Genomic Instability, Epigenetics and Metabolism Research Program

项目总结/摘要 基因组不稳定性，表观遗传学和代谢（GEM）研究计划代表了重组 和前氧化还原损伤和修复（RR）研究计划的计划扩展，以反映 在高度互补的研究领域拥有专业知识的参与成员的研究实力不断增强 推力GEM研究工作是Markey癌症中心（MCC）整体使命的核心， 在肯塔基州，周边社区和国家的癌症负担。GEM研究人员确定遗传， 表观遗传和代谢机制，促进癌症发展，燃料肿瘤进展， 有助于治疗抗性。该计划的总体目标是全面了解 这些过程的基本机制，以促进发展的新的和合理的方法， 癌症预防和治疗。为了实现这一目标，GEM确立了三个相互关联的主题：1）研究 研究基因组不稳定性和DNA修复将确定先天DNA修复途径如何与 环境诱变剂对致癌作用的影响; 2）恶性肿瘤表观遗传机制的研究将 描述表观基因组和基因转录的改变如何影响致癌作用;以及3）研究 癌症代谢重编程将破译的作用，代谢过程，有助于癌症 发展重点是线粒体功能和氧化还原介导的失调。主题是 概念上的联系，并具有强大的教师协作。创业板计划的成员是先驱和专家 在氧化还原生物学、DNA修复、表观遗传调控和癌症代谢方面。该计划包括18个 成员来自6个部门在医学院和艺术和科学。这个项目是癌症 相关资金每年总资金超过490万美元（330万美元的直接成本，其中33%来自国家 癌症研究所）。创业板计划成员积极使用MCC共享资源设施，因为最初 2013年癌症中心资助。成员发表了164篇手稿（2013年至2017年），其中 其中72个（44%）是跨方案的，36个（22%）是方案内的，99个（60%）是机构间的。 该项目由2名具有互补的科学和领导专业知识的研究人员共同领导。Dr. John D 'Orazio（专注于DNA修复的医生科学家）和Peter Zhou博士（表观遗传学专家， 上皮-间质传递的代谢重编程）汇集了遗传学方面的专业知识， 不稳定性和癌症（D 'Orazio，主题1），表观遗传调节和代谢（Zhou，主题2和3）。在 除了他们的科学领导作用，每个提供临床翻译，初级教师显着优势， MCC项目之间的指导、沟通，以及MCC流域内人口的专业知识 区

PROJECT SUMMARY/ABSTRACT The Genomic Instability, Epigenetics and Metabolism (GEM) Research Program represents a restructuring and programmatic expansion of the former Redox Injury and Repair (RR) Research Program to reflect burgeoning research strengths of participating members with expertise in highly complementary research thrusts. GEM research efforts are central to the overall Markey Cancer Center (MCC) mission to decrease the burden of cancer in Kentucky, surrounding communities and the nation. GEM investigators determine genetic, epigenetic and metabolic mechanisms that promote cancer development, fuel tumor progression and contribute to therapeutic resistance. The overall goal of this program is to gain a comprehensive understanding of the basic mechanisms of these processes to facilitate development of novel and rational approaches for cancer prevention and therapy. To achieve this goal, GEM has established 3 inter-related themes: 1) research into genomic instability and DNA repair will identify how innate DNA repair pathways interact with environmental mutagens to impact carcinogenesis; 2) research on epigenetic mechanisms of malignancy will delineate how alterations in the epigenome and gene transcription influence carcinogenesis; and 3) research on cancer metabolic reprogramming will decipher the role of metabolic processes that contribute to cancer development with a focus on mitochondrial function and redox-mediated dysregulations. The themes are conceptually linked and feature robust faculty collaboration. GEM program members are pioneers and experts in redox biology, DNA repair, epigenetic regulation and cancer metabolism. The program consists of 18 members from 6 departments in the Colleges of Medicine and Arts and Sciences. The program's cancer- related funding is over $4.9M total annual funding ($3.3M direct costs, of which 33% is from the National Cancer Institute). GEM program members have actively used MCC Shared Resource Facilities since initial Cancer Center Support Grant funding in 2013. Members have published 164 manuscripts (2013 to 2017), of which 72 (44%) are inter-programmatic, 36 (22%) are intra-programmatic, and 99 (60%) are inter-institutional. The program is co-led by 2 researchers with complementary scientific and leadership expertise. Dr. John D'Orazio (a physician scientist focusing on DNA repair) and Dr. Peter Zhou (a specialist in epigenetic and metabolic reprogramming of epithelial-mesenchymal transmission) bring together expertise in genetic instability and cancer (D'Orazio, Theme 1), epigenetic regulation, and metabolism (Zhou, Themes 2 and 3). In addition to their scientific leadership roles, each offers significant strengths in clinical translation, junior faculty mentoring, communications among MCC programs, and expertise on populations within the MCC catchment area.