Molecular Oncology Research Program

分子肿瘤学研究计划

• 批准号: 10380714
• 负责人: Justin D. Lathia
• 金额: $ 5.07万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10380714
• 关键词: 26S proteasome; Address; Award; Basic Science; Biometry; Blood Vessels; Brain Neoplasms; Breast; Cancer Center; Cancer Center Support Grant; Cancer Control; Catchment Area; Cell Proliferation; Cell-Matrix Junction; Cells; Clinical; Clinical Research; Clinical Trials; Collaborations; Comprehensive Cancer Center; Cytometry; DNA Damage; DNA Repair; Defect; Development; Devices; Direct Costs; Disease; Down-Regulation; Drug resistance; Foundations; Funding; Gene Expression Regulation; Genetic Recombination; Genomic Instability; Glioblastoma; Glioma; Goals; Grant; Head and Neck Cancer; Home; Hyperthermia; Image; Immune Evasion; Incubators; Integrins; Investigation; Iron; Journals; Kinesin; Leadership; Maintenance; Malignant Neoplasms; Malignant neoplasm of gastrointestinal tract; Meiosis; Mitotic; Molecular; Mus; Nature; Normal Cell; Obesity; Obesity associated cancer; Pathway interactions; Peer Review; Pericytes; Phenotype; Population; Population Research; Prevalence; Productivity; Program Research Project Grants; Proteins; Proteomics; Protocols documentation; Publications; Publishing; Radiation-Sensitizing Agents; Radiosensitization; Regulation; Research; Research Personnel; Research Project Grants; Research Support; Resource Sharing; Role; Schedule; Science; Scientist; Signal Transduction; Stem Cell Development; TLR4 gene; Translations; Tumor Cell Invasion; Tumor-associated macrophages; Vertebral column; angiogenesis; anticancer research; base; cancer cell; cancer genetics; cancer imaging; cancer prevention; cancer stem cell; cancer therapy; catalyst; cell motility; cell type; fatty acid metabolism; host neoplasm interaction; interest; macromolecule; malignant breast neoplasm; member; molecular oncology; multicatalytic endopeptidase complex; neoplastic cell; novel; novel strategies; novel therapeutics; oncology program; periostin; pre-clinical research; precision medicine; programs; recruit; response; self-renewal; stem cell biology; stem cells; stem-like cell; symposium; therapy resistant; tissue resource; trafficking; transdifferentiation; translational cancer research; treatment response; tumor; tumor growth; tumor heterogeneity; tumor microenvironment; tumor progression; tumorigenesis; tumorigenic; working group

MOLECULAR ONCOLOGY (MO) RESEARCH PROGRAM PROJECT SUMMARY/ABSTRACT The Molecular Oncology (MO) Research Program is the basic science backbone of the Case Comprehensive Cancer Center (Case CCC). The program is home to diverse groups of basic scientists with a wide spectrum of interests that encompass contemporary cancer research. The exceptional expertise in the Program ranges from fundamental cell signaling mechanisms, to structural elucidation of macromolecules, to cancer stem cell biology and DNA damage response, tumor microenvironments, and nationally recognized disease-specific groups in brain tumors and breast cancer. The Program's overarching goal is to elucidate fundamental mechanisms of oncogenesis, encompassing the general themes of cancer stem cell regulation, DNA damage and repair, and host-tumor interactions. This is organized around 3 scientific aims: (1) Discover cancer stem cell mechanisms for cancer prevention and treatment; (2) Identify how defective DNA damage repair promotes genomic instability and alters therapeutic response and, (3) Reveal key host-tumor interactions that promote tumor progression and therapeutic resistance. These aims support the key function of the MO program to serve as an incubator to develop and nurture new research initiatives expected to mature into new research themes within the Center. The major working groups and initiatives that coalesces program members with other cancer center investigators through interprogrammatic collaborations that result in preclinical and clinical research efforts, grants, and trial protocols. Extensive use of an array of shared resources, in particular Cytometry, Imaging, Tissue Resources, Proteomics, and Biostatistics facilitate all aspects of member discoveries. Under the leadership of Alex Almasan (Co-Leader) and Bing-Cheng Wang (Co-Leader) the MO Program has 53 members including 44 full, 8 associate, and 1 clinical member. Members represent 18 departments and are funded with a total of $14.7M in annual research grant direct costs, $14.2M of which is peer-reviewed and $6.7M NCI-funded. Between 2012 and 2016, MO program members published 716 publications. Cancer and program related publications included 37% inter-programmatic, 19% intra-programmatic, 9% inter- and intra- programmatic and 7% that involved collaborations with another cancer center. This highly effective program has made major advances to contemporary cancer research. Examples include: discovery that glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth; elucidation that the mitotic kinesin KIF11 is a driver of invasion, proliferation, and self-renewal in glioblastoma; identification of the revealed preferential iron trafficking in glioblastoma stem-like cells; examination of the control of meiotic pairing and recombination by chromosomally tethered 26S proteasome; and the discovery that glioblastoma stem cells secrete periostin to recruit tumor-associated macrophages.

