Genetic Mechanisms

遗传机制计划摘要 遗传机制计划的科学目标是定义和理解基因变化 以了解这些变化的起源，并利用基因转移 治疗癌症的技术。这些目标包括定义驱动肿瘤启动的具体变化和 进展，导致对肿瘤治疗的抵抗，并影响癌症的易感性。为了实现这些目标， 我们有强大的研究项目，主要集中在以下目标：1)识别癌症易感基因， DNA突变物和转移驱动因素为癌症进展和药物靶点开发新的生物标志物 用于治疗干预；2)了解维持基因组稳定的机制，包括 控制复制压力和DNA损伤耐受性的途径；以及3)开发新一代 将在临床前动物模型中进行测试的病毒和非病毒癌症疗法。遗传机制 该计划是由Anja-Katrin Bielinsky博士和新的联合领导人Masato Yamamoto领导的基础科学计划， 博士和博士，有43名成员，代表19个系和8所学校或学院。别林斯基博士 山本博士负责监督翻译的早期阶段，并协助后续阶段的翻译工作 与转基因以外的临床医生合作，他们是临床试验方面的专家。在上一个预算年度，通用汽车 成员们得到了来自国家癌症研究所的290万美元的直接费用的支持，NIH的其他资金 总计720万美元，同行评审资金总额为1095万美元，所有与癌症相关的资金 赞助来源的直接成本总计为15.2美元。自2013年以来，计划成员发表了634篇论文， 其中17%来自方案内协作，20%来自方案间协作，以及 85%来自外部合作。在过去的资金周期中，我们加强了团队建设努力，以 促进跨越多个主题的领域的研究。揭开促进毒品的机制 实体肿瘤的耐药性是与共济会癌症中心战略计划密切相关的领域之一 增强功能基因组学策略的科学优先增长(SPG2)以加深我们的理解 并开发新的治疗途径。主要成就包括1)小说的验证 预测实体肿瘤无进展生存的生物标记物，2)发现可用药靶点 骨肉瘤，3)产生功能基因组学管道，允许系统地鉴定药物- 耐药途径，以及4)产生第二代溶瘤病毒，将改善 在我们的集水区治疗病人。共济会癌症中心为 方案，包括获得共享资源、招聘新教员、资助26个试点项目 近100万美元，年度研究务虚会，每月计划会议，每周研讨会和每周时事通讯 以促进合作。

Genetic Mechanisms Program Summary The scientific goals of the Genetic Mechanisms Program are to define and understand the genetic changes that occur during cancer development, to understand the genesis of those changes, and to use gene transfer technology to treat cancer. These goals include defining the specific changes that drive tumor initiation and progression, lead to resistance to tumor treatment, and influence cancer susceptibility. To achieve these goals, we feature strong research programs focused on the following Aims: 1) To identify cancer susceptibility genes, DNA mutators, and drivers of metastasis to develop new biomarkers for cancer progression and drug targets for therapeutic intervention; 2) To understand the mechanisms that maintain genome stability, including pathways that control replication stress and DNA damage tolerance; and 3) To develop a new generation of viral and nonviral cancer therapeutics that will be tested in preclinical animal models. The Genetic Mechanisms Program is a basic science program led by Anja-Katrin Bielinsky, PhD, and new co-leader Masato Yamamoto, MD, PhD, and has 43 members, representing 19 departments and 8 schools or colleges. Dr. Bielinsky oversees the early phases of translation, and Dr. Yamamoto assists with later phases and facilitates active collaborations with clinicians outside GM who are experts in clinical trials. For the last budget year, GM members were supported by $2.9 million in direct costs from the National Cancer Institute, other NIH funding totaled $7.2 million, total peer-reviewed funding was $10.95 million, and cancer-related funding from all sponsored sources totaled $15.2 in direct costs. Since 2013, Program members have published 634 papers, 17% of which resulted from intraprogrammatic collaborations, 20% from interprogrammatic collaborations, and 85% from external collaborations. Over the past funding cycle, we enhanced our team-building efforts to promote research in areas that span multiple themes. Uncovering the mechanisms that promote drug resistance in solid tumors is one such area that aligns strongly with the Masonic Cancer Center Strategic Plan Scientific Priority for Growth (SPG2) of enhancing functional genomics strategies to further our understanding of cancer and develop new therapeutic avenues. Major accomplishments include 1) validation of novel biomarkers that predict progression-free survival in solid tumors, 2) uncovering druggable targets in osteosarcoma, 3) generating functional genomics pipelines that allow for the systematic identification of drug- resistance pathways, and 4) generating a second-generation suite of oncolytic viruses that will improve treatment of patients in our catchment area. The Masonic Cancer Center has provided substantial value to the Program, including access to shared resources, recruitment of new faculty, funding of 26 pilot projects for nearly $1M, annual research retreats, monthly Program meetings, weekly seminars, and a weekly newsletter to facilitate collaborations.