Clinical Resource for Alcoholic Hepatitis Inestigation

项目摘要 酒精性肝炎（AH）是酒精性肝病（ALD）的急性表现，通常伴有 严重的预后尽管皮质类固醇治疗对短期生存有积极作用， 这种治疗并不理想，大约一半的患者在短时间内仍然死亡。一 在急性AH的研究中，主要未满足的需求是缺乏一种可靠的动物模型， 所有的人类疾病。因为基于人类的转化研究 样本在理解酒精性肝炎的机制中起着关键作用， 来自严重AH患者的生物标本的收集可以大大有助于设计新的 治疗策略约翰霍普金斯医院急性AH的肝移植（LT）项目提供了 这是一个独特的机会，我们可以创建一个临床资源， 社区和方便访问，否则无法获得标本。在这个支持下， 我们已经建立了一个收集人体样本的中心设施。的可用性 大量的肝组织和不同的肝细胞类型从严重的AH患者到酒精 研究界已经产生了一个创新的资源，急性AH的转化研究。 在上一个资助期内，我们从30多名调查员中， 在各机构/大学发表了18篇论文，在著名期刊上发表。R24的目标是 赠款更新是继续开发严重AH研究的临床资源， 继续满足调查人员当前和日益增长的需求，并慷慨地提供我们的资源 向整个酒精研究界具体来说，我们需要制造更多的人体组织 （来自严重AH和其他肝病患者的肝脏）可用于任何 调查人员要求这些。此外，我们还将在约翰霍普金斯大学提供专业知识， 来自严重AH的单细胞转录组和蛋白质组数据库， 研究社区和超越。具体目标将包括维持一个集中设施， 从患有严重AH和其他肝病的患者中收集人类样本， 向任何有需要的研究者提供我们的临床资源，产生单细胞RNA， 测序（scRNA-seq）数据集和蛋白质组学和蛋白质翻译后修饰 (PTM)严重AH或酒精性肝硬化（AC）患者的病变肝脏数据集， 使其可用于酒精研究界的数据挖掘/假设生成。 我们将继续通过分享我们独特的临床资源来促进合作。

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.