Cancer Biology Research Program

癌症生物学研究计划

基本信息

批准号：
10628431
负责人：
Azeddine Atfi
金额：
$ 3.32万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-12-01 至 2028-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10628431
关键词：
Ablation Accounting Activins Address Affect Apoptosis Articulation Autophagocytosis Award Awareness Basic Science Biological Cancer Biology Cancer Burden Cancer Center Cancer Center Support Grant Cancer Control Cancer Etiology Cancer Patient Catchment Area Cell Communication Cell Survival Cell physiology Cells Cellular Metabolic Process Cellular Stress Characteristics Chemotherapy-induced peripheral neuropathy Collaborations Community Outreach Complex DNA biosynthesis Dedications Development Developmental Therapeutics Program Diagnostic Drug toxicity Effector Cell Ensure Environment Epigenetic Process Faculty Female Funding Gene Expression Genes Genetic Goals Growth Human Immune Individual Inflammation Invaded K-Series Research Career Programs Lipids Malignant Neoplasms Malignant neoplasm of gastrointestinal tract Malignant neoplasm of lung Malignant neoplasm of prostate Mentors Mentorship Molecular Genetics Molecular Target Mus National Cancer Institute Nature Neoplasm Metastasis Oncoproteins Outcomes Research Pathogenesis Pathway interactions Patients Peer Review Pharmaceutical Preparations Prevention Primary carcinoma of the liver cells Productivity Prognosis Publications Publishing Regulation Regulatory T-Lymphocyte Reporting Research Resistance development Role SPHK1 enzyme Schools Science Scientist Signal Pathway Signal Transduction Strategic Planning Stromal Neoplasm Students Therapeutic Training Translations Tumor-associated macrophages United States National Institutes of Health Universities Virginia Woman Work anticancer research biomarker identification cancer cachexia cancer cell cancer genome cancer prevention cell growth college community engagement endoplasmic reticulum stress ethnic minority gene network immunogenicity innovation inter-institutional malignant breast neoplasm member molecular marker neoplastic cell next generation novel permissiveness prevent programs racial minority resistance mechanism response social health determinants targeted treatment tool transcriptomics translational study treatment response triple-negative invasive breast carcinoma tumor tumor microenvironment tumor progression tumor-immune system interactions tumorigenesis

项目摘要

CANCER BIOLOGY PROGRAM: PROJECT SUMMARY The Virginia Commonwealth University (VCU) Massey Cancer Center (MCC) launched a new Cancer Biology (CB) Program in 2020, incorporating the strengths and expertise of select members from the former Cancer Cell Signaling and Cancer Molecular Genetics Programs. The objective of this restructuring was to build a more cohesive, cancer-centric, basic research program within MCC’s transdisciplinary environment that would enhance collaborative interactions and increase opportunities to seed new scientific concepts. These concepts could be further leveraged through team-based translation with members of the Developmental Therapeutics (DT) or Cancer Prevention and Control (CPC) Programs. CB Program members crafted an overarching scientific pillar goal through the 2021-2025 MCC Strategic Plan to guide their efforts forward – to achieve groundbreaking discoveries through unraveling mechanistic paradigms of tumorigenesis and dissecting key interactions between tumors and their stromal or immune microenvironment. The CB Program is organized under three specific aims focusing on cancer cell signaling, genetic and epigenetic drivers, and tumor microenvironment. CB Program members perform innovative research to understand the complex facets of cancer biology and in collaboration with DT and CPC members develop innovative preventative, diagnostic, and therapeutic tools to target specific cancers, especially those with the highest burden in MCC’s catchment area. Recently, the CB Program undertook initiatives to establish formal collaborations with the Office of Community Outreach and Engagement to ensure its members are fully aware of the distinct characteristics of the cancer burden in MCC’s catchment area so that they can best align their science to address this burden and engage the community in CB Program science going forward. With 47 members across six VCU Schools/Colleges, the CB Program has also cultivated a rich intellectual environment for attracting and mentoring an increasingly diverse pipeline of early-stage cancer biologists. CB Program members currently hold $7.8M in annual, direct, peer-reviewed funding ($3.1M from NCI; $3.3M from other NIH institutes; $1.4M from other agencies). Since 2016, members of the CB Program have published their discoveries in 433 program-relevant and cancer-focused research articles. Demonstrating the program’s collaborative nature, 141 (33%) publications were intra-programmatic, 132 (30%) were inter- programmatic, and 266 (61%) were inter-institutional. Among the many scientific contributions made by CB members since 2016, a few noteworthy include 1) defining the roles of two oncoproteins, AEG-1 and SND1, in hepatocellular carcinoma; 2) discovering a novel Activin/Twist1 axis in cancer cachexia that is amenable to therapeutic manipulation; 3) identifying PDZ1i as a potent anti-metastatic drug; 4) unraveling the ability of sphingosine kinase 1 to inhibit triple-negative breast cancer growth and to suppress chemotherapy-induced peripheral neuropathy; and 5) explicating the correlation of transcriptomic human signatures, based on murine tumor-associated macrophages after ablation of Treg cells, with increased survival in human breast cancer.

