Clinical Resource for Alcoholic Hepatitis Inestigation

酒精性肝炎调查的临床资源

• 批准号: 10652344
• 负责人: ZHAOLI SUN
• 金额: $ 68.59万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10652344
• 关键词: Acute; Acute Alcoholic Hepatitis; Adrenal Cortex Hormones; Alcohol consumption; Alcoholic Hepatitis; Alcoholic Liver Cirrhosis; Alcoholic Liver Diseases; Animal Model; Basic Science; Biopsy; Blood specimen; COVID-19; COVID-19 pandemic; Caring; Cell Separation; Cells; Cholestasis; Cirrhosis; Clinical; Clinical Research; Collaborations; Collection; Communities; Data; Data Set; Databases; Development; Discontinuous Capillary; Disease; Endothelial Cells; Ethanol; Ethanol Metabolism; Fibrosis; Funding; Gastroenterology; Generations; Goals; Grant; Hepatic Stellate Cell; Hepatocellular Damage; Hepatocyte; Hepatology; Human; Infiltration; Inflammation; Institution; Investigation; Journals; Knowledge; Kupffer Cells; Laboratories; Lead; Liver; Liver diseases; Lymphocyte; Maps; Modeling; Molecular; Mouse Strains; Noise; Paper; Paraffin; Pathogenesis; Pathology; Patients; Post-Translational Protein Processing; Preparation; Principal Investigator; Prognosis; Proteome; Proteomics; Publications; Publishing; R24; Research; Research Personnel; Resources; Rodent; Sampling; Serum; Specimen; Supportive care; Therapeutic; Time; Tissues; Translational Research; Universities; alcohol research; cell type; data mining; design; experimental study; feeding; human data; human tissue; innovation; liver inflammation; liver injury; liver transplantation; meetings; mortality; new therapeutic target; nonalcoholic steatohepatitis; novel therapeutic intervention; patient population; programs; single-cell RNA sequencing; transcriptome; transcriptome sequencing; transcriptomics

Project Summary Alcoholic hepatitis (AH) is an acute manifestation of alcoholic liver disease (ALD), often with a grave prognosis. Despite the positive effects of corticosteroid treatment on short-term survival, this treatment is not ideal and approximately half of patients still die after a short time period. A major unmet need in the study of acute AH is the lack of a reliable animal model that mimics the entire spectrum of this disease in humans. Because translational research based on human samples has a key role in the understanding of mechanisms of alcoholic hepatitis, the collection of bio specimens from patients with severe AH could help substantially in the design of new therapeutic strategies. The liver transplant (LT) program for acute AH at Johns Hopkins provided a unique opportunity for us to create a clinical resource that now serves the alcohol research community and facilitates access to otherwise unavailable specimens. With support from this R24 grant, we have created a centralized facility for collecting human samples. The availability of a large amount of liver tissues and different liver cell types from severe AH patients to the alcohol research community has generated an innovative resource for translational research of acute AH. In the last funding period, we have provided our resource to 50 investigators from over 30 institutions/universities resulting in 18 publications in prestigious journals. The goal of this R24 grant renewal is to continue developing clinical resources for severe AH investigations and to continue meeting investigators’ current and increasing needs and liberally provide our resource to the entire alcohol research community. Specifically, we need to make more human tissues (explanted livers from patients with severe AH and other liver diseases) available to any investigators requesting these. In addition, we will provide expertise at Johns Hopkins to generate single-cell transcriptome and proteome databases from severe AH that may serve the alcohol research community and beyond. Specific aims will include maintaining a centralized facility for collecting human samples from patients with severe AH and other liver diseases and continually providing our clinical resources to any investigators requesting them, generating single-cell RNA- sequencing (scRNA-seq) datasets and proteomic and protein post-translational modifications (PTM) datasets from diseased livers in patients with severe AH or alcoholic cirrhosis (AC) and making them available to the alcohol research community for data mining/hypothesis generation. We will continue to promote collaboration through sharing our unique clinical resource.

项目摘要 酒精性肝炎（AH）是酒精性肝病（ALD）的急性表现，通常是 严重的预后。尽管皮质类固醇治疗对短期生存的积极影响，但 这种治疗不是理想的，大约一半的患者在短时间后仍死亡。一个 急性AH研究中的主要未满足需求是缺乏模仿可靠的动物模型 这种疾病在人类中的全部范围。因为基于人类的翻译研究 样品在对酒精性肝炎机制的理解中具有关键作用，该收集 严重AH患者的生物疗法可以大大帮助设计 治疗策略。约翰·霍普金斯（Johns Hopkins）提供的急性AH肝移植（LT）计划 我们创建一个临床资源的独特机会，现在为酒精研究服务 社区并促进访问其他不可用的标本。在此支持 R24 Grant，我们创建了一个集中式设施来收集人类样本。可用性 从严重AH患者到专辑的大量肝组织和不同的肝细胞类型 研究社区为急性AH的翻译研究创新了创新资源。 在最后的资金期间，我们已向30多个调查员提供了资源 机构/大学在著名的期刊上产生了18个出版物。此R24的目标 Grant Renewal将继续开发临床资源以进行严重的AH调查和 继续满足调查人员的当前和不断增长的需求，并自由提供我们的资源 致整个酒精研究界。具体而言，我们需要制造更多的人体组织 （患有严重AH和其他肝病的患者的外观生命）可用于任何 调查人员要求这些。此外，我们将在约翰·霍普金斯（Johns Hopkins）提供专业知识来生成 来自严重AH的单细胞转录组和蛋白质组数据库，可能有助于酒精 研究社区及其他地区。具体目标将包括维护集中设施 从严重AH和其他肝病的患者中收集人类样本，并不断收集 向要求他们提供的任何调查人员提供我们的临床资源，从而产生单细胞RNA- 测序（SCRNA-SEQ）数据集以及蛋白质组学后翻译后修饰 （PTM）严重AH或酒精性肝硬化患者患病的数据集（AC）和 使其可用于酒精研究界的数据挖掘/假设生成。 我们将通过分享我们独特的临床资源来继续促进合作。