Molecular Oncology Research Program

分子肿瘤(MO)研究计划 项目摘要/摘要 分子肿瘤学(MO)研究计划是Case Complex的基础科学支柱 癌症中心(Case CCC)。该计划是不同的基础科学家群体的家园，他们的范围很广 包括当代癌症研究的兴趣。计划范围内的卓越专业知识 从基本的细胞信号机制，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、肿瘤微环境和国家公认的疾病特异性 脑瘤和乳腺癌的人群。该计划的首要目标是阐明基本原理 肿瘤发生机制，包括癌症干细胞调控、DNA损伤等一般主题 和修复，以及宿主和肿瘤的相互作用。这是围绕三个科学目标组织的：(1)发现癌症干细胞 癌症预防和治疗的细胞机制；(2)识别DNA损伤修复缺陷如何促进 基因组不稳定和改变治疗反应，以及，(3)揭示促进 肿瘤进展与治疗耐药。这些目标支持了MO计划的关键功能 作为孵化器，开发和培育有望成熟为新研究的新研究计划 中心内的主题。将计划成员联合在一起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，导致临床前和临床 研究成果、拨款和试验方案。广泛使用一系列共享资源，特别是 细胞学、成像、组织资源、蛋白质组学和生物统计学促进成员的方方面面 发现。 在亚历克斯·阿尔马桑(联席负责人)和程望(联席负责人)的领导下，MO计划 会员53人，其中正式会员44人，准会员8人，临床会员1人。成员代表18个部门，包括 资助总额为1,470万美元的年度研究补助金直接费用，其中1,420万美元为同行评审和 670万美元由NCI提供资金。2012至2016年间，MO计划成员出版了716份出版物。癌症和 与方案有关的出版物包括37%的方案间出版物，19%的方案内出版物，9%的方案间和方案内出版物 计划性的和7%的涉及与另一家癌症中心的合作。这个非常有效的计划 在当代癌症研究方面取得了重大进展。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；阐明有丝分裂 KIF11是胶质母细胞瘤侵袭、增殖和自我更新的驱动力；鉴定 揭示了胶质母细胞瘤干细胞中铁的优先转运；减数分裂配对控制的检查 并通过染色体拴系的26S蛋白酶体重组；以及胶质母细胞瘤干细胞的发现 分泌Periostin以招募肿瘤相关巨噬细胞。

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.