Center for Circadian Rhythms and Alcohol-Induced Tissue Damage

昼夜节律和酒精引起的组织损伤中心

• 批准号: 10643983
• 负责人: ALI KESHAVARZIAN
• 金额: $ 41.94万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10643983
• 关键词: ARNTL gene; Adult; Alcohol consumption; Alcohols; Blood; Bone Marrow; Brain; Chronic; Chronotherapy; Circadian Dysregulation; Circadian Rhythms; Circadian gene expression; Communities; Consultations; Darkness; Data; Data Analyses; Diet; Disease; Eating; Electronic Mail; Fatty acid glycerol esters; Fee-for-Service Plans; Food; Genetic; Heart; Homeostasis; Housing; Human; Human Resources; Individual; Infrastructure; International; Intervention; Intestines; Jet Lag Syndrome; Kidney; Knock-out; Knockout Mice; Laboratories; Light; Liver; Luciferases; Lung; Melatonin; Methods; Modeling; Molecular; Monitor; Mus; National Institute on Alcohol Abuse and Alcoholism; Organ; Organ failure; Organoids; Outcome; Pancreas; Pathology; Peripheral; Peripheral Blood Mononuclear Cell; Phase; Predisposing Factor; Predisposition; Protocols documentation; R24; Reporter; Reproducibility; Research; Research Design; Research Personnel; Resources; Rodent; Sampling; Schedule; Serum; Services; Sleep; Specimen; Spleen; Standardization; Statistical Data Interpretation; Telephone; Testing; Testis; Time; Tissues; Training; United States; Urine; Water; Wild Type Mouse; Wrist; actigraphy; alcohol involvement; alcohol research; alcohol use disorder; analytical tool; biobank; bone; circadian; circadian pacemaker; clinically significant; cost; innovation; interest; mutant; novel; prevent; problem drinker; programs; shift work; skills; sobriety; social; webinar

ABSTRACT Only a subset of individuals with an alcohol-use disorder develop clinically significant organ damage (~10- 30%) but it is not known what factors predispose individuals to develop clinically significant organ pathology? There is compelling evidence to support the hypothesis that disruption of circadian homeostasis (e.g., shift work, social jet lag) is a plausible susceptibility factor for vulnerability to alcohol-induced pathologies. Interest in the study of circadian rhythms is growing; however, an obstacle to study the interactions between circadian rhythms and alcohol-induced organ damage has been the lack of a combined circadian rhythm and alcohol expertise that is required to conduct these studies as well as the high cost associated with establishing the infrastructure necessary to perform circadian research. The objective of this R24 Alcohol Research Resource Program is to overcome these obstacles by providing the necessary infrastructure, support, and expertise that will allow both alcohol researchers in the United States and internationally to incorporate the study of circadian rhythms into their existing research programs. In order to achieve this objective we propose the following Specific Aims: Aim 1. Provide the essential resources to conduct novel, innovative studies involving alcohol and circadian rhythms. The proposed infrastructure, expertise and personnel in our R24 Program will allow alcohol researchers to investigate innovative hypotheses by conducting studies in our facility. At the conclusion of each study, investigators will be provided with biospecimens from their study to evaluate study-specific outcomes. Aim 2. To provide biospecimens from alcohol-fed, circadian disrupted mice and circadian disrupted humans consuming alcohol. Our R24 Alcohol Research Resource Program will provide biospecimens (from our biorepository) to alcohol researchers to investigate hypotheses using standardized experimental manipulations and assessments. The biospecimens will be from studies that have already been conducted and those that are available for request including both human and mouse specimens. Aim 3. Provide consultation and analytic tools for circadian rhythm research. Our R24 Alcohol Research Resource Program will be a resource for the alcohol research community by providing consultation and training in circadian rhythms research (Aim 3a) and by conducting circadian-specific analyses of data collected in other laboratories (Aim 3b). The resources of this NIAAA R24 Alcohol Research Resource Program will facilitate scientific rigor and reproducibility across labs in alcohol and circadian rhythm experimentation. These efforts are expected to lead to a significantly greater understanding of the overlapping or dissimilar disease mechanisms in each organ which should lead to identification of novel targets and interventions to prevent and treat alcohol-induced organ damage.

