CANCER CELL BIOLOGY

癌症细胞生物学(CB)项目的成员研究细胞周期、信号转导、细胞凋亡、细胞发育、细胞分化、干细胞生物学、免疫和炎症反应以及转移。 他们致力于确定癌症中这些过程的驱动因素，并将这些知识转化为癌症患者的潜在生物标记物和治疗方法和靶点。该计划开发的解决这些领域的新技术和方法包括研究癌症干细胞、信号和凋亡的简易动物模型、独特的肿瘤表观遗传修饰的质谱分析、功能性基因组药物筛选和癌症疫苗开发。 CB有四个相互关联的焦点组：1)信号转导与凋亡；2)细胞周期调控与增殖；3)发育、干细胞与癌症；4)炎症、免疫与转移。 在之前的资助期间，CB在该领域做出了重大贡献，包括：1)利用青蛙模型系统(Repo-Man)发现了一个新的癌基因；2)确定了水飞蓟宾(IP6)的作用机制；3)根据信号转导、细胞凋亡和细胞周期途径(如Mer TK和p27靶点)的知识开发了新的治疗药物；4)研究了IL-1b介导的炎症在黑色素瘤转移中的作用；5)发现了新的表观遗传学标记(组蛋白H3K56)；6)证明了功能突变的p53获得比p53缺失带来的预后更差；并且，7)使用新的动物模型(皮肤中的BCR和MYC)来检验癌症干细胞假说。 CB在科罗拉多大学丹佛大学、科罗拉多大学博尔德大学、国家犹太人健康中心和科罗拉多州立大学校园的20个系和6所学校拥有66名正式成员，在上一个预算年度拥有270万美元的NCI赠款直接成本和2370万美元的其他癌症相关支持的直接成本。2005至2010年间，人均癌症研究经费从28.6万美元增加到40万美元，增幅达40%。从2005年到2010年，CB出版了869份与癌症相关的出版物。在这些出版物中，230份(26.5%)是方案间出版物；66份(7.6%)是方案内出版物；36份(4%)既是方案间出版物，也是方案内出版物。因此，在该项目成员发表的与癌症相关的全部出版物中，有332篇(38%)是合作的。重要的是，超过三分之二的CB成员在上个资助期发表了与其他UCCC成员合作的同行评议论文。

Members of the Cancer Cell Biology (CB) Program study the cell cycle, signal transduction, apoptosis, cell development, cell differentiation, stem cell biology, immune and inflammatory responses and metastasis. They are engaged in determining the drivers of these processes in cancer and translating this knowledge into potential biomarkers and therapeutic approaches and targets for cancer patients. Novel technologies and approaches to address these areas developed by the program include facile animal models to study cancer stem cells, signaling and apoptosis, mass spectrometric analysis of unique tumor epigenetic modifications, functional genomic drug screens and cancer vaccine development. CB has four interconnected focus groups: 1) Signal Transduction and Apoptosis; 2) Cell Cycle Regulation and Proliferation; 3) Development, Stem Cells and Cancer; 4) Inflammation, Immunity and Metastasis. In the prior funding period, CB made major contributions to the field, including: 1) Identified a novel oncogene using a frog model system (Repo-Man); 2) Determined the mechanism of action of Silibinin (IP6) a chemopreventive compound; 3) Developed novel therapeutics from knowledge of signal transduction, apoptosis and cell cycle pathways (e.g. Mer TK and p27 targets); 4) Investigated IL-lb-mediated inflammation's role in melanoma metastasis; 5) Discovered novel epigenetic markers (histone H3 K56); 6) demonstrated the p53 gain of function mutations confer a worse prognosis than p53 deletion; and, 7) Tested the cancer stem cell hypothesis using novel animal models (BCR and MYC in skin). CB has 66 full members in 20 Departments and 6 schools on the University of Colorado Denver, University of Colorado Boulder, National Jewish Health, and the Colorado State University campuses holding $2.7 million direct costs in NCI grants and $23.7 million direct costs in other cancer-relevant support in the last budget year. Between 2005 and 2010, per capita cancer research funding increased by 40% from $286K to over $400K. CB produced 869 cancer-related publications from 2005 through 2010. Of these, 230 (26.5%) were inter-programmatic publications; 66 (7.6%) were intra-programmatic publications; and 36 (4%) were both inter- and intra-programmatic. Thus, 332 (38%) of the total cancer-related publications by memtjers of this program were collaborative. Importantly, more than 2/3 of CB members published collaborative peer reviewed papers in the last funding period with other UCCC members.