Tumor Microenvironment (TME) CoBRE

项目摘要/摘要 此Cobre申请中描述的努力将支持在 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)，命名为TME Cobre。继续强调最重要的迫切需要 在这一领域，部分原因是癌症死亡率在全球范围内是一个显著的健康差距 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，影响生长、恶性肿瘤和转移 潜力和治疗反应。这项提议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将受益的生物学和新的治疗方法 来自于对多样化的TME的机械性理解。其中五个极具翻译性的项目 应用重点是不同肿瘤类型的微环境，包括始发于骨的癌症 骨髓、头部和颈部、胸部和大脑。行政核心将管理总体预算并提供 协助所有科布雷项目负责人的年度报告和提交校外申请。在……里面 此外，这个核心将提供对指导的监督，每个指导包括两名主要顾问 调查员以及一名外部顾问，以及包括科布雷以前的毕业生和 核心资源总监。此外，支持团队还包括商业化专家，他们将提供 开展创业创新培训。调查人员将得到三名扩编人员的支持 在西弗吉尼亚州立大学现有核心的基础上构建的核心，充分利用了过去的创意支持。我们将扩大我们的转基因产品 开发患者来源的异种移植核心以评估肿瘤生物学和药物的小鼠设施 对直接取自阿巴拉契亚地区患者的肿瘤的疗效，与该基因强大的翻译性质一致 这是一组。此外，将在现有的流式细胞仪核心中建立一个新的单细胞分析核心 目的：对分离自TME的单细胞进行基因组学研究。我们还将部署新的成像设备 支持微束照射、微CT、临床前核磁共振和实时微环境的技术 在我们目前的动物成像设备中对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招聘新的初级教员。调查人员都很好 整合到西弗吉尼亚大学癌症研究所既定的方案领域，满足 每隔一个月集中讨论TME的治疗方法和生物学问题。指导工作 对这一努力至关重要的氛围、核心设施和重要的制度支持将提供丰富的 围绕TME关键科学领域培养研究人员独立性和成功的环境。

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.