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.

项目摘要/摘要 在第二阶段的索布雷应用程序中所描述的努力将支持卓越中心 西弗吉尼亚大学健康科学中心（WVU HSC），该中心重点介绍肿瘤的研究 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。我们正在成功的第一阶段，我们有两个 拥有R01的毕业生，主要的国家基金会赠款，NSF赠款，R21和我们的核心获得了授予 两个S10奖项。我们总共获得了11项项目负责人（PL）奖项，为PI，8项作为Co-I。中心已经成长 超过20多名教师，包括许多潜在的教师，他们的团队出版了140多个 自第一阶段开始以来的论文，部分由I阶段ITME COBRE支持 在培训约60名学生中 与Cobre pl成功的发展。在此，我们为策略提供了详细信息 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和 对各种TME的机械理解将受益的新型治疗方法。这 第二阶段中的五个高度转化项目的重点是不同肿瘤类型的微环境，包括 在骨髓，胃系统，乳房和大脑中发起的癌症。行政核心将管理 总体预算，并在年度报告和提交壁外申请的协助 所有毛茸茸的项目负责人。此外，该核心将提供对指导的监督，其中包括两个 每个调查员和外部顾问的主要顾问，以及先前的cobre网络 毕业生和核心资源总监。调查人员将得到两个研究核心的支持 这种利用了过去和当前的毛绒和想法支持。现有流中的单细胞分析能力 细胞仪核心将有助于IT研究单细胞的基因组学。成像核心将支持PLS 使用尖端技术，包括微束辐射，微观仪，临床前MRI和实时 PO2和PH的微环境成像。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，因为我们看到六名试点赠款获奖者中有五名最终成为 PLS，我们目前有大量的初级调查人员（＃5）也可能会成为PLS。这 调查人员已很好地融入了西弗吉尼亚大学癌症的既定程序区域 每隔一个月开会一次的研究所，重点讨论杠杆的疗法以及生物学的生物学 TME。指导气氛，核心设施和大量机构支持是 这项努力将继续提供丰富的环境来培养研究者的独立性和成功 在TME的关键科学领域附近。

项目成果

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

• 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.

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.

E-Cigarette Use: Device Market, Study Design, and Emerging Evidence of Biological Consequences.

• DOI: 10.3390/ijms222212452
• 发表时间: 2021-11-18
• 期刊: International journal of molecular sciences
• 影响因子: 5.6
• 作者: Snoderly HT;Nurkiewicz TR;Bowdridge EC;Bennewitz MF
• 通讯作者: Bennewitz MF

Genetically Defined Subtypes of Somatostatin-Containing Cortical Interneurons.

含有生长抑素的皮质中间神经元的基因定义亚型。

• DOI: 10.1101/2023.02.02.526850
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Hostetler,RachelE;Hu,Hang;Agmon,Ariel
• 通讯作者: Agmon,Ariel

Adaptation of the group A Streptococcus adhesin Scl1 to bind fibronectin type III repeats within wound-associated extracellular matrix: implications for cancer therapy.

A 组链球菌粘附素 Scl1 适应伤口相关细胞外基质内的纤连蛋白 III 型重复序列：对癌症治疗的影响。

• DOI: 10.1111/mmi.14317
• 发表时间: 2019
• 期刊: Molecular microbiology
• 影响因子: 3.6
• 作者: McNitt,DudleyH;Choi,SooJeon;Allen,JessicaL;Hames,RiverA;Weed,ScottA;VanDeWater,Livingston;Berisio,Rita;Lukomski,Slawomir
• 通讯作者: Lukomski,Slawomir