University of Kentucky Center for Cancer and Metabolism

项目摘要 癌细胞的存活特征，如抑制的凋亡、快速的细胞周期和增殖， 从原发部位转移需要肿瘤的广泛代谢重编程 微环境有趣的新见解代谢失调在肿瘤发生和发展中的新作用 转移越来越引起人们对目前研究不足的癌症研究领域的关注： 影响治疗结果的代谢调节和代谢事件在临床水平的影响 来影响癌症患者的生活质量。肯塔基州大学（英国）提议建立一个独特的 癌症和代谢（CCM）生物医学研究卓越多学科中心（COBRE）作为一个 战略性设计的可持续框架，培养尖端研究，重点是 癌症发展和进展的代谢介质。拟议的多学科中心利用 在氧化还原生物学、癌细胞信号传导、系统生物化学和数据科学方面具有高度专业化的专业知识， 以及先进的代谢组学和复杂的癌症成像能力的存在， 综合癌症代谢研究框架。总体目标是加强英国的癌症研究 企业通过提供一个主题集中的多学科基础设施，致力于定义 代谢在癌症发展和治疗中的贡献，并利用这一新的多学科 一个平台，培养有前途的早期研究人员，在一个令人兴奋的新癌症领域提高技能 research.为了实现这些目标，我们将（1）培养一批关键的受资助研究人员， 与中心的统一主题直接相关的项目，（2）提供强大的团队指导， 基础和临床专业知识，（3）通过试点项目资助为中心招募新的研究人员 通过机构资金的杠杆作用，（4）通过与强有力的研究的关键联系，在研究项目之间创造协同效应 中心，包括现有的COBREs，以及（5）促进癌症基本发现的翻译 早期的治疗方法。拟议的新协同作用将通过以下四个方面发展： 研究项目，行政核心，重要的研究核心在代谢和成像和强大的 生物统计学/生物信息学支持，所有这些都对拟议的研究至关重要，并将有助于 发展体制资源。这四个研究项目的科学重点是癌症-代谢 跨基础和翻译视角的互动。这种多学科专业知识的集中 关注一个新认识的癌症范例，有望对癌症的 整体肿瘤发生。CCM的综合主题重点和临床和翻译的影响， 对癌症代谢轴的创新理解具有强大的潜力，可以培养出一支训练有素的 科学家们有能力领导未来的科学家们整合这些令人兴奋的新途径， 将代谢失调的研究纳入癌症发展和治疗的多方面研究。

PROJECT SUMMARY Cancer cell survival traits such as suppressed apoptosis, rapid cell cycling and proliferation and the ability to metastasize from a primary location require extensive metabolic reprogramming of the tumor microenvironment. Intriguing new insights into the novel role of metabolic dysregulation in tumorigenesis and metastasis increasingly draw attention to currently understudied areas of cancer research: the potential for metabolic modulation to influence therapeutic outcomes and the impact of metabolic events at the clinical level to impact quality of life for cancer patients. The University of Kentucky (UK) proposes to establish a unique multidisciplinary Center of Biomedical Research Excellence (COBRE) on Cancer and Metabolism (CCM) as a strategically designed, sustainable framework that cultivates cutting-edge research focused on the role of metabolic mediators of cancer development and progression. The proposed multidisciplinary center leverages highly specialized expertise in redox biology, cancer cell signaling, systems biochemistry and data sciences as well as the presence of advanced metabolomics and sophisticated cancer imaging capabilities to create an integrated cancer-metabolism research framework. Overarching goals are to strengthen UK's cancer research enterprise by providing a thematically focused multidisciplinary infrastructure dedicated to defining the contribution of metabolism in the development and treatment of cancer and to use this novel multidisciplinary platform to develop promising early-stage investigators with enhanced skills in an exciting new area of cancer research. To accomplish these goals, we will (1) develop a critical mass of funded investigators with research programs directly related to the Center's unifying theme, (2) provide strong team-based mentoring combining basic and clinical expertise, (3) recruit new investigators to the Center through pilot project grant support leveraged by institutional funds, (4) create synergy among research projects via critical links to strong research centers at UK, including existing COBREs, and (5) facilitate the translation of basic findings in cancer metabolism into early therapeutic approaches. Proposed new synergies will be developed through four research projects, an Administrative Core, important research cores in metabolism and imaging and strong biostatistics/ bioinformatics support, all of which are critical to the proposed studies and will contribute to the development of institutional resources. The scientific focus of the four research projects is cancer-metabolism interactions spanning basic and translational perspectives. This concentration of multidisciplinary expertise focused on a newly recognized cancer paradigm holds promise for significant new understandings of oncogenesis overall. The CCM's integrative thematic focus and the clinical and translational implications of innovative understandings of the cancer-metabolism axis have strong potential to create a cadre of well-trained scientists who are well equipped to lead future generations of scientists integrating these exciting new avenues of investigation in metabolic dysregulation into multi-faceted studies on cancer development and therapy.