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 新疗法的关键需求仍然是治疗各种类型癌症的需求。发现新疗法 首先要发现驱动癌症的基本机制，从 机制，然后用小分子作为癌症治疗的药物来靶向。 癌症生物学（CBIO）计划统一弗吉尼亚大学癌症中心（UVACC）研究人员 他们的研究计划共同发现了驱动癌症的机制，并推进了 通过识别治疗靶标的知识和小分子调节剂的发展 干扰这些目标。 CBIO计划的研究基础是研究人员的研究基础 阐明驱动癌症的机制，尤其是在各种信号网络如何贡献的方面 肿瘤倡议和转移（AIM 1），并验证肿瘤中的单个蛋白质作为小的靶标 分子调节剂并识别或开发癌症中经过验证靶标的小分子调节剂（AIM 2）。 调查人员努力发展有关接收器和细胞内信号支持的理解 正常组织中的稳态以及突变如何扰动这些网络。这些努力对于确定 代表漏洞的途径，特别是癌症，导致新目标进行验证和 小分子调节剂的发展。新目标的识别将随后的努力供应 沿着管道将小分子疗法进一步移动到临床应用以及 癌症治疗计划（CRX）。 CBIO计划有两个共同领导者：丛林居民利用他的 该计划内化学和结构生物学方面的专业知识，以支持和增强癌症研究； Gioeli在行业方面的经验开发了一种新颖的临床前模型，用于目标识别，验证和 药物发现使他能够支持CBIO计划目标。该计划由53名成员，17名成员组成 来自UVA或UVACC的新手，来自10个部门和3所学校。计划成员是 赠款的主要调查员总计1.283亿美元的当前直接成本经过同行评审的资金，32.9万美元 NCI和其他机构的954万美元。十二名CBIO计划成员参加了一个或多个 特定于疾病的转化研究团队是为了在癌症中产生研究的创建 UVACC集水区的代表性过多；三名CBIO成员是基础科学共同领导者，因此 利用基础科学专业知识来促进特定相关性的癌症研究。 CBIO成员 取决于UVACC提供的共享资源，特别是高级显微镜设施， 生物分子分析设施，生物座和组织研究设施以及流式细胞仪核心。 自上次赠款时期以来，这些活动共同达到了236个选定的出版物。其中34％ 具有10或更高的影响因子，19％是概括性的，27％与其他 UVACC计划，21％与其他NCI癌症中心合作。