COBRE CORE B: DMS: MOLECULAR BIOLOGY CORE/IMMUNE MONITORING LABORATORY

COBRE CORE B：DMS：分子生物学核心/免疫监测实验室

• 批准号: 7170493
• 负责人: Joyce A De Leo
• 金额: $ 16.27万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7170493
• 关键词: immunoregulation; inflammation; neoplasm /cancer immunology

DESCRIPTION (provided by applicant): The ultimate goals of this COBRE application are to increase the numbers of investigators in New Hampshire who are competitive m securing NIH extramural funding, and to establish an Immunology and Inflammation Center that will be nationally recognized and free standing in five years. Based on a highly interactive core of existing collaborative and multidisciplinary faculty at Dartmouth Medical School (DMS) and Dartmouth Hitchcock Medical Center (DHMC), along with several key faculty at the University of New Hampshire (UNH) at Durham, the COBRE mechanism will provide the resources to grow the Program in terms of both faculty development and the infrastructure necessary to attain functional center status. Faculty growth will be facilitated by COBRE funding in four ways: 1) recruitment of five tenure-track faculty: two at the University of New Hampshire, and three at DMS/DHMC; 2) mentored development of five promising junior investigators already at Dartmouth, as the Project Leaders of the five Research . Projects; 3) further linkage between DMS/DHMC and the UNH through Dr. Bruce Reinhold (Assistant Professor at UNH), a key co-Investigator who will provide mass spectrometry expertise not available at DMS and DHMC; and also Drs. Vernon Reinhold (Project 3) and Thomas Pistole (Project 2) of UNH; and 4) synergistic scientific collaboration through the five research projects and associated cores. Under the leadership of P.I. Dr. William R. Green, the current Director of the DMS/DHMC Immunology Program, together with substantive institutional commitment by both DMS/DHMC and UNH, there is confidence that the strong existing base of investigators can be expanded and matured by the COBRE mechanism to establish a Center, comprised of faculty who will be substantially more competitive in obtaining extramural NIH funding, and thereby enhance the research grant portfolio of the State. The five individual research projects exhibit the multidisciplinary breadth characteristic of a center but also are intertwined by the common theme of modulation of immunity in various disease states, both at the level of non-specific inflammatory processes as well as with respect to specific adaptive immunity. Project 1 examines the central role of the cytokine tumor necrosis factor alpha (TNF-a) in inflammatory processes and autoimmune disease, and the regulation of TNF-a production in T lymphocytes at the level of post-transcriptional control of mRNA stability. Project 2 studies the roles that macrophage activation and cytokines, in particular TGF-B1, play in the inflammatory processes involved in septic shock induced by lipopolysaccharide from Gram-negative bacteria, and in the liver inflammation observed in TGF-B1- deficient mice. In Project 3 biochemical and biophysical techniques are employed to define the processing pathways of novel lipophilic antigens of M. tuberculosis for presentation by CD1, a monomorphic class 1B presenting molecule, as the basis for vaccine development. Project 4 utilizes the approach of CD64 targeting of antigen to professional antigen presenting cells (APC), overlayed with various strategies of APC activation, to amplify T cell responses in human systems to prostate cancer related antigens. In Project 5 augmentation of antigen loading and activation of dendritic cell (DC) APC form the foundation for both preclinical studies and clinical trials to define DC-based vaccines for colorectal cancer. Together these projects will contribute to defining creative new ways by which immune responses can be modulated either positively to combat tumors and bacterial infections, or in a down-regulatory manner to lessen unwanted inflammation and autoimmunity.

描述（由申请人提供）：本 COBRE 的最终目标 申请的目的是增加新罕布什尔州调查人员的数量 在获得 NIH 外部资金方面具有竞争力，并建立一个 免疫学和炎症中心将获得国家认可且免费 五年后站立。基于现有的高度交互核心 达特茅斯医学院 (DMS) 的协作和多学科教师 和达特茅斯希区柯克医疗中心 (DHMC)，以及几位主要教员 在位于达勒姆的新罕布什尔大学 (UNH)，COBRE 机制将 提供资源以促进该计划在教师发展方面的发展 以及获得功能中心地位所需的基础设施。学院 COBRE 资金将通过四种方式促进增长：1) 招募 五名终身教授：两名在新罕布什尔大学，三名 在 DMS/DHMC； 2）指导培养五名有前途的初级研究员 已经在达特茅斯担任五个研究的项目负责人。项目； 3) 通过 Bruce Reinhold 博士进一步加强 DMS/DHMC 和 UNH 之间的联系 （新罕布什尔大学助理教授），一位关键的联合研究员，将提供质量 DMS 和 DHMC 不具备光谱测定专业知识；还有博士。弗农 UNH 的 Reinhold（项目 3）和 Thomas Pistole（项目 2）； 4) 协同作用 通过五个研究项目和相关的科学合作 核心。在 P.I. 的领导下威廉·R·格林博士，现任 DMS/DHMC 免疫学项目主任，以及实质性人员 DMS/DHMC 和 UNH 的机构承诺，有信心 现有强大的调查人员基础可以通过以下方式扩大和成熟： COBRE 机制建立一个中心，由将 在获得 NIH 外部资助方面更具竞争力，并且 从而增强国家的研究补助金组合。 五个单独的研究项目展现了多学科的广度 中心的特征，但也与共同的主题交织在一起 在各种疾病状态下调节免疫，无论是在非特异性水平 炎症过程以及特定的适应性 免疫。项目 1 检查细胞因子肿瘤坏死的核心作用 炎症过程和自身免疫性疾病中的α因子（TNF-a），以及 在转录后水平调节 T 淋巴细胞中 TNF-a 的产生 mRNA稳定性的控制。项目 2 研究的角色 巨噬细胞活化和细胞因子，特别是 TGF-B1，在 脂多糖诱导的感染性休克涉及的炎症过程 来自革兰氏阴性菌，并在 TGF-B1- 中观察到的肝脏炎症中 缺乏的老鼠。在项目 3 中，生物化学和生物物理技术是 用于定义 M. 新型亲脂性抗原的加工途径。 结核病由 CD1 呈现，单态 1B 类呈现 分子，作为疫苗开发的基础。项目 4 利用 CD64将抗原靶向专职抗原呈递细胞的方法 (APC)，叠加各种 APC 激活策略，以扩增 T 细胞 人体系统对前列腺癌相关抗原的反应。在项目5中 增强抗原负载并激活树突状细胞 (DC) APC 形式 为定义基于 DC 的临床前研究和临床试验奠定了基础 结直肠癌疫苗。这些项目将共同做出贡献 定义调节免疫反应的创造性新方法 要么积极对抗肿瘤和细菌感染，要么下调 减少不必要的炎症和自身免疫的方式。