Genomic Instability, Epigenetics and Metabolism Research Program

基因组不稳定性、表观遗传学和代谢研究项目

• 批准号: 10470113
• 负责人: John A D'Orazio
• 金额: $ 3.25万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-08 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10470113
• 关键词: Adenocarcinoma; Affect; Area; Arts; Attention; Automobile Driving; Autophagocytosis; Basic Science; Biology; Cancer Burden; Cancer Center; Cancer Center Support Grant; Cancer Prevention Intervention; Catchment Area; Chromatin; Collaborations; Communication; Communities; Complex; DNA Repair; DNA Repair Pathway; DNA-(apurinic or apyrimidinic site) lyase; DNA-Directed RNA Polymerase; Development; Diagnostic; Direct Costs; Disease; EZH2 gene; Environment; Enzymes; Epigenetic Process; Epithelial; Extramural Activities; Faculty; Fatty-acid synthase; Funding; Future; Gene Expression; Genetic; Genetic Transcription; Genome Stability; Genomic DNA; Genomic Instability; Goals; Growth; Head and Neck Squamous Cell Carcinoma; Histone H3; Homeostasis; Immunotherapy; Impaired cognition; Impairment; In Situ; Intervention; Investigation; Kentucky; Large Intestine Carcinoma; Lead; Leadership; Link; Lysine; Malignant - descriptor; Malignant Neoplasms; Manuscripts; Mediating; Mediator of activation protein; Medicine; Mesenchymal; Metabolic; Metabolism; Mission; Mitochondria; Molecular; Morbidity - disease rate; Mutagenesis; Mutation; National Cancer Institute; Neoplasm Metastasis; Normal Cell; Nucleosomes; Nucleotide Excision Repair; Oncogenic; Oxidation-Reduction; Paracrine Communication; Phenotype; Physicians; Play; Polycomb; Polymerase; Population; Positioning Attribute; Prevention therapy; Preventive; Process; Publications; Publishing; Research; Research Personnel; Research Project Grants; Resource Sharing; Role; Science; Scientist; Signal Pathway; Slice; Snails; Solid Neoplasm; Specialist; Therapeutic; Tissues; Translating; Translational Research; Triad Acrylic Resin; Universities; aerobic glycolysis; base; cancer cell; cancer initiation; cancer prevention; carcinogenesis; cell transformation; chemotherapy; clinical translation; college; environmental agent; environmental mutagens; epigenetic regulation; epigenetic therapy; epigenome; faculty mentor; injury and repair; inter-institutional; interest; melanocyte; member; metabolome; mitochondrial dysfunction; mortality; non-genetic; novel; programs; recruit; targeted treatment; therapy resistant; transmission process; treatment response; tumor; tumor metabolism; tumor progression

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.

项目概要/摘要 基因组不稳定性、表观遗传学和代谢（GEM）研究计划代表了一次重组 以及前氧化还原损伤和修复（RR）研究计划的计划扩展，以反映 具有高度互补研究专业知识的参与成员的研究实力不断增强 推力。 GEM 研究工作对于马基癌症中心 (MCC) 减少癌症的总体使命至关重要 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、促进肿瘤进展和 有助于治疗抵抗。该计划的总体目标是获得全面的了解 这些过程的基本机制，以促进新的和合理的方法的发展 癌症预防和治疗。为了实现这一目标，GEM设立了3个相互关联的主题：1）研究 深入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 环境诱变剂影响致癌； 2）恶性肿瘤的表观遗传机制研究 描述表观基因组和基因转录的改变如何影响致癌作用； 3）研究 癌症代谢重编程将破译代谢过程对癌症的作用 重点关注线粒体功能和氧化还原介导的失调的发育。主题是 在概念上相互联系并具有强大的教师协作能力。 GEM计划成员都是先驱者和专家 氧化还原生物学、DNA 修复、表观遗传调控和癌症代谢。该计划包括 18 成员来自医学学院、艺术与科学学院的6个系。该计划的癌症—— 相关资金每年总资金超过 490 万美元（直接成本 330 万美元，其中 33% 来自国家 癌症研究所）。 GEM 计划成员自最初以来就积极使用 MCC 共享资源设施 2013 年癌症中心支持拨款。成员发表了 164 篇手稿（2013 年至 2017 年），其中 其中 72 个（44%）是计划间的，36 个（22%）是计划内的，99 个（60%）是机构间的。 该项目由两名具有互补科学和领导专业知识的研究人员共同领导。约翰博士 D'Orazio（专注于 DNA 修复的医学科学家）和 Peter Zhou 博士（表观遗传学和 上皮间质传递的代谢重编程）汇集了遗传领域的专业知识 不稳定性和癌症（D'Orazio，主题 1）、表观遗传调控和代谢（Zhou，主题 2 和 3）。在 除了他们的科学领导作用外，每个人都在临床翻译、初级教师方面具有显着的优势 MCC 项目之间的指导、沟通以及 MCC 流域内人群的专业知识 区域。