分子肿瘤学 (MO) 研究计划 项目概要/摘要 分子肿瘤学（MO）研究计划是案例综合的基础科学支柱 癌症中心（案例 CCC）。该计划是不同基础科学家群体的家园，他们具有广泛的研究背景 涵盖当代癌症研究的兴趣。该计划范围内的卓越专业知识 从基本的细胞信号传导机制，到大分子的结构阐明，再到癌症干细胞 生物学和 DNA 损伤反应、肿瘤微环境和国家认可的疾病特异性 脑肿瘤和乳腺癌组。该计划的总体目标是阐明基本原理 肿瘤发生机制，涵盖癌症干细胞调节、DNA 损伤等一般主题 和修复以及宿主-肿瘤相互作用。这是围绕 3 个科学目标组织的：(1) 发现癌症干细胞 癌症预防和治疗的细胞机制； (2) 确定缺陷DNA损伤修复如何促进 基因组不稳定性并改变治疗反应，(3) 揭示促进宿主-肿瘤相互作用的关键 肿瘤进展和治疗抵抗。这些目标支持 MO 计划的关键功能： 作为孵化器来开发和培育新的研究计划，预计将成熟为新的研究 中心内的主题。将计划成员联合起来的主要工作组和倡议 其他癌症中心研究人员通过项目间合作进行临床前和临床研究 研究工作、资助和试验方案。广泛使用一系列共享资源，特别是 细胞计数、成像、组织资源、蛋白质组学和生物统计学促进会员的各个方面 发现。 在 Alex Almasan（联合领导者）和 Bing-Cheng Wang（联合领导者）的领导下，MO 项目已 53 名会员，其中 44 名正式会员、8 名准会员和 1 名临床会员。成员代表18个部门，分别是 年度研究补助金直接费用总计 1,470 万美元，其中 1,420 万美元经过同行评审和 NCI 资助 670 万美元。 2012 年至 2016 年间，MO 计划成员发表了 716 篇出版物。癌症和 计划相关出版物包括 37% 计划间出版物、19% 计划内出版物、9% 计划间和计划内出版物 计划性的，7% 涉及与另一个癌症中心的合作。这个非常有效的计划 为当代癌症研究取得了重大进展。例子包括：发现胶质母细胞瘤 干细胞产生血管周细胞以支持血管功能和肿瘤生长；阐明有丝分裂 驱动蛋白 KIF11 是胶质母细胞瘤侵袭、增殖和自我更新的驱动因素；的识别 揭示了胶质母细胞瘤干细胞样细胞中铁的优先运输；减数分裂配对控制的检查 以及通过染色体束缚的 26S 蛋白酶体进行重组；以及胶质母细胞瘤干细胞的发现 分泌骨膜素来招募肿瘤相关巨噬细胞。