ROLE OF HEAT SHOCK PROTEINS IN CUTANEOUS BURN INJURY

热休克蛋白在皮肤烧伤中的作用

基本信息

批准号：
6658981
负责人：
DAVID M YOUNG
金额：
$ 12.08万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-09-30 至 2004-09-29
项目状态：
已结题

项目摘要

The investigator is Director of the Burn Unit and Assistant Professor of Surgery at UCSF Medical Center. He has laboratory space, sponsors who are senior, funded, scientists, and assurances from his Chairman of 75 percent protected research time if funding is obtained. Although the candidate has experience in burn research, he requires extra training to develop expertise in molecular biologic methods. A primary goal of burn therapy is limiting the extent of tissue injury and accelerating wound repair. Understanding the molecular signals of injury and repair may lead to new methods to treat burn patients. Cells respond to elevated temperatures by expression of a family of heat shock (or stress) proteins. Burn is a form of heat shock and these proteins have important functions in injury and repair processes. His specific aims include 1) Determine the specific pattern and time course of heat shock protein expression in response to thermal injury and correlate levels of specific heat shock proteins with cell survival, cell proliferation, and the deposition of new extracellular matrix. He plans to study thermal injury in primary skin cell lines, organotypic raft skin cultures, and rat skin. Levels of heat shock proteins will be determined using western blot analysis and immunochemical staining. These levels will be correlated to cell survival (membrane integrity and metabolic activity), proliferation (mitotic index) and production of extracellular matrix (collagen synthesis). 2) Modulate heat shock protein levels in the wound using drugs to limit cell injury and accelerate wound repair. He will use drugs that modulate levels of heat shock proteins in the same model systems to determine whether alterations of heat shock protein levels can influence cell survival, affect proliferation, or alter production of extracellular matrix in an effort to limit cell injury and enhance wound repair. Combining his clinical expertise in burn treatment and his proposed research interests, he hopes to establish himself as an independent investigator and a leader in the field of burn management. He will achieve this goal through didactic courses, weekly research seminars, collaboration with his sponsors, and ongoing clinical work.

研究人员是UCSF医疗中心烧伤部门的主任和外科助理教授。他拥有实验室空间，由高级，资助，科学家的赞助商，以及他的75％的主席，如果获得资金，则受到75％的保护时间的保证。尽管候选人在烧伤研究方面具有经验，但他需要额外的培训来发展分子生物学方法的专业知识。烧伤治疗的主要目标是限制组织损伤的程度和加速伤口修复。了解损伤和修复的分子信号可能会导致治疗烧伤患者的新方法。细胞通过表达热休克（或应激）蛋白家族来应对温度升高。燃烧是热休克的一种形式，这些蛋白质在损伤和修复过程中具有重要功能。他的具体目的包括1）确定热激蛋白表达的特定模式和时间过程，响应热损伤，并将特定热激蛋白的水平与细胞存活，细胞增殖以及新细胞外基质的沉积相关。他计划研究原代皮肤细胞系，器官筏皮肤培养物和大鼠皮肤的热损伤。热休克蛋白的水平将使用蛋白质印迹分析和免疫化学染色确定。这些水平将与细胞存活（膜完整性和代谢活性），增殖（有丝分裂指数）和细胞外基质（胶原蛋白合成）相关。 2）使用药物来调节伤口中的热休克蛋白水平，以限制细胞损伤并加速伤口修复。他将使用在同一模型系统中调节热休克蛋白水平的药物来确定热休克蛋白水平的改变是否会影响细胞存活，影响增殖或改变细胞外基质的产生，以限制细胞损伤并增强伤口修复。他希望将自己的临床专业知识与他提出的研究兴趣相结合，希望自己成为独立研究者和烧伤管理领域的领导者。他将通过教学课程，每周的研究研讨会，与赞助商合作以及持续的临床工作来实现这一目标。