Tumor Microenvironment-TME CoBRE

肿瘤微环境-TME CoBRE

• 批准号: 10709266
• 负责人: Paul R Lockman
• 金额: $ 222.21万
• 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 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10709266
• 关键词: Annual Reports; Apoptosis; Appalachian Region; Area; Atmosphere; Award; Biology; Biometry; Bone Marrow; Bone Marrow Neoplasms; Brain; Breast; Breast Cancer Detection; Budgets; Cell Survival; Cells; Centers of Research Excellence; Cessation of life; Clinical Informatics; Clinical Research; Collaborations; Communication; Core Facility; Cues; Data; Development; Disease; Education; Education and Outreach; Environment; Enzymes; Extramural Activities; Faculty; Faculty Recruitment; Feedback; Flow Cytometry; Foundations; Funding; Gastritis; Genomics; Goals; Grant; Growth; Health Sciences; Helicobacter Infections; Image; Immune system; Immunotherapy; Individual; Infrastructure; Institution; Invaded; Investigation; Investments; Joints; Laboratories; Leucine Zippers; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Mentors; Multi-Drug Resistance; Multiple Myeloma; Myeloid-derived suppressor cells; National Institute of General Medical Sciences; Neoplasm Metastasis; Organ; Paper; Personal Satisfaction; Phase; Physical environment; Physiological; Pilot Projects; Positioning Attribute; Productivity; Proliferating; Publications; Publishing; Reactive Oxygen Species; Research; Research Infrastructure; Research Personnel; Research Support; Resources; Role; Schools; Scientist; Signal Transduction; Stomach; Students; System; Teacher Professional Development; Techniques; Technology; Time; Tissues; Training; Translational Research; Tumor Suppression; Universities; West Virginia; Workforce Development; cancer cell; cancer initiation; career; career life balance; clinical translation; course development; defined contribution; directional cell; gastric carcinogenesis; health disparity; imaging agent; improved; irradiation; meetings; melanoma; member; microCT; mortality; neoplastic cell; neutrophil; novel therapeutic intervention; outreach program; pancreatic neoplasm; peer; pre-clinical; programs; recruit; response; single cell analysis; success; training opportunity; transcription factor; tumor; tumor growth; tumor microenvironment; tumor progression; tumor-immune system interactions; undergraduate student

PROJECT SUMMARY/ABSTRACT The efforts described in this second phase CoBRE application will support the Center of Excellence within the West Virginia University Health Sciences Center (WVU HSC) that focuses 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. We are building on a successful Phase I, where we had two graduates with R01s, a major national foundation grant, a NSF grant, an R21 and our cores were awarded two S10 awards. In total we had 11 Project Leader (PL) awards as PI, and 8 as a Co-I. The Center has grown to over 20 faculty, including a number of faculty who are potential PLs, with their teams publishing over 140 papers since initiation of Phase I. Laboratories supported, in part, by the Phase I TME CoBRE, have engaged in the training of ~60 students further amplifying the impact of the NIGMS investment on workforce development in parallel to CoBRE PL success. Herein, we provide details for the strategy to continue to develop 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 in Phase II focus on the microenvironment of different tumor types, including cancers initiating in the bone marrow, gastric system, breast, and brain. The administrative core will manage the overall budget and provide assistance in annual reporting and submission of extramural applications of 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 of previous CoBRE graduates and the Director of Core Resources. The investigators will be supported by two research cores that leverage past and current CoBRE and IDeA support. Single cell analysis capability in the existing flow cytometry core will aid to it investigations into genomics of single cells. The Imaging Core will support PLs with cutting edge technologies including microbeam irradiation, microCT, pre-clinical MRI, and real time microenvironment imaging of pO2 and pH. Lastly, we will continue to administer a pilot project program to recruit new junior faculty to the TME CoBRE, as we saw five of six pilot grant awardees eventually become PLs, and we currently have a robust number of junior investigators (#5) may become PLs as well. 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 that leverage, and the biology of, the TME. The mentoring atmosphere, core facilities, and significant institutional support that are central to this effort will continue to provide a rich environment to nurture investigator independence and success around the critical scientific area of TME.

