Molecular Oncology Research Program

分子肿瘤学（MO）研究 项目总结/摘要 分子肿瘤学（MO）研究计划是病例综合研究的基础科学支柱。 癌症中心（病例CCC）。该计划是家庭对基础科学家的各种群体与广泛的 包括当代癌症研究的兴趣。该计划中的特殊专业知识范围 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，以及国家认可的疾病特异性 脑肿瘤和乳腺癌的研究。该计划的首要目标是阐明基本的 肿瘤发生的机制，包括癌症干细胞调节，DNA损伤 修复和宿主-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 基因组不稳定性和改变治疗反应，（3）揭示促进肿瘤发生的关键宿主-肿瘤相互作用。 肿瘤进展和治疗抗性。这些目标支持MO计划的关键功能， 作为一个孵化器，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。主要的工作组和倡议，联合计划成员， 其他癌症中心的研究人员通过跨项目合作，导致临床前和临床 研究成果、赠款和试验方案。广泛使用各种共享资源，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了成员的各个方面 发现。 在Alex Almasan（联合负责人）和Bing-Cheng Wang（联合负责人）的领导下，MO计划已 53名成员，包括44名正式成员，8名助理成员和1名临床成员。委员来自十八个部门， 每年的研究补助金直接费用总额为1470万美元，其中1420万美元是同行评审的， 670万美元的国家癌症研究所资助。2012年至2016年，MO计划成员发表了716篇出版物。癌症和 与计划相关的出版物包括37%的计划间出版物，19%的计划内出版物，9%的计划间和计划内出版物。 7%涉及与另一个癌症中心的合作。这个高效的项目 在当代癌症研究中取得了重大进展例如：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;阐明了有丝分裂 驱动蛋白KIF 11是胶质母细胞瘤侵袭、增殖和自我更新的驱动因子; 揭示了胶质母细胞瘤干细胞样细胞中的优先铁运输;检查减数分裂配对的控制 以及通过染色体栓系的26 S蛋白酶体进行重组;发现胶质母细胞瘤干细胞 分泌骨膜蛋白以募集肿瘤相关巨噬细胞。

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.