Thrombin Signaling in Hemostasis and Thrombosis

描述(由申请人提供)： 该提案将概述一项为期5年的研究和培训计划，旨在为首席研究员配备必要的工具，使其成为一名学术内科科学家。他已经完成了严格的内科和心脏病学临床培训计划，并在分子和细胞心脏病学方面接受了广泛的培训。他现在正准备从事学术医学的职业生涯，这个项目将提供一个独特的机会，帮助他发展成为一名独立的医生-研究员。 赞助商肖恩·考夫林博士将直接监督该项目和首席研究员的职业发展。考夫林博士是止血和血栓形成领域最重要和备受尊敬的领导者之一，他的实验室的工作帮助定义了蛋白酶受体生物学领域。他是加州大学旧金山分校CVRI的主任，他自己也是一名训练有素的心脏病专家，指导过许多年轻内科科学家的发展。该计划将寻求一个咨询委员会的帮助，该委员会包括三名有成就的学术内科科学家--他们都是部门主席。 这项研究计划是根据首席研究人员在赞助商实验室担任研究员时开始的一系列工作自然设计的。这包括观察到小鼠血小板中的凝血酶信号通过PAR4发生。小鼠PAR4编码基因的敲除导致体内异常止血和血栓形成受损的表型。该提案描述了一项计划，1)使用骨髓移植来研究血小板相对于内皮细胞中凝血酶信号的特定干扰是否会损害体内的血栓形成或止血，以及2)确定凝血酶信号的干扰如何影响血栓形成或止血。 加州大学旧金山分校的CVRI和医学系是开展计划中所述培训和工作的理想场所。在生物医学科学的几乎每一个领域都有专业知识，在临床护理方面也有出色的表现。气氛是合作共事的，有充足的学习和发展机会。最后，该机构对候选人的职业发展有着深切的承诺，首席研究员有很高的潜力成功实现他的目标，建立一个杰出的独立项目和学术生涯。

DESCRIPTION (provided by applicant): The proposal will outline a 5-year research and training plan designed to equip the principal investigator with the tools necessary for his development as an academic physician-scientist. He has completed a rigorous clinical training program in internal medicine and cardiology and has had extensive training in molecular and cellular cardiology. He is now poised for a career in academic medicine, and this program will offer a unique opportunity to foster his development into an independent physician-investigator. The sponsor, Dr. Shaun Coughlin, will directly oversee the project and the career development of the principal investigator. Dr. Coughlin is one of the foremost and highly respected leaders in the field of hemostasis and thrombosis, and work from his laboratory has helped to define the field of protease receptor biology. He is the director of the CVRI at UCSF, and is himself a trained cardiologist who has mentored the development of many young physician scientists. The program will enlist the help of an advisory committee that includes three accomplished academic physician scientists-all division chairmen. The research plan is designed to follow naturally from a body of work started by the principal investigator while a fellow in the sponsor's laboratory. This includes the observation that thrombin signaling in mouse platelets occurs through PAR4. Knockout of the gene encoding mouse PAR4 resulted in a phenotype of abnormal hemostasis and impaired thrombosis in vivo. The proposal describes a plan to 1) use bone marrow transplantation to ask whether specific disruption of thrombin signaling in platelets versus endothelial cells can impair thrombosis or hemostasis in vivo, and 2) to define how disruptions in thrombin signaling can affect thrombosis or hemostasis. The CVRI and the Department of Medicine at UCSF are the ideal settings to carry out the training and the work described in the proposal. There is expertise in nearly every area of biomedical science and excellence in clinical care. The atmosphere is collegial and collaborative, and there are ample opportunities for learning and development. Finally, there is a deep commitment from the institution to the career development of the candidate and a high potential for the principal investigator to succeed in his goals to establish a distinguished independent program and academic career.