Heterogeneity of wound macrophages

伤口巨噬细胞的异质性

• 批准号: 7793359
• 负责人: JEAN MARIE DALEY
• 金额: $ 12.15万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7793359
• 关键词: Animal Model; Apoptosis; Apoptotic; Area; Bacteria; Biology; Biomedical Research; Burn injury; Cells; Characteristics; Clinical; Data; Development; Development Plans; Environment; Fibroblasts; Fibrosis; Functional disorder; Goals; Healed; Heating; Heterogeneity; Impaired wound healing; In Situ; In Vitro; Induction of Apoptosis; Inflammation; Injury; Integrins; Investigation; K-Series Research Career Programs; Liver; Location; Macrophage Activation; Matrix Metalloproteinases; Mentorship; Modeling; Mus; Necrosis; Normal tissue morphology; Operative Surgical Procedures; Pattern; Phagocytosis; Phenotype; Population; Production; Proteins; Research; Research Personnel; Research Project Grants; Role; Shock; Staphylococcus aureus; Sterility; Structure; Surface Antigens; Surgeon; Testing; Therapeutic Intervention; Time; Tissues; Training; Training Support; United States National Institutes of Health; Universities; Variant; Work; Wound Healing; angiogenesis; base; career; career development; chemokine; cytokine; design; healing; human disease; in vivo; injury and repair; killings; macrophage; monocyte; neutrophil; pathogen; professor; programs; repaired; research study; skills; symposium; wound

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.

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员。该候选人是一名普通外科医生，4 年前开始从事伤口生物学的全职研究生涯。这一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个多年研究项目，研究巨噬细胞在组织修复中的作用。该候选人的长期目标是将她的发现应用于人类疾病，并确定针对愈合受损的治疗干预的目标。 Daley 博士将在布朗大学外科系的 Jorge Albina 博士的持续指导下工作，该团队的研究重点是损伤、炎症和休克的病理生理学。职业发展计划包括课程作业、会议以及对多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干预奠定了基础。该提案的重点是了解巨噬细胞在无菌环境和细菌存在下的正常组织修复中的作用。戴利博士的数据证明了两种共存的伤口巨噬细胞群：一种具有替代激活巨噬细胞的特征，另一种具有经典激活巨噬细胞的特征。拟议的实验将检验以下假设：“正确的”巨噬细胞表型对于最佳伤口愈合至关重要，无论是在无菌损伤还是在细菌存在的情况下。该提案分为三个具体目标，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，3) 确定巨噬细胞表型对伤口纤维化的影响。预计该动物模型的发现将为人类疾病中伤口巨噬细胞表型的研究提供基础，并可能确定异常愈合治疗干预的目标。