Heterogeneity of wound macrophages

描述（由申请人提供）：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，帮助她逐渐成为一名更加独立的研究人员。候选人是一名普通外科医生，四年前开始了伤口生物学的全职研究生涯。职业转变得到了美国国立卫生研究院“促进重新进入生物医学研究职业的补充”的支持，该补充提供了进行独立研究所需的技能培训。Daley博士的近期职业目标是设计并成功实施一项多年的研究项目，研究巨噬细胞在组织修复中的作用。候选人的长期目标是将她的发现应用于人类疾病，并确定治疗干预受损愈合的目标。Daley博士将继续在布朗大学外科部门Jorge Albina博士的指导下工作，该部门的研究重点是损伤、炎症和休克的病理生理学。职业发展计划包括课程作业、会议和对几个内容领域的深入研究。研究计划：伤口、烧伤和损伤的处理是外科实践的重要组成部分；伤口愈合异常是一个重要的临床问题。对正常修复的理解为异常修复的研究和治疗提供了基础。这一建议的重点是理解巨噬细胞在正常组织修复中的作用，无论是在无菌环境还是在细菌存在的情况下。Daley博士的数据证明了两种共存的伤口巨噬细胞群体：一种具有选择性活化巨噬细胞的特征，另一种具有经典活化巨噬细胞的特征。提出的实验将验证“正确的”巨噬细胞表型对于无菌损伤和细菌存在的最佳伤口愈合至关重要的假设。该提案有三个具体目标，即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，以及3)确定巨噬细胞表型对伤口纤维化的影响。预计该动物模型的研究结果将为研究人类疾病中的伤口巨噬细胞表型提供基础，并可能为异常愈合的治疗干预提供靶点。

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.