Heterogeneity of wound macrophages

描述(由申请者提供)：该职业发展奖将为布朗大学外科(研究)助理教授Jean M.Daley博士提供培训和支持，因为她逐渐成为一名越来越独立的研究人员。候选人是一名普通外科医生，4年前开始了伤口生物学的全职研究生涯。这一职业转变得到了NIH《促进重返生物医学研究职业的补充资料》的支持，该补充文件提供了进行独立研究所需技能的培训。戴利博士近期的职业目标是设计并成功实施一项多年研究项目--研究巨噬细胞在组织修复中的作用。这位候选人的长期目标是将她的发现应用于人类疾病，并确定治疗康复受损的干预目标。戴利博士将在布朗大学外科Jorge Albina博士的持续指导下，在一个专注于损伤、炎症和休克的病理生理学研究的成熟小组中工作。职业发展计划包括课程工作、会议和对几个内容领域的深入研究。研究计划：创伤、烧伤和损伤的处理是外科实践中必不可少的一部分；伤口异常愈合是一个重大的临床问题。对正常修复的认识为异常修复的研究和治疗干预提供了基础。这项建议侧重于理解巨噬细胞在正常组织修复中的作用，无论是在无菌环境中还是在细菌存在的情况下。戴利博士的数据证明了伤口巨噬细胞的两种共存群体：一种具有交替激活的巨噬细胞的特征，另一种具有经典激活的巨噬细胞的特征。拟议的实验将检验这一假设，即无论是在无菌损伤还是在细菌存在的情况下，“正确的”巨噬细胞表型对于最佳的伤口愈合都是必不可少的。该提案有三个具体目标，将1)表征伤口巨噬细胞表型，2)确定伤口巨噬细胞表型的决定因素，3)确定巨噬细胞表型对伤口纤维化的影响。预计在该动物模型中的发现将为研究人类疾病的伤口巨噬细胞表型提供基础，并可能确定异常愈合的治疗干预的靶点。

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.