CBIO - Project

CBIO - 项目

• 批准号: 10332946
• 负责人: JOHN Hackett BUSHWELLER
• 金额: $ 2.42万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-16 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10332946
• 关键词: Acute Myelocytic Leukemia; Adenoid Cystic Carcinoma; Agammaglobulinaemia tyrosine kinase; Antineoplastic Agents; Area; Automobile Driving; Basic Science; Biochemistry; Biology; Cancer Biology; Cancer Center; Cancer Center Support Grant; Catchment Area; Cells; Chemicals; Chromosomes; Chronic Lymphocytic Leukemia; Clinic; Clinical Trials; Collaborations; Cryoelectron Microscopy; Development; Diacylglycerol Kinase; Direct Costs; Disease; Endothelial Cells; Epigenetic Process; Exposure to; Feeds; Flow Cytometry; Funding; Genetic; Goals; Grant; Head and Neck Squamous Cell Carcinoma; Homeostasis; Individual; Industry; Knock-out; Knowledge; Lead; Lipids; Malignant Neoplasms; Mantle Cell Lymphoma; Methods; Microscopy; Molecular; Molecular Genetics; Multi-Institutional Clinical Trial; Mutagenesis; Mutation; Neoplasm Metastasis; Normal tissue morphology; Pathway interactions; Peer Review; Pharmacology; Phosphotransferases; Pre-Clinical Model; Principal Investigator; Proteins; Publications; Research; Research Personnel; Resource Sharing; Schools; Science; Signal Transduction; Site; Structure; Systems Biology; Therapeutic; Therapeutic Intervention; Tissues; Training and Education; Translational Research; United States National Academy of Sciences; University of Virginia Cancer Center; Validation; Work; acronyms; anticancer research; base; biobank; cancer heterogeneity; cancer therapy; cancer type; clinical application; design; drug development; drug discovery; experience; inhibitor; insight; knock-down; malignant breast neoplasm; member; new therapeutic target; novel; novel therapeutic intervention; novel therapeutics; programs; receptor; research facility; small molecule; small molecule therapeutics; structural biology; therapeutic development; therapeutic target; tool development; transcription factor; tumor; tumor initiation; tumor microenvironment

CANCER BIOLOGY (CBIO) – PROJECT SUMMARY/ABSTRACT A critical need remains for new therapies to treat various types of cancer. The discovery of new therapies begins with uncovering the basic mechanisms that drive cancer, identifying the critical components of those mechanisms, and then subsequently targeting them with small molecules that act as drugs for cancer therapy. The Cancer Biology (CBIO) program exists to unite University of Virginia Cancer Center (UVACC) investigators whose research programs collectively make discoveries about mechanisms that drive cancer and advance that knowledge through to the identification of therapeutic targets and development of small molecule modulators to interfere with these targets. The CBIO program has a robust research base of investigators working to elucidate mechanisms driving cancer, particularly with respect to how various signaling networks contribute to tumor initiation and metastasis (Aim 1) and to validate individual proteins in tumors as targets for small molecule modulators and identify or develop small molecule modulators of validated targets in cancers (Aim 2). Investigators work to develop an understanding about how receptors and intracellular signaling support homeostasis in normal tissues and how mutations perturb these networks. These efforts are critical to identify pathways that represent vulnerabilities in particular cancers leading to new targets for validation and development of small molecule modulators. The identification of novel targets feeds subsequent efforts to move small molecule therapeutics further along the pipeline toward clinical application in conjunction with the Cancer Therapeutics Program (CRX). The CBIO program has two co-leaders: Bushweller leverages his expertise in chemical and structural biology within the Program to support and enhance cancer research; Gioeli's experience in industry developing a novel pre-clinical model for target identification, validation, and drug discovery enables him to support CBIO Program goals. The Program consists of 53 members, 17 of whom are new to UVA or the UVACC, from 10 departments and three schools. The Program Members are principal investigators of grants totaling $12.83M of current direct cost peer-reviewed funding with $3.29M from NCI and $9.54M from other agencies. Twelve CBIO Program Members participate in one or more of the disease-specific Translational Research Teams, which were created to spawn research in cancers that are over-represented in the UVACC catchment area; three CBIO members serve as basic science co-leaders, thus leveraging basic science expertise to advance research in cancers of particular relevance. CBIO Members depend on the Shared Resources provided by the UVACC, particularly the Advanced Microscopy Facility, the Biomolecular Analysis Facility, the Biorepository and Tissue Research Facility, and the Flow Cytometry Core. Together, these activities culminated in 236 selected publications since the last grant period. Of these, 34% have an impact factor of 10 or greater, 19% are intra-programmatic, 27% are inter-programmatic with other UVACC Programs, and 21% are collaborative with other NCI Cancer Centers.

癌症生物学 (CBIO) – 项目摘要/摘要 仍然迫切需要治疗各种类型癌症的新疗法。 首先揭示导致癌症的基本机制，确定这些机制的关键组成部分 机制，然后用作为癌症治疗药物的小分子来靶向它们。 癌症生物学 (CBIO) 项目的存在是为了联合弗吉尼亚大学癌症中心 (UVACC) 的研究人员 他们的研究项目共同发现了驱动癌症的机制并推动了癌症的发展 知识通过识别治疗靶点和开发小分子调节剂来 CBIO 计划拥有强大的研究人员研究基础，致力于干扰这些目标。 阐明癌症的驱动机制，特别是各种信号网络如何促进癌症 肿瘤的发生和转移（目标 1），并验证肿瘤中的单个蛋白质作为小分子的靶点 分子调节剂，并识别或开发癌症中经过验证的靶点的小分子调节剂（目标 2）。 研究人员致力于了解受体和细胞内信号传导如何支持 正常组织中的稳态以及突变如何扰乱这些网络对于识别这些网络至关重要。 代表特定癌症脆弱性的途径，导致新的验证目标和 小分子调节剂的开发促进了后续的努力。 推动小分子疗法进一步走向临床应用 癌症治疗计划 (CRX) 有两位联合领导者：布什韦勒利用他的优势。 该计划内化学和结构生物学方面的专业知识，以支持和加强癌症研究； Gioeli 在开发用于目标识别、验证和评估的新型临床前模型方面拥有丰富的行业经验 药物发现使他能够支持 CBIO 计划的目标。该计划由 53 名成员组成，其中 17 名成员。 来自 UVA 或 UVACC 的新成员，来自 10 个院系和 3 所学校。 主要研究人员的赠款总额为 1283 万美元，当前直接成本同行评审资金中的 329 万美元来自 NCI 和其他机构的 954 万美元参与其中一项或多项。 特定疾病的转化研究团队，其成立的目的是对癌症进行研究 在 UVACC 流域中代表性过高；三名 CBIO 成员担任基础科学联合领导者，因此 利用基础科学专业知识推进特别相关的癌症研究。 依赖于 UVACC 提供的共享资源，特别是先进的显微镜设施、 生物分子分析设施、生物样本库和组织研究设施以及流式细胞术核心。 自上次资助期以来，这些活动总共产生了 236 份选定的出版物，其中 34%。 影响因子为 10 或更高，19% 是程序内的，27% 是与其他程序间的 UVACC 项目，21% 与其他 NCI 癌症中心合作。