ROLE OF HEAT SHOCK PROTEINS IN CUTANEOUS BURN INJURY

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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.