ROLE OF HEAT SHOCK PROTEINS IN CUTANEOUS BURN INJURY

热休克蛋白在皮肤烧伤中的作用

• 批准号: 6384928
• 负责人: DAVID M YOUNG
• 金额: $ 11.85万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/6384928
• 关键词: SDS polyacrylamide gel electrophoresis; burns; cell proliferation; cellular pathology; cytotoxicity; disease /disorder model; extracellular matrix proteins; gene expression; immunocytochemistry; laboratory rat; oxidation reduction reaction; protein structure function; protein tyrosine kinase; skin; skin transplantation; stress proteins; tissue /cell culture; western blottings; wound healing

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.

研究者是UCSF医学中心烧伤科主任和外科助理教授。 他有实验室空间，赞助商是资深的，资助的，科学家，并保证从他的主席的75%的保护研究时间，如果获得资金。 虽然候选人在烧伤研究方面有经验，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并加速伤口修复。 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）蛋白家族对升高的温度作出反应。 烧伤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。 他的具体目标包括1）确定响应于热损伤的热休克蛋白表达的特定模式和时间过程，并将特定热休克蛋白的水平与细胞存活、细胞增殖和新的细胞外基质的沉积相关联。他计划在原代皮肤细胞系、器官型筏皮肤培养物和大鼠皮肤中研究热损伤。 将使用蛋白质印迹分析和免疫化学染色测定热休克蛋白的水平。 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）和细胞外基质的产生（胶原蛋白合成）相关。 2)使用药物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。 他将使用在相同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。 结合他在烧伤治疗方面的临床专业知识和他提出的研究兴趣，他希望成为烧伤管理领域的独立研究者和领导者。 他将通过教学课程、每周研究研讨会、与赞助商的合作以及正在进行的临床工作来实现这一目标。