CoBRE TME-Determining MRI guided focused ultrasound parameters to safely open the blood-brain barrier in Alzheimer's disease

CoBRE TME - 确定 MRI 引导聚焦超声参数以安全打开阿尔茨海默氏病的血脑屏障

• 批准号: 10119416
• 负责人: Paul R Lockman
• 金额: $ 38万
• 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/10119416
• 关键词: Alzheimer' s Disease; Animal Cancer Model; Annual Reports; Appalachian Region; Area; Atmosphere; Award; Biology; Blood - brain barrier anatomy; 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; Focused Ultrasound; 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; Xenograft procedure; 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; 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.

项目摘要/摘要 该毛线应用中描述的努力将支持发展卓越中心 西弗吉尼亚大学健康科学中心（WVU HSC）将重点放在肿瘤研究上 微环境（TME），指定为TME毛病。持续重点的总体关键需求 在这一领域，部分原因是，癌症死亡率是重大健康差异 阿巴拉契亚地区，特别是在西弗吉尼亚州。可能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，从而影响生长，恶性，转移性 潜力和治疗反应。该建议旨在发展有前途的初级科学家的职业 并招募其他研究人员来研究将受益的新型治疗方法的生物学 来自对不同TME的机械理解。其中的五个高度翻译项目 应用的重点是不同肿瘤类型的微环境，包括在骨骼中引发的癌症 骨髓，头部和颈部，乳房和大脑。行政核心将管理整体预算并提供 在所有毛cre项目负责人的年度报告和提交壁外申请的协助。在 此外，此核心将提供对指导的监督，其中包括两个主要顾问 调查员和外部顾问，以及包括以前的索伯毕业生在内的网络和 核心资源总监。此外，支持团队还包括将提供的商业化专家 企业家和创新的培训。调查人员将通过扩大三个 由WVU现有核心建造的核心，完全利用了过去的思想支持。我们将扩大转基因 随着患者衍生的异种移植核的发展，以评估肿瘤生物学和药物的小鼠设施 直接从阿巴拉契亚患者服用的肿瘤的功效，与稳健的翻译性质一致 TME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 研究从TME分离的单细胞的基因组学。我们还将展示新成像 支持Microbeam辐照，微观核对，临床前MRI和实时微环境的技术 我们当前的动物成像设施中PO2和pH的成像。最后，我们将开发一个试点项目计划 在第二至五年中，将新的初级教师招募到TME Cobre。调查人员很好 纳入西弗吉尼亚大学癌症研究所的既定程序区域 每隔一个月，重点讨论TME的疗法和生物学的疗法。指导 氛围，核心设施以及这项努力核心的大量机构支持将为富人提供 培育研究人员独立性和成功科学领域的成功环境。