Stanford Cancer Institute

 描述（由申请人提供）：癌症生物学计划的重点是研究恶性转化的机制和信号通路。其目标是推进对癌症发病机制的基本理解，并通过合作促进基础科学发现转化为临床竞技场，以改善癌症患者的预后。项目研究围绕三大科学主题： 主题1：肿瘤发生的机制和途径。研究重点是癌基因和肿瘤抑制基因的机制分析，以及细胞分裂，基因组稳定性和DNA损伤检查点的控制，这些都是癌症发病机制的基础和驱动力。 主题2：表观遗传学。正在采用不同的方法来研究表观遗传因素和扰动，这些因素和扰动越来越多地与广泛的恶性肿瘤相关，特别关注维持和读取组蛋白密码的因素，以及染色质重塑机制和具有表观遗传相关性的IncRNA。 主题3：上皮性肿瘤。正在使用各种体外和体内模型系统研究实体瘤（包括肺、GI、皮肤和GU瘤形成）的分子和细胞生物学。在此资助期内的主要成就包括滑膜肉瘤中致癌BAF融合蛋白的表征，用于评估全基因组染色质可及性的新技术的推导，表观遗传lncRNA的发现和表征，类器官培养物中新癌基因的验证，MAPK通路的支架靶向，以及Hedgehog（Hh）信号通路中新下游靶点的鉴定。 由医学博士Michael Cleary和医学博士卡尔文郭共同领导，40名项目成员代表三所学校（医学院，人文科学学院和工程学院），14个部门和医学系内的五个部门。40名研究人员的研究活动得到了80个同行评审的赠款和3个T32培训奖的支持。同行评审的资金包括每年2810万美元的总成本，其中950万美元来自NCI。其他NIH支持金额为1650万美元，其他同行评审支持金额为210万美元。自2009年以来，项目研究人员在同行评审期刊上发表了280多篇与癌症生物学相关的手稿，其中15%是项目内的，48%是项目间的，还有许多外部合作的手稿。SCI将继续在播种创新项目方面发挥宝贵作用，并协助将该项目的基础科学发现转化为诊断和治疗癌症患者的新方法。

 DESCRIPTION (provided by applicant): The Cancer Biology Program is focused on investigating the mechanisms and signaling pathways involved in malignant transformation. The goals are to advance basic understanding of cancer pathogenesis and to facilitate the translation of basic science discoveries into the clinical arena through collaborations to improve the outcome of patients with cancer. Program research centers on three major scientific themes: Theme 1: Mechanisms and Pathways of Oncogenesis. Investigations are focused on mechanistic analyses of oncogenes and tumor suppressor genes, as well as the control of cell division, genomic stability and DNA damage checkpoints that underlie and drive cancer pathogenesis. Theme 2: Epigenetics. Diverse approaches are being employed to investigate the epigenetic factors and perturbations that are increasingly associated with a wide spectrum of malignancies, with a particular focus on factors that maintain and read the histone code, as well as the chromatin remodeling machinery and IncRNAs that have epigenetic relevance. Theme 3: Epithelial Neoplasia. The molecular and cellular biology of solid tumors, including lung, GI, skin and GU neoplasias, are being investigated using a variety of in vitro and in vivo model systems. Major achievements in this funding period include characterization of oncogenic BAF fusion proteins in synovial sarcomas, derivation of novel techniques for assessing genome-wide chromatin accessibility, discovery and characterization of epigenetic lncRNAs, validation of novel oncogenes in organoid cultures, scaffold targeting of the MAPK pathway, and identification of new downstream targets in the Hedgehog (Hh) signaling pathway. Co-led by Michael Cleary, MD, and Calvin Kuo, MD, PhD, the 40 program members represent three schools (the School of Medicine, the School of Humanities & Sciences and the School of Engineering), 14 Departments, and five Divisions within the Department of Medicine. The research activities of the 40 investigators are supported by 80 peer-reviewed, investigator-initiated grants and 3 T32 training awards. Peer-reviewed funding consists of $28.1M in total costs/year of which $9.5M is from the NCI. Other NIH support amounts to $16.5M and other peer-reviewed support to $2.1M. Since 2009, program investigators have published over 280 manuscripts relevant to cancer biology in peer-reviewed journals of which 15% are intra-programmatic and 48% inter-programmatic, with numerous externally collaborative manuscripts. The SCI will continue to be invaluable in seeding innovative projects and in assisting with the translation of the basic science findings from this program into new approaches to the diagnosis and treatment of patients with cancer.