Bone Morphogenetic Proteins in Arterial Remodeling

描述(由申请人提供)： 这份有指导的K08建议书描述了为博士提供的5年培训计划。 古兹曼在血管领域向科学独立的转变 生物学。应聘者是外科系的助理教授 和细胞生物学。他现在将扩展他的科学技能和知识 基地通过与布里吉德·L·霍根博士的多学科互动 我们细胞生物系成员和理查德·胡佛博士，来自 病理学系和范德比尔特血管生物学主任 培训计划。古兹曼博士还得到了一位顾问的帮助。 -备受尊敬的科学家委员会，他们将提供科学和 职业建议。他们包括Jeffrey Balser博士、Barbara Meyrick博士和Dr. 道格拉斯·沃恩。 细胞生物学系为此次培训提供了理想的环境 程序。它结合了来自广泛学科的专业知识，并具有 可用于支持年轻教职员工的广泛资源。在……里面 除了直接在霍根博士的实验室工作外，古兹曼博士还将 有专门的实验室空间，离霍根博士的实验室很近 在一条属于细胞生物系的实验室走廊里。 古兹曼得到了他的科长和部门主席的全力支持 期间，他将75%的时间用于追求学术研究目标 获奖期。 古兹曼博士的近期目标是获得必要的培训和经验 成为一名独立的科学家。研究计划的重点是 骨形态发生蛋白在病理性动脉重塑中的作用这 细胞外信号蛋白家族属于转化生长因子-β超家族 而且它在血管疾病中的作用还没有确定。背景 初步数据表明，这些蛋白质可能是重要的调节因子。 通过其对血管平滑肌细胞迁移和再狭窄的影响来抑制再狭窄 扩散。根据他的初步数据，古兹曼博士假设 BMP受体可能是基因导向策略控制的理想靶点 肠粘膜增生症。具体目标包括：1)刻画时间 BMP在病理性动脉中的表达过程及细胞分布 小鼠的重塑。2)确定剪应力在诱导中的作用 体外内皮骨形成蛋白4的表达。3)评价IA型骨形态发生蛋白的效果 和IB受体激活在损伤诱导的SMC增殖和心肌损伤中的作用 体内蓄积。4)检测骨形态发生蛋白IA和IB受体的作用 激活SMC在体外的迁移、侵袭和增殖。按顺序 为了实现这些具体目标，古兹曼博士勾勒出了自己的研究生涯 发展计划，包括在实验室的重点培训期 霍根博士以及相关领域的课程工作。在这段时间里，他将 学会使用原位杂交和双重杂交技术 免疫荧光染色。他还将学习基本技术 参与了转基因和基因敲除小鼠品系的开发。Dr。 古兹曼的长期目标是为我们的 对病理性动脉重塑的认识。预计在此期间 在这个获奖期内，古兹曼博士将朝着成为一名 独立的科学调查员。

DESCRIPTION (provided by applicant): This Mentored K08 proposal describes a 5 year training program for Dr. Guzman's transition to scientific independence in the field of vascular biology. The candidate is an Assistant Professor in the Department of Surgery and Cell Biology. He will now expand on his scientific skills and knowledge base through a multidisciplinary interaction with Dr. Brigid L Hogan, a senior member of our Department of Cell Biology and Dr. Richard Hoover, from the Department of Pathology and the director of the Vanderbilt Vascular Biology Training Program. Dr. Guzman has also enlisted the help of an advisory committee of-highly-respected scientists who will provide scientific and career advice. They include Dr. Jeffrey Balser, Dr. Barbara Meyrick and Dr. Douglas Vaughan. The Department of Cell Biology provides an ideal environment for this training prograrn. It incorporates expertise from a broad array of disciplines and has extensive resources that can be used to support young faculty members. In addition to working directly in the laboratory of Dr. Hogan, Dr. Guzman will have a dedicated lab space that is located in close proximity to Dr. Hogan's lab and in a corridor of labs belonging to the Department of Cell Biology. Guzman has the full support of his Division Chief and Departmental Chair to devote 75 percent of his time to pursuing his academic research goals during the award period. Dr. Guzman's immediate goal is to obtain the training and experience necessary to become an independent scientist. The research plan focuses on the role of the Bone Morphogenetic Proteins (BMPs) in pathologic arterial remodeling. This family of extracellular signaling proteins belongs to the TGF-P superfamily and its role in vascular disease has not been characterized. The background and preliminary data suggest that these proteins may be important regulators of restenosis via their effects on vascular smooth muscle cell migration and proliferation. Based on his preliminary data, Dr. Guzman hypothesizes that BMP receptors may be ideal targets for gene-directed strategies to control intinial hyperplasia. The specific aims include: 1) Characterize the time course and cellular distribution of Bmp expression during pathologic arterial remodeling in mice. 2) Determine the role of shear stress in inducing endothelial BMP4 expression in-vitro. 3) Evaluate the effect of BMP type IA and IB receptor activation on injury-induced SMC proliferation and intinial accumulation in vivo. 4) Examine the effect of BMP type IA and IB receptor activation on SMC migration, invasion, and proliferation in vitro. In order to perform these specific aims, Dr. Guzman has outlined a research career development plan that includes a focused training period in the laboratory of Dr. Hogan along with course work in relevant areas. During this time he will learn to perform the techniques of in situ hybridization and double immunofluorescent staining. He will also learn fundamental techniques involved in the development of transgenic and knockout mouse strains. Dr. Guzman's long term goal is to make significant contributions to our understanding of pathologic arterial remodeling. It is expected that during this award period, Dr. Guzman will progress toward his goal of becoming an independent scientific investigator.