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: 10204896
• 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/10204896
• 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.

项目摘要/摘要 基因组不稳定性、表观遗传学和新陈代谢(GEM)研究计划代表着一种重组 和以前的氧化还原损伤和修复(RR)研究方案的方案扩展，以反映 参与成员在高度互补的研究方面的专业知识迅速增长的研究优势 冲刺。GEM研究工作是整个Markey癌症中心(MCC)降低 肯塔基州、周边社区和全国的癌症负担。宝石研究人员确定了基因， 表观遗传和代谢机制，促进癌症发展，推动肿瘤进展和 会导致治疗抵抗。这个项目的总体目标是全面了解 这些进程的基本机制，以促进开发新的和合理的方法 癌症预防和治疗。为了实现这一目标，创业板确立了三个相互关联的主题：1)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 环境诱变剂对癌症发生的影响；2)恶性意志的表观遗传学机制研究 描述表观基因组和基因转录的变化如何影响癌症的发生；以及3)研究 关于癌症代谢重新编程将破译导致癌症的代谢过程的作用 发展，重点是线粒体功能和氧化还原介导的失调。主题是 概念上相互关联，并具有强大的教职员工协作。创业板计划成员是开拓者和专家 氧化还原生物学、DNA修复、表观遗传调控和癌症新陈代谢。该计划由18个项目组成 来自医学院、文理学院6个系的成员。这个项目的癌症- 相关资金每年超过490万美元(330万美元直接成本，其中33%来自国家 癌症研究所)。GEM计划成员从最初开始就积极使用MCC共享资源设施 癌症中心支持2013年的赠款资助。会员已发表164篇稿件(2013至2017年)， 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。 该项目由两名研究人员共同领导，他们拥有互补的科学和领导专业知识。约翰博士 D‘Orazio(专注于DNA修复的内科科学家)和Peter周博士(表观遗传学和 上皮-间充质传递的代谢重新编程)汇集了遗传学方面的专业知识 不稳定与癌症(D‘Orazio，主题1)、表观遗传调控和新陈代谢(周，主题2和3)。在……里面 除了他们的科学领导角色外，每个人都在临床翻译、初级教员方面提供了显著的优势 指导、MCC项目之间的交流以及关于MCC流域内人口的专业知识 区域。