Tumor Microenvironment (TME) CoBRE

肿瘤微环境 (TME) CoBRE

• 批准号: 10487412
• 负责人: Paul R Lockman
• 金额: $ 222.99万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10487412
• 关键词: Animal Cancer Model; Annual Reports; Appalachian Region; Area; Atmosphere; Award; Biology; Blood Vessels; Bone Marrow; Brain; Breast; Budgets; Cell Survival; Cells; Centers of Research Excellence; Clinical Sciences; Collaborations; Core Facility; Development; Developmental Therapeutics Program; Disease; Entrepreneurship; Environment; Extracellular Matrix; Extramural Activities; Faculty; Faculty Recruitment; Feedback; Fibroblasts; Flow Cytometry; Funding; Genomics; Geography; Goals; Grant; Growth; Head and neck structure; Health Sciences; Health Services Accessibility; Image; Imaging technology; Immune; Immune response; Individual; Infrastructure; Institutes; Institution; Investments; Letters; Lymphocyte; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Mentors; Nature; Neoplasm Metastasis; Organ; Patients; Pattern; Pilot Projects; Positioning Attribute; Research; Research Infrastructure; Research Personnel; Resource Sharing; Resources; Scientist; Signal Transduction; Signaling Molecule; Structure; Time; Tissues; Training; Transgenic Mouse Facility; Translational Research; Tumor Biology; Universities; Vascular blood supply; West Virginia; Work; animal imaging; cancer imaging; career; career life balance; commercialization; directional cell; drug efficacy; health disparity; imaging facilities; improved; innovation; irradiation; member; microCT; mortality; neoplastic cell; new technology; novel strategies; novel therapeutic intervention; patient derived xenograft model; peer; pre-clinical; preclinical imaging; programs; recruit; single cell analysis; success; therapeutic target; training opportunity; translational scientist; treatment response; tumor; tumor microenvironment

PROJECT SUMMARY/ABSTRACT The efforts described in this CoBRE application will support development of a Center of Excellence within the West Virginia University Health Sciences Center (WVU HSC) that will focus on studies of the tumor microenvironment (TME), designated the TME CoBRE. The overarching critical need for continued emphasis in this area is driven, in part, by that fact that cancer mortality is a significant health disparity in the Appalachian region, specifically in West Virginia. Novel approaches that can impact disease must consider the interplay between a tumor and its host environment which influences growth, malignancy, metastatic potential, and therapeutic response. This proposal seeks to develop the careers of promising junior scientists and recruit additional investigators to study the biology of, and novel therapeutic approaches that will benefit from, a mechanistic understanding of the diverse TME. The five highly translational projects within this application focus on the microenvironment of different tumor types, including cancers initiating in the bone marrow, head and neck, breast, and brain. The administrative core will manage the overall budget and provide assistance in annual reporting and submission of extramural applications for all CoBRE Project Leaders. In addition, this core will provide oversight of mentoring, which includes two primary advisors for each investigator as well as an external advisor, and a network including previous CoBRE graduates and the Director of Core Resources. In addition, the support team include commercialization experts who will provide training in entrepreneurship and innovation. The investigators will be supported by the expansion of three cores built out of existing cores at WVU, fully leveraging past IDeA support. We will expand our transgenic mouse facility with the development of a patient-derived xenograft core to evaluate tumor biology and drug efficacy in tumors taken directly from Appalachian patients, aligned with the robust translational nature of the TME group. In addition, a new single cell analysis core will be established in the existing flow cytometry core to investigate the genomics of single cells isolated from the TME. We will also emplace new imaging technologies to support microbeam irradiation, microCT, pre-clinical MRI, and real time microenvironment imaging of pO2 and pH in our current animal imaging facility. Lastly, we will develop a pilot project program during years two through five to recruit new junior faculty to the TME CoBRE. The investigators are well integrated into established programmatic areas in the West Virginia University Cancer Institute that meet every other month for focused discussion on therapies for, and the biology of, the TME. The mentoring atmosphere, core facilities, and significant institutional support that are central to this effort will provide a rich environment to nurture investigator independence and success around the critical scientific area of TME.

项目概要/摘要 此 CoBRE 应用程序中描述的工作将支持在该领域内建立卓越中心 西弗吉尼亚大学健康科学中心 (WVU HSC) 将专注于肿瘤研究 微环境（TME），指定为 TME CoBRE。持续强调的首要迫切需要 这一领域的部分原因是癌症死亡率是一个显着的健康差距 阿巴拉契亚地区，特别是西弗吉尼亚州。必须考虑可能影响疾病的新方法 肿瘤与其宿主环境之间的相互作用，影响生长、恶性肿瘤、转移 潜力和治疗反应。该提案旨在发展有前途的初级科学家的职业生涯 并招募更多的研究人员来研究生物学和新的治疗方法，这将受益 从，对多样化 TME 的机械理解。其中五个高度转化的项目 应用重点关注不同肿瘤类型的微环境，包括始于骨的癌症 骨髓、头颈、乳房和大脑。行政核心将管理总体预算并提供 协助所有 CoBRE 项目负责人进行年度报告和提交校外申请。在 此外，该核心将提供指导监督，其中包括每个项目的两名主要顾问 研究员和外部顾问，以及包括以前的 CoBRE 毕业生和 核心资源总监。此外，支持团队包括商业化专家，他们将提供 创业创新培训。调查人员将得到三个扩展的支持 核心是在 WVU 现有核心的基础上构建的，充分利用了过去的 IDeA 支持。我们将扩大转基因 小鼠设施开发源自患者的异种移植核心以评估肿瘤生物学和药物 直接取自阿巴拉契亚患者的肿瘤的疗效，与该药物强大的转化性质相一致 TME集团.此外，将在现有流式细胞仪核心基础上建立新的单细胞分析核心 研究从 TME 中分离的单细胞的基因组学。我们还将放置新的成像 支持微束照射、microCT、临床前 MRI 和实时微环境的技术 在我们现有的动物成像设施中对 pO2 和 pH 进行成像。最后，我们将制定一个试点项目计划 在第二年到第五年期间，为 TME CoBRE 招募新的初级教师。调查人员状况良好 纳入西弗吉尼亚大学癌症研究所既定的规划领域，满足 每隔一个月就 TME 的疗法和生物学进行集中讨论。辅导 作为这项工作核心的氛围、核心设施和重要的机构支持将提供丰富的资源 培养研究者在 TME 关键科学领域的独立性和成功的环境。