CD8+ T Cell Response to Burn Injury

描述(由申请人提供)：候选人：首席研究员的目标是成为一名独立资助的外科科学家，将基础免疫学转化为解决严重烧伤和创伤中最具挑战性的问题的方案。首席研究员有很好的初步记录，完成了N1H-NRSA创伤培训奖学金，并发表了许多科学手稿。该提案旨在取得长期的科学成功，概述了一项具体的培训计划，其中包括教学工作、技术研讨会、直接实验室监督、伦理和应用基础科学研究的专业发展。环境：北卡罗来纳大学有着深厚的学术传统，致力于培养临床医生科学家。该学院拥有许多核心设施，包括莱恩伯格癌症中心和专门为支持临床科学家的发展而设计的分子生物学和生物技术项目。杰弗里·A·弗雷林格博士，微生物学和免疫学系主任，是这项建议的导师，他在科学上取得了长期的成功，并专门致力于首席研究员的科学发展。将向首席调查员提供成功完成本提案所需的所有实验室设备、资源、专业知识和办公空间。外科绝对致力于首席研究员的科学发展，他坚定地承诺将75%的时间花在这项提议上。研究：这项建议的目标是确定CD8+T细胞对烧伤的反应。CD8+T细胞越来越被认为是免疫反应的重要调节细胞，但对烧伤后的反应知之甚少。初步数据显示，虽然CTL对烧伤的同种异体反应受损，但激活的CD8+T细胞的表型表明促炎反应被夸大了。这一假说认为烧伤后CD8+T细胞的反应是多向性的，其机制是改变CD8+T细胞的活性。首席研究员将使用各种先进的细胞免疫学技术来确定烧伤后CD8+T细胞的表型和功能。此外，还将探讨CD8+T细胞活化的机制，特别是宿主环境和细胞因子环境如何影响CD8+T细胞对烧伤的反应。

DESCRIPTION (provided by applicant): Candidate: The goal of the principal investigator is to become an independently funded surgical scientist who translates basic immunology into solutions for the most challenging problems in severe burns and trauma. The principal investigator has a strong preliminary record, having completed a N1H-NRSA trauma training fellowship and published a number of scientific manuscripts. The proposal, designed for long-term scientific success, outlines a specific training plan that includes didactic work, technical workshops, direct laboratory supervision, ethics, and professional development in applied basic science research. Environment: UNC-CH has a strong academic tradition and a commitment to training clinician scientists. The school has a number of core facilities, including the Lineberger Cancer Center and the Program in Molecular Biology and Biotechnology specifically designed to support the development of clinician scientists. Dr. Jeffrey A. Frelinger, PhD, Chair, Department of Microbiology and Immunology, the mentor for this proposal, has a long track record of scientific success and is committed specifically to the scientific development of the principal investigator. All required laboratory equipment, resources, expertise, and office space necessary for successful completion of this proposal will be available to the principal investigator. The Department of Surgery is absolutely committed to the scientific development of the principal investigator and his firm commitment to spend 75% of his time on this proposal. Research: The goal of this proposal is to determine the CD8+ T cell response to burn injury. CD8+ T cells, increasingly recognized as an important regulator of the immune response, have a poorly understood response to burn injury. Preliminary data reveals that while the CTL alloresponse to burn injury is impaired, the phenotype of activated CD8+ T cells suggests an exaggerated proinflammatory response. The hypothesis of this proposal is that the CD8+ T cell response to burn injury is pleiotropic and the mechanism for this response is altered CD8+ T cell activation. The principal investigator will use a variety of advanced cellular immunologic techniques to determine the phenotype and function of CD8+ T cells after burn injury. In addition, the mechanisms of CD8+ T cell activation will be investigated, specifically how the host environment and the cytokine environment influence the CD8+ T cell response to burn injury.