CELL CYCLE REGULATION IN INTESTINAL REGENERATION

肠道再生中的细胞周期调节

• 批准号: 6342412
• 负责人: EDWARD E WHANG
• 金额: $ 12.85万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-15 至 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6342412
• 关键词: cell growth regulation; cyclin dependent kinase; gastrointestinal agents; gastrointestinal surgery; intestines; laboratory mouse; postoperative state; regeneration; short bowel syndrome; tissue /cell culture

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.

黄博士是哈佛医学院的外科讲师，他渴望成为一名独立的研究人员，在临床和基础科学之间的接口工作，因为他寻求胃肠道疾病的新疗法。该提案的长期目标是开发治疗短肠综合征患者的新策略。慢性全胃肠外营养和肠移植是目前这些患者唯一可用的选择;迫切需要新的方法。这些研究的基本假设是：1）特定的细胞周期调节机制介导大面积小肠切除后适应过程中发生的肠再生; 2）对这些机制的理解可以用于合理设计方法，以最大限度地增强再生反应。三个具体目标将解决这些假设。前两个目的是表征肠再生中的细胞周期调节机制，使用1）还原体外模型和2）缺乏特异性细胞周期调节剂的野生型和遗传改变的小鼠。第三个目标是设计和部署一种治疗“鸡尾酒”，最大限度地刺激肠道再生。在该奖项的五年期间，黄博士将获得研究胃肠道细胞周期调节的概念和方法的专业知识。来自外科调查和基础科学的合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。