Cell Signaling and Metabolism

细胞信号和代谢(CSM)计划项目摘要 更名后的细胞信号和代谢(CSM)计划包含三个中心主题：新目标 发现主题、癌症代谢主题、细胞信号和微环境主题。这个 该计划的科学目标是通过使用多种组学平台更好地了解癌症生物学 以确定和评估新的机会目标和治疗方法。该计划有 通过整合基因组和表观基因组去卷积在新发现中的相当大的力量 方法，结合代谢组学，以告知假定的信号通路。该计划有40个 通过专题小组会议互动的研究成员、23名临床成员、7名附属成员和3名共享成员 和疾病工作组。成员代表16个基础科学和临床科室，包括 分子与人类遗传学、生物化学与分子生物学、分子与细胞生物学、病理学 和免疫学、分子生理学和生物物理学、医学、儿科学、外科和产科以及 妇科。会员关注多种不同的癌症类型，包括胰腺癌、胃肠道癌、肝癌、肺癌、 前列腺癌、膀胱癌、头颈癌。在上一个预算年度，CSM计划总共直接 1420万美元的资金，其中包括420万美元的NCI资金，200万美元来自NIH其他研究所的资金，470万美元 直接来自其他同行审查的资金，340万美元直接来自其他非同行审查的资金。在.期间 在过去的5年里，计划成员共发表了706篇稿件，其中24%来自于内部 方案协作，18%是方案间协作，73%是机构间协作。几个 出版物和联合资助是通过加强成员之间的沟通努力而产生的 主题组与小组互动。特别是，已经作出了相当大的努力，今后的计划包括使用 识别代谢调节的靶向改变信号通路的多组学方法 审问。这包括重点识别泛癌症的改变。这些努力也是基于集水区。 区域问题，特别是吸烟和肥胖症。此外，相当大的努力集中在确定 造成医疗保健差距的生物机制。未来的方向包括扩大正式职业生涯 通过加强沟通和计划，加强和培训学员的教育工作。具体目标是：1. 识别和表征相互重叠的分子基础和调节代谢的途径 重新布线以描绘与癌症发生和进展相关的关键常见分子介质。2.至 评估可操作的信号通路和生物靶点，这些信号通路和生物靶点是代谢和 癌症进展的分子介体。3.通过与以下机构的互动，制定关键调查结果的翻译 药物发现中心、治疗创新中心和疾病工作组，以促进 开发新的诊断、预后和治疗方法。

CELL SIGNALING AND METABOLISM (CSM) PROGRAM PROJECT SUMMARY The renamed Cell Signaling and Metabolism (CSM) Program incorporates three central Themes; New Target Discovery Theme, Cancer Metabolism Theme, and the Cell Signaling and the Microenvironment Theme. The scientific goals of the Program are to better understand cancer biology through use of multi-omics platforms in order to identify and assess new targets of opportunity and therapeutic approaches. The Program has considerable strength in new discovery through integration of genomic and epigenomic deconvolution approaches, coupled together with metabolomics to inform on putative signaling pathways. The Program has 40 Research members, 23 Clinical, 7 Adjunct and 3 Shared members who interact via thematic subgroup meetings and the Disease Working Groups. Members represent 16 basic science and clinical departments, including Molecular and Human Genetics, Biochemistry and Molecular Biology, Molecular and Cellular Biology, Pathology and Immunology, Molecular Physiology and Biophysics, Medicine, Pediatrics, Surgery, and Obstetrics and Gynecology. Members focus on multiple different cancer types including pancreas, gastrointestinal, liver, lung, prostate, bladder, and head and neck cancers. During the last budget year, the CSM Program had a total direct funding of $14.2 million that included $4.2 million in NCI funding, $2 million from other NIH institutes, $4.7 million direct in other peer-reviewed funding, and $3.4 million direct from other non-peer reviewed funding. During the previous 5 years, Program members have published a total of 706 manuscripts with 24% resulting from intra- programmatic collaborations, 18% inter-programmatic, and 73% from inter-institutional collaborations. Several publications and joint funding have resulted from an enhanced communication effort between members via thematic subgroup interactions. In particular, considerable effort has been made and future plans include use of multi-omic approaches to identify targetable altered signaling pathways that are informed by metabolic interrogation. This includes a focus to identify pan-cancer alterations. These efforts are also based on catchment area issues, including smoking and obesity, in particular. In addition, considerable effort is focused on identifying biological mechanisms that underlie health care disparity. Future directions include expanding formal career enhancement and trainee educational efforts via enhanced communication and programs. Specific Aims are: 1. To identify and characterize the overlapping molecular underpinnings and pathways regulating metabolic rewiring to delineate key common molecular mediators associated with cancer onset and progression. 2. To evaluate actionable signaling pathways and biological targets that are causal or a consequence of metabolic and molecular mediators of cancer progression. 3. To enact translation of key findings through interactions with the Center for Drug Discovery, the Therapeutic Innovation Center, and the Disease Working Groups to foster development of novel diagnostic, prognostic, and therapeutic approaches.