抽象的 只有一部分患有酒精使用障碍的个体会出现临床上显着的器官损伤（~10- 30%），但尚不清楚哪些因素容易导致个体出现具有临床意义的器官病理学？ 有令人信服的证据支持这样的假设：昼夜节律稳态被破坏（例如，改变 工作、社交时差）可能是酒精诱发疾病的一个易感因素。感兴趣 对昼夜节律的研究正在不断发展；然而，研究昼夜节律之间的相互作用是一个障碍 节律和酒精引起的器官损伤是由于缺乏昼夜节律和酒精的结合 进行这些研究所需的专业知识以及建立这些研究所需的高成本 进行昼夜节律研究所需的基础设施。 R24 酒精研究资源的目标 该计划旨在通过提供必要的基础设施、支持和专业知识来克服这些障碍 将允许美国和国际上的酒精研究人员将昼夜节律的研究纳入其中 节奏融入他们现有的研究计划。为了实现这一目标，我们提出以下建议 具体目标： 目标 1. 提供必要的资源来开展涉及酒精的新颖、创新的研究 和昼夜节律。我们的 R24 计划中拟议的基础设施、专业知识和人员将允许 酒精研究人员通过在我们的设施中进行研究来调查创新假设。结论时 在每项研究中，研究人员都将获得其研究中的生物样本，以评估特定研究 结果。目标 2. 提供来自酒精喂养、昼夜节律紊乱的小鼠和昼夜节律紊乱的生物样本 人类饮酒。我们的 R24 酒精研究资源计划将提供生物样本（来自 我们的生物储存库）让酒精研究人员使用标准化实验来研究假设 操纵和评估。生物样本将来自已经进行的研究 可供索取的样本包括人类和小鼠样本。目标 3. 提供咨询 以及昼夜节律研究的分析工具。我们的 R24 酒精研究资源计划将是 通过提供昼夜节律方面的咨询和培训，为酒精研究界提供资源 研究（目标 3a）并对其他实验室收集的数据进行特定昼夜节律分析（目标 3b). NIAAA R24 酒精研究资源计划的资源将促进科学严谨性和 酒精和昼夜节律实验中跨实验室的可重复性。这些努力预计将导致 更好地了解每个器官重叠或不同的疾病机制 这应该导致确定新的目标和干预措施来预防和治疗酒精诱发的器官 损害。

项目成果

Colonic Epithelial Circadian Disruption Worsens Dextran Sulfate Sodium-Induced Colitis.

• DOI: 10.1093/ibd/izac219
• 发表时间: 2023-03-01
• 期刊: INFLAMMATORY BOWEL DISEASES
• 影响因子: 4.9
• 作者: Jochum, Sarah B.;Engen, Phillip A.;Shaikh, Maliha;Naqib, Ankur;Wilber, Sherry;Raeisi, Shohreh;Zhang, Lijuan;Song, Shiwen;Sanzo, Gabriella;Chouhan, Vijit;Ko, Frank;Post, Zoe;Tran, Laura;Ramirez, Vivian;Green, Stefan J.;Khazaie, Khashayarsha;Hayden, Dana M.;Brown, Mark J.;Voigt, Robin M.;Forsyth, Christopher B.;Keshavarzian, Ali;Swanson, Garth R.
• 通讯作者: Swanson, Garth R.

Disrupted diurnal oscillation of gut-derived Short chain fatty acids in shift workers drinking alcohol: Possible mechanism for loss of resiliency of intestinal barrier in disrupted circadian host.

• DOI: 10.1016/j.trsl.2020.04.004
• 发表时间: 2020-07
• 期刊: Translational research : the journal of laboratory and clinical medicine
• 作者: Swanson GR;Siskin J;Gorenz A;Shaikh M;Raeisi S;Fogg L;Forsyth C;Keshavarzian A
• 通讯作者: Keshavarzian A