Tumor Microenvironment (TME) CoBRE

项目概要/摘要 本CoBRE应用程序中描述的工作将支持在 西弗吉尼亚大学健康科学中心（WVU HSC）将专注于肿瘤的研究 微环境（TME），称为TME CoBRE。至关重要的是，必须继续强调 在这一领域，部分原因是癌症死亡率是世界上 阿巴拉契亚地区，特别是在西弗吉尼亚州。可以影响疾病的新方法必须考虑 肿瘤与其宿主环境之间的相互作用，其影响生长、恶性、转移 潜力和治疗反应。这项建议旨在发展有前途的年轻科学家的职业生涯 并招募更多的研究人员来研究生物学和新的治疗方法， 从对不同的TME的机械理解。其中五个高度翻译的项目 应用集中于不同肿瘤类型的微环境，包括在骨骼中开始的癌症 骨髓、头颈、乳房和大脑。行政核心将管理总体预算， 协助所有CoBRE项目负责人提交年度报告和校外申请。在 此外，该核心还将提供指导监督，其中包括为每个核心配备两名主要顾问 调查员以及外部顾问，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 创业和创新培训。调查人员将得到扩大的三个 在WVU的现有核心基础上构建核心，充分利用过去的IDEA支持。我们将扩大我们的转基因 小鼠设施，开发患者来源的异种移植核心，以评价肿瘤生物学和药物 在直接取自阿巴拉契亚患者的肿瘤中的疗效，与 TME集团。此外，还将在现有的流式细胞仪核心中建立新的单细胞分析核心 研究从TME分离的单细胞的基因组学。我们还将安置新的成像设备， 支持微束照射、microCT、临床前MRI和真实的时间微环境的技术 pO 2和pH成像在我们目前的动物成像设施。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。调查人员很好 整合到西弗吉尼亚大学癌症研究所的既定方案领域， 每隔一个月，集中讨论TME的治疗方法和生物学。辅导 环境、核心设施和重要的机构支持是这一努力的核心，将提供丰富的 环境，以培养研究者的独立性和成功周围的关键科学领域的TME。

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.