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

基本信息

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
项目类别：
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

项目摘要

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，表观遗传学和代谢（GEM）研究计划代表了重组以及以前的氧化还原损伤和维修（RR）研究计划的程序扩展以反映在高度互补研究方面具有专业知识的参与成员的研究优势推力。 GEM研究工作是整个Markey癌症中心（MCC）任务的核心肯塔基州，周围社区和国家的癌症负担。宝石研究人员确定遗传，促进癌症发展，燃料肿瘤进展和的表观遗传和代谢机制有助于治疗性抗性。该计划的总体目标是获得全面的理解这些过程的基本机制，以促进开发新颖和理性的方法预防癌症和治疗。为了实现这一目标，GEM建立了3个相互关联的主题：1）研究进入基因组不稳定性和DNA修复将确定先天DNA修复途径如何与环境诱变者会影响癌变； 2）关于恶性表观遗传机制的研究描述表观基因组和基因转录的改变如何影响癌变； 3）研究关于癌症代谢重编程将破译有助于癌症的代谢过程的作用开发的重点是线粒体功能和氧化还原介导的失调。主题是从概念上链接并具有强大的教师合作。宝石计划成员是先驱者和专家在氧化还原生物学，DNA修复，表观遗传调节和癌症代谢中。该计划包括18个来自医学，艺术与科学学院的6个系的成员。该计划的癌症 - 相关资金超过490万美元的年度资金（330万美元的直接费用，其中33％来自国家癌症研究所）。自初始癌症中心支持赠款资金于2013年。成员已发表了164份手稿（2013年至2017年）， 72（44％）是截面间的，36（22％）是策略内的，而99（60％）是机构间的。该计划由2位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修复的医师科学家）和Peter Zhou博士（表观遗传学和上皮 - 间质传播的代谢重编程）将遗传学的专业知识汇总在一起不稳定性和癌症（D'Orazio，主题1），表观遗传调节和代谢（Zhou，主题2和3）。在除了其科学领导角色外，每个人都在临床翻译中提供了重要的优势指导，MCC计划之间的沟通以及MCC集水区内人口的专业知识区域。