癌症生物学项目：项目摘要弗吉尼亚联邦大学 (VCU) 梅西癌症中心 (MCC) 推出了新的癌症生物学 (CB) 2020 年计划，融合了前癌症细胞精选成员的优势和专业知识此次重组的目的是建立一个更加完善的信号传导和癌症分子遗传学项目。 MCC 跨学科环境中的有凝聚力的、以癌症为中心的基础研究项目加强协作互动并增加传播新科学概念的机会。可以通过与发展治疗学成员进行基于团队的翻译来进一步利用 (DT) 或癌症预防和控制 (CPC) 计划成员制定了总体科学计划。通过2021-2025年中冶战略规划的支柱目标来指导他们的努力——实现突破性的进展通过揭示肿瘤发生的机制范式和剖析肿瘤之间的关键相互作用而发现 CB 计划是根据三个具体目标组织的。专注于癌细胞信号传导、遗传和表观遗传驱动因素以及肿瘤微环境。成员进行创新研究，以了解癌症生物学的复杂方面并进行合作与 DT 和 CPC 成员一起开发创新的预防、诊断和治疗工具，以针对特定目标癌症，特别是 MCC 辖区内负担最高的癌症，最近推出了 CB 计划。采取举措与社区外展和参与办公室建立正式合作确保其成员充分了解 MCC 辖区癌症负担的独特特征领域，以便他们能够最好地调整他们的科学来解决这一负担，并使社区参与 CB 计划 CB 计划还培养了来自 VCU 六所学校/学院的 47 名成员。丰富的知识环境，吸引和指导日益多样化的早期癌症治疗渠道 CB 计划成员目前持有 780 万美元的年度直接同行评审资金（其中 310 万美元来自 NCI；自 2016 年以来，CB 计划的成员已从其他 NIH 机构获得 330 万美元；从其他机构获得 140 万美元。在 433 篇与项目相关且以癌症为重点的研究文章中发表了他们的发现。项目的协作性质，141 份 (33%) 出版物是项目内的，132 份 (30%) 是项目间的 CB 做出的众多科学贡献中有 266 项（61%）是跨机构的。自 2016 年以来，一些值得注意的成员包括 1) 定义了两种癌蛋白 AEG-1 和 SND1 在肝细胞癌；2) 在癌症恶病质中发现一种新的 Activin/Twist1 轴治疗操作；3) 鉴定 PDZ1i 作为一种有效的抗转移药物；4) 揭示其能力；鞘氨醇激酶 1 抑制三阴性乳腺癌生长并抑制化疗引起的周围神经病变；5) 基于小鼠解释人类转录组特征的相关性 Treg 细胞消融后的肿瘤相关巨噬细胞在人类乳腺癌中的存活率增加。