项目总结/摘要 第二阶段CoBRE应用程序中描述的工作将支持卓越中心， 西弗吉尼亚大学健康科学中心（WVU HSC），专注于肿瘤的研究 微环境（TME），指定为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。我们正在建立一个成功的第一阶段，我们有两个 R 01毕业生，一个主要的国家基金会赠款，NSF赠款，R21和我们的核心被授予 两个S10奖项作为PI，我们总共获得了11个项目负责人（PL）奖，8个Co-I奖。该中心已成长 超过20名教师，包括一些潜在的PL教师，他们的团队发表了140多篇文章。 自第一阶段启动以来的论文。部分由第一阶段TME CoBRE支持的实验室已经参与了 培训了约60名学生，进一步扩大了NIGMS投资对劳动力的影响 与CoBRE PL成功并行的开发。在此，我们提供了该战略的细节， 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， 新的治疗方法，将受益于不同的TME的机械理解。的 第二阶段的五个高度转化的项目专注于不同肿瘤类型的微环境，包括 在骨髓、胃系统、乳腺和脑中开始的癌症。行政核心将管理 总体预算，并在年度报告和提交校外申请方面提供援助， 所有Cobre项目负责人。此外，这一核心还将监督辅导工作，其中包括两个 每个研究者的主要顾问以及外部顾问，以及以前的CoBRE网络 毕业生和核心资源主任。研究人员将得到两个研究核心的支持 利用过去和当前的CoBRE和IDEA支持。现有流程中的单细胞分析能力 流式细胞术核心将有助于单细胞基因组学的研究。成像核心将支持PL 尖端技术，包括微束辐射、microCT、临床前MRI和真实的时间 最后，我们将继续管理一个试点项目计划， 招募新的初级教师到TME CobRE，因为我们看到六个试点补助金获得者中有五个最终成为 PL，我们目前有大量的初级调查员（#5）也可能成为PL。的 研究人员很好地融入了西弗吉尼亚大学癌症研究所的既定计划领域， 研究所每隔一个月举行一次会议，集中讨论利用的疗法，以及生物学， 的TME。指导氛围、核心设施和重要的机构支持是 这一努力将继续提供一个丰富的环境，以培养调查人员的独立性和成功 围绕TME的关键科学领域。

项目成果

Pitavastatin Is Anti-Leukemic in a Bone Marrow Microenvironment Model of B-Lineage Acute Lymphoblastic Leukemia.

Pitavastatin是B-Linege急性淋巴细胞白血病的骨髓微环境模型中的抗白血病。

• DOI: 10.3390/cancers14112681
• 发表时间: 2022-05-28
• 期刊: CANCERS
• 影响因子: 5.2
• 作者: Piktel, Debbie;Nair, Rajesh R.;Rellick, Stephanie L.;Geldenhuys, Werner J.;Martin, Karen H.;Craig, Michael D.;Gibson, Laura F.
• 通讯作者: Gibson, Laura F.

Mesenchymal COX2-PG secretome engages NR4A-WNT signalling axis in haematopoietic progenitors to suppress anti-leukaemia immunity.

间充质Cox2-PG分粒子与造血祖细胞中的NR4A-WNT信号轴接合，以抑制抗leukaemia的免疫力。

• DOI: 10.1111/bjh.15548
• 发表时间: 2018-11
• 期刊: British journal of haematology
• 影响因子: 6.5
• 作者: Wu L;Amarachintha S;Xu J;Oley F Jr;Du W
• 通讯作者: Du W

Interphotoreceptor matrix proteoglycans IMPG1 and IMPG2 proteolyze in the SEA domain and reveal localization mutual dependency.

• DOI: 10.1038/s41598-022-19910-1
• 发表时间: 2022-09-15
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Mitchell, Benjamin;Coulter, Chloe;Geldenhuys, Werner J.;Rhodes, Scott;Salido, Ezequiel M.
• 通讯作者: Salido, Ezequiel M.

Symbiosis preservation: Putative regulation of fatty acyl-CoA reductase by miR-31a within the symbiont harboring bacteriome through tsetse evolution.

• DOI: 10.3389/fmicb.2023.1151319
• 发表时间: 2023
• 期刊: Frontiers in microbiology
• 影响因子: 5.2

Interleukin-27 impairs BCG antigen clearance and T cell stimulatory potential by neonatal dendritic cells.

• DOI: 10.1016/j.crmicr.2022.100176
• 发表时间: 2023
• 期刊: CURRENT RESEARCH IN MICROBIAL SCIENCES
• 作者: Bradford, Shelby D.;Witt, Michelle R.;Povroznik, Jessica M.;Robinson, Cory M.
• 通讯作者: Robinson, Cory M.