Environmental Liver Disease

环境性肝病

• 批准号: 9762903
• 负责人: Matthew C Cave
• 金额: $ 51.72万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9762903
• 关键词: Academia; Address; Adolescent; Adult; Affect; Animal Model; Area; Cardiovascular Diseases; Cessation of life; Chemical Exposure; Chemicals; Child; Cirrhosis; Collaborations; Data; Development; Diabetes Mellitus; Endocrine; Environment; Environmental Health; Epidemiologist; Exposure to; Fatty Liver; Goals; Government Agencies; Health; Hepatocyte; Industry; Lipids; Liver; Liver diseases; Malignant neoplasm of liver; Medical Societies; Metabolism; Methods; Mission; National Institute of Environmental Health Sciences; Nutrient; Obesity; Physicians; Poison; Policies; Polychlorinated Biphenyls; Population; Practice Guidelines; Reproducibility; Research; Resources; Scientist; Strategic Planning; Time; Training and Education; Transplantation; Vinyl Chloride; Vision; Work; chronic liver disease; diagnostic biomarker; disease registry; environmental chemical; global health; human subject; innovation; next generation; programs; sex

Liver disease is a major global health problem. Fatty liver disease, or excess accumulation of lipids in hepatocytes, affects more than 25% of the worldwide adult population, but children and adolescents may also be affected. Chronic liver disease may progress to cirrhosis and liver cancer resulting in liver-related death or transplantation. Liver disease also impacts the development of diabetes and cardiovascular disease. Liver diseases may be caused or influenced by exposures to environmental chemicals, but this is an understudied area. To address these problems, this project establishes a major integrative and collaborative research program, the Environmental Liver Disease Revolutionizing Innovative, Visionary Environmental Health Research Program (ELD-RIVER). ELD-RIVER will have a transformative impact in the field. The project investigates two broad scientific themes: (i) the impact of endocrine and metabolism disrupting chemicals (EDCs/MDCs) in fatty liver disease, and (ii) other liver diseases (such as liver cancer) associated with chemical exposures. The ELD-RIVER takes a broad integrative scientific approach by investigating relevant chemicals; nutrient:chemical interactions; both animal models and human subjects; and both sexes through state-of-the-art methods including multi-‘omics. EDC/MDC exposures may also impact liver disease through their effects on obesity and diabetes. Thus, obesity and diabetes endpoints will also be evaluated. While the specific projects are expected to evolve over time, the initial work focusses on exposures to polychlorinated biphenyls and vinyl chloride. Both of these chemicals currently rank in the top five in the Agency for Toxic Substances and Disease Registry (ATSDR) Substance Priority List. ELD-RIVER strictly adheres to the principles of scientific rigor and reproducibility and data transparency and availability. ELD-RIVER leverages existing collaborations between multiple organizations including academia, government agencies, industry, and scientific/medical societies. The vision is for ELD-RIVER to become the global hub for environmental liver disease research. To accomplish its translational mission, the program integrates the work of basic scientists, epidemiologists, and physicians. The project will also develop diagnostic biomarkers, new treatments, practice guidelines, and it has the potential to impact policy change. Along the way, unique institutional education/training resources will be utilized so that ELD-RIVER will help produce the next generation of environmental health scientists. The work proposed is relevant to Strategic Plan of the National Institute of Environmental Health Sciences (Themes 1, 2, and 5 and Goals 1, 4, 7, and 8).

肝病是一个主要的全球健康问题。脂肪肝疾病，或脂质过度积累， 肝细胞，影响超过25%的全球成人人口，但儿童和青少年也可能 受到影响。慢性肝病可能进展为肝硬化和肝癌，导致肝脏相关死亡或 移植肝脏疾病也影响糖尿病和心血管疾病的发展。肝 疾病可能是由接触环境化学物质引起或影响的，但这一点尚未得到充分研究 区为了解决这些问题，本项目建立了一个主要的综合和合作研究 环境肝病革命性创新，有远见的环境健康研究 程序（ELD-RIVER）。 ELD-RIVER将在该领域产生变革性影响。该项目调查了两个广泛的科学 主题：（一）内分泌和代谢干扰化学品（EDCs/MDCs）在脂肪肝疾病中的影响， 及（ii）与化学品接触有关的其他肝脏疾病（例如肝癌）。ELD河需要一个 广泛的综合科学方法，通过调查相关化学品;营养素：化学相互作用; 动物模型和人类受试者;以及通过包括多组学在内的最新技术水平的方法对两性进行研究。 EDC/MDC暴露也可能通过其对肥胖和糖尿病的影响而影响肝脏疾病。因此，肥胖症 还将评估糖尿病终点。 虽然具体项目预计将随着时间的推移而发展，但最初的工作重点是 多氯联苯和氯乙烯。这两种化学品目前都在原子能机构中排名前五 有毒物质和疾病登记处（ATSDR）的物质优先列表。ELD-RIVER严格遵守 科学严谨性和可重复性以及数据透明性和可用性的原则。ELD-RIVER利用 包括学术界、政府机构、工业界在内的多个组织之间的现有合作， 科学/医学协会。ELD-RIVER的愿景是成为全球环境肝脏中心 疾病研究。为了完成其转化使命，该计划整合了基础科学家的工作， 流行病学家和医生。该项目还将开发诊断生物标志物，新的治疗方法， 它有可能影响政策的变化。沿着，独特的机构教育/培训 资源将得到利用，以便ELD-RIVER将有助于产生下一代环境健康 科学家拟议的工作与国家环境卫生研究所的战略计划有关 科学（主题1、2和5以及目标1、4、7和8）。