Stanford Cancer Institute

 描述(由申请者提供)：癌症生物学专业致力于研究恶性转化的机制和信号通路。其目标是通过合作促进对癌症发病机制的基本了解，并促进将基础科学发现转化为临床领域，以改善癌症患者的结局。项目研究围绕三个主要科学主题展开： 主题1：肿瘤发生的机制和途径。研究集中在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，这些都是癌症发病的基础和驱动因素。 主题2：表观遗传学。人们正采用不同的方法来研究与多种恶性肿瘤相关的表观遗传因素和扰动，尤其是维持和读取组蛋白密码的因素，以及与表观遗传相关的染色质重塑机制和IncRNA。 主题3：上皮性肿瘤。实体肿瘤的分子和细胞生物学，包括肺、胃肠道、皮肤和胃肠道肿瘤，正在使用各种体外和体内模型系统进行研究。这一资助期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衍生、表观遗传学lncRNAs的发现和表征、在类器官培养中新癌基因的验证、MAPK通路的支架靶向以及Hedgehog(HH)信号通路中新的下游靶点的确定。 由医学博士Michael Cleary和医学博士Calvin Kuo共同领导的40个项目成员分别代表3个学院(医学院、人文科学学院和工程学院)、14个系和医学系内的5个分部。40名调查员的研究活动得到80名同行评议的调查员发起的赠款和3名T32培训奖的支持。同行审查的资金包括2810万美元的总成本/年，其中950万美元来自NCI。美国国立卫生研究院的其他资助金额为1650万美元，其他同行评审的资助金额为210万美元。自2009年以来，项目调查人员已在同行评议期刊上发表了280多篇与癌症生物学相关的手稿，其中15%是计划内的，48%是计划间的，还有大量外部合作的手稿。SCI将继续为创新项目提供种子，并协助将该项目的基本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.