Heterogeneity of wound macrophages

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): This Career Development Award will provide training and support to Dr. Jean M. Daley, Assistant Professor of Surgery (Research) at Brown University, as she becomes a progressively more independent researcher. The candidate is a general surgeon who 4 years ago embarked on a full time research career in wound biology. The career change was supported by the NIH "Supplement to Promote Reentry into Biomedical Research Careers", which provided training in skills necessary to conduct independent research. Dr. Daley's immediate career goal is the design and successful implementation of a multi-year research project invest- igating the role of macrophages in tissue repair. The candidate's long term goal is to apply her findings to human disease, and to identify targets for therapeutic intervention in impaired healing. Dr. Daley will work under the continued mentorship of Dr. Jorge Albina in the Department of Surgery at Brown, in a well- established group whose research focuses on the pathophysiology of injury, inflammation, and shock. The career development plan includes course work, conferences, and in-depth study of several content areas. Research plan: The management of wounds, burns, and injuries is an essential part of the practice of surgery; abnormal wound healing is a significant clinical problem. An understanding of normal repair provides a basis for investigations of and therapeutic intervention in abnormal repair. This proposal focuses on understanding of the role of macrophages in normal tissue repair, both in a sterile environment and in the presence of bacteria. Dr. Daley's data demonstrate two co-existant populations of wound macrophages: one shares characteristics of alternatively activated macrophages, the other shares characteristics of classically activated macrophages. The proposed experiments will test the hypothesis that a "correct" macrophage phenotype is essential for optimal wound healing, both in sterile injury and in the presence of bacteria. The proposal is structured in three specific aims, which will 1) characterize wound macrophage phenotypes, 2) identify determinants of wound macrophage phenotypes, and 3) determine the impact of macrophage phenotype on fibrosis in the wound. It is anticipated that findings in this animal model will provide a basis for investigation of wound macrophage phenotypes in human disease, and may identify targets for therapeutic interventions in abnormal healing.