Pathogenesis and Therapy of Ulcerative Colitis - From Sequence to Mechanisms

溃疡性结肠炎的发病机制和治疗——从序列到机制

• 批准号: 418055832
• 负责人: Professor Dr. Christoph Becker
• 金额: --
• 依托单位: Medizinische Klinik 1 - Gastroenterologie, Pneumologie und Endokrinologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/418055832?language=en
• 关键词: Pathogenesis; Therapy; Ulcerative; Colitis; Sequence

Inflammatory bowel disease comprises Crohn's disease and ulcerative colitis and presents a chronic intestinal yet incurable disease group. Although the introduction of novel therapies has improved the overall quality of life, there is still a substantial subgroup with an unsatisfactory disease course. Besides a better understanding of the pathogenesis, unmet needs include the detailed dissection of IBD subtypes, the prediction of the disease course as well as causative and disease-specific therapies. In order to fill this knowledge gap, we are developing within the framework of the newly established Collaborative Research Center project "Immune-Epithelial Communication in Inflammatory Bowel Diseases; IEC in IBD" an integrated platform which merges large scale omic-datasets from IBD patients with corresponding clinical disease status, denoted IBDome. The database will be realized on a platform that is similar to already established platforms for solid cancers, where one of the project contributors was mainly involved in. The data will consist of clinical data and biomedical information derived from comprehensive molecular characterization of collected intestinal tissue, peripheral blood and stool using RNA sequencing, exome sequencing, 16s microbiome sequencing, mass cytometry (cytometry by time of flight; CyTOF), and histopathology. Within the framework of the project we are currently establishing a Crohn's disease cohort for IBDome. However, an ulcerative colitis cohort is currently missing. Aim of this project is to complement IBDome by including an ulcerative colitis cohort with three major aims: i) provide a yet lacking in-depth analysis of ulcerative colitis patients with active and inactive disease, ii) identify mechanisms and pathways discriminating ulcerative colitis from Crohn’s disease and iii) identify predictors of response for three treatment strategies, namely TNF-alpha antibodies, anti-integrin antibodies (vedolizumab) as well as the tyrosine kinase inhibitor tofacitinib. The integrated biomolecular, imaging, and clinical data (disease phenotype, disease activity, medication, complications) and its bioinformatics analyses will be made available through a web-based front-end to all researchers within the project in order to enable further exploration of the data and generation of testable hypotheses. We envision to further developing IBDome to a reference database for IBD during the course of the project, which will be populated with a large number of patient samples analyzed using both, deep and broad profiling. Hence, we will provide a central resource platform not only for the project but also for the scientific community and thereby strengthen translational research and enable novel insights into IBD pathogenesis and ultimately the discovery of novel therapeutic strategies.

炎症性肠病涉及克罗恩氏病和溃疡性结肠炎，并提出了一个慢性肠道但无法治愈的疾病组。尽管新疗法的引入改善了整体生活质量，但仍有一个大量的亚组，疾病病程不令人满意。除了更好地了解发病机理外，未满足的需求还包括IBD亚型的详细解剖，疾病病程的预测以及谨慎和疾病特异性疗法。为了填补这一知识差距，我们正在新成立的合作研究中心项目的框架内开发“炎症性肠病中的免疫上皮交流； IEC在IBD中”一个集成平台，该平台合并了来自IBD患者的大型Omic-Datasets，具有相应的临床疾病状态，表示IBDOME，表示IBDOME。该数据库将在一个平台上实现，该平台与已建立的固体癌症平台相似，其中一个项目贡献者主要参与其中。数据将包括临床数据和生物医学信息，这些信息来自于收集到的肠道组织的全面分子表征，使用RNA测序，Exceencing，Excy of Cyencect，Excy of Cyencing，Excy of Cyence of Cyencing，Excy of Cyence of Cyencing，Excy of Cyence of Cyence of Cyence，cy cy cy，飞行；在该项目的框架内，我们目前正在为ibdome建立一个克罗恩病队列。但是，目前缺少溃疡性胶体炎队列。该项目的目的是通过包括溃疡性胶体炎队列的三个主要目的来补充IBDOME：i）尚未对患有活性和不活跃疾病的溃疡性碰撞性肿瘤患者进行深入分析，ii）ii）识别机制和途径，确定了克罗恩病和III的溃疡性胶炎的机制和途径。抗体（Vedolizumab）以及酪氨酸激酶抑制剂Tofacitinib。将通过基于Web的前端向项目中的所有研究人员提供综合的生物分子，成像和临床数据（疾病表型，疾病活动，药物，并发症）及其生物信息学分析，以便进一步探索可检验的假设的数据和生成。我们设想在项目过程中将IBDOME进一步开发到IBD的参考数据库，并使用大量使用深层和广泛分析分析的患者样本填充。因此，我们将不仅为该项目，而且为科学界提供一个中央资源平台，从而加强转化研究，并为IBD发病机理以及最终发现新颖的治疗策略提供新的见解。