CELL CYCLE REGULATION IN INTESTINAL REGENERATION

王博士是哈佛医学院的一名外科讲师，他立志成为一名独立的研究员，致力于研究临床和基础科学之间的联系，为胃肠道疾病寻找新的治疗方法。这项提议的长期目标是开发治疗短肠综合征患者的新策略。慢性全肠外营养和肠道移植是目前这些患者唯一可用的选择；迫切需要新的方法。这些研究的基础假设是：1)特定的细胞周期调节机制调节大量小肠切除后适应过程中发生的肠道再生；2)对这些机制的了解可以被用来合理设计方法，最大限度地增强再生反应。三个具体目标将解决这些假设。前两个目的是利用1)体外还原模型和2)缺乏特定细胞周期调节因子的野生型和转基因小鼠来表征肠道再生中的细胞周期调节机制。第三个目标是设计和部署一种最大限度地刺激肠道再生的治疗性“鸡尾酒”。在该奖项的五年期间，王博士将获得研究胃肠道细胞周期调节的概念和方法方面的专业知识。来自外科调查和基础科学的协作指导将使这位年轻的外科医生获得成为独立调查员所需的技能。

Dr. Whang, an Instructor in Surgery at Harvard Medical School, aspires to become an independent investigator, working at the interfaces between clinical and basic sciences as he seeks new therapies for gastrointestinal disorders. The long-term goal of this proposal is to develop new strategies for treating patients suffering from the short bowel syndrome. Chronic total parenteral nutrition and intestinal transplantation are currently the only available options for these patients; new approaches are desperately needed. The hypotheses underlying these studies are 1) specific cell cycle regulatory mechanisms mediate intestinal regeneration that occurs during adaptation following massive small bowel resection and 2) an understanding of these mechanisms can be exploited to rationally design methods to maximally augment the regenerative response. Three specific aims will address these hypotheses. The first two aims are to characterize the cell cycle regulatory mechanisms in intestinal regeneration using 1) a reductionist in vitro model and 2) a wild-type and genetically-altered mice lacking specific cell cycle regulators. The third aim is to design and deploy a therapeutic "cocktail" that maximally stimulates intestinal regeneration. During he five-year period of this award, Dr. Whang will acquire expertise with the concepts and methods of studying cell cycle regulation in the gastrointestinal tract. Collaborative mentorship from both a surgical investigation and a basic scientific will allow this young surgeon to obtain the skills necessary to become an independent investigator.