Development Award for Dr. Geraldine Finlay to pursue research on the influence of tuberin on the control of smooth muscle cell growth in response to estrogen. Preliminary studies provide information that tuberin, the protein product of the TSC2 gene, is involved in regulating the growth response to estrogen and that MAP kinase is a vital signaling intermediate for this response. Further exploration of these observations will provide new insights into understanding the pathogenesis of diseases characterized by smooth muscle cell proliferation such as asthma, hypertension, atherosclerosis and lymphangioleiomyomatosis. Dr. Finlay will work in the laboratory of Dr. Barry Fanburg at the New England Medical Center, Tufts University School of medicine, who is an authority on smooth muscle biology and Dr David Kwiatkowski, a world expert in the genetics of TSC genes, at the Brigham and Women's Hospital, Harvard School of Medicine. Dr. Richard Karas, an expert in estrogen receptor cell signaling, at the New England Medical Center will also provide additional advisory support to Dr. Finlay. Facilities at each of the institutions will be readily available and participation in courses and conferences will be strongly encouraged. She will interact daily with Dr Fanburg and Dr. Kwiatkowski while spending time in each laboratory and will meet quarterly with an Advisory Committee. The proposed research will focus on the following specific aims: 1) To study the effects of tuberin on estrogen-mediated regulation of smooth muscle cell growth, 2)To assess the effects of tuberin on MAP kinase activation and MAP kinase function, 3)To investigate the effects of tuberin on the regulation of estrogen receptor function and 4) To study the effect of tuberin on estrogen-regulated vascular smooth muscle cell growth in vivo. These studies will allow Dr. Finlay to become educated and adept as a molecular biologist, give her the opportunity to complete and publish high quality research and to be competitive in acquiring a future independent research award while she assumes a staff position at this institution.