Psoriasis Center of Research Translation

凯斯西储大学（CORT）翻译研究中心将继续推进 使用尖端的系统生物学方法， 将以患者为中心的数据整合到丰富的协同/协作机构环境中。我们将 利用我们的专业知识和经验，利用广泛的临床前、临床和翻译资源， CWRU跨学科研究团队，其中包括生物信息学，微/myocobiome，牛皮癣 患者护理、皮肤免疫学和转基因模型。 CORT的总体目标是将联合收割机新的生物信息学方法与先进的小鼠和 人类实验方法将科学发现转化为临床应用， 银屑病和相关炎症合并症的先进疗法。我们高度创新、协同和 跨学科CORT模型将使用合作研究项目（CRP）作为中心枢纽， 来自2个高度互动的研究核心的定向输入，以完善和测试假设，识别和测试 药物引导和对银屑病和相关炎症合并症的进一步了解。为此，CRP 将整合来自以下方面的输入：1）临床前建模核心（PMC），该核心将提供并定制我们的许多 经验证的、独特的转基因银屑病样动物模型和可转化的人类异种移植方法， 对于翻译新的介体/途径作用和药物先导物至关重要; 2）应用Meta-组学核心（AMC）， 这将对个体患者应用多平台（转录组、代谢组、微生物/真菌生物组）生物信息学 和鼠样品来鉴定新的途径特异性靶点。对这些目标进行迭代实验测试 PMC和CRP的反馈将确定银屑病发病机制的关键新途径， 从新药干预或将现有药物用于银屑病治疗中获益。 我们以患者为中心的翻译方法将开发和增强一种新颖，全面和高度 约850例银屑病/银屑病关节炎单例患者病例记录的注释数据库， 来自CLEARPATH（一个基于俄亥俄州医疗供应商联盟的统一EMR存储库， 研究访问），与炎症标志物分层的子集。每个病人的电子病历，我们会直接 整合AMC与CRP合作创建的他/她的Meta组学数据，以创建一个“组学集成 EMR（EMRi）数据集。这些有凝聚力的多平台个人数据记录将识别牛皮癣患者 基于从其“Meta'Omics”分析鉴定的独特扰动的内型。我们的总体 假设是，通过有力地结合现有的和发展中的银屑病基础科学数据集， 记录，生物信息学和计算系统生物学与双向小鼠和人类研究，我们 将确定新的治疗靶点和重新利用的药物，这些药物可以迅速进入临床试验， 改善牛皮癣治疗和患者护理。

The Psoriasis Center of Research Translation at Case Western Reserve University (CORT) will advance translational discovery and application in psoriasis using a cutting-edge systems biology approach that integrates patient-centered data within a rich and synergistic /collaborative institutional environment. We will leverage extensive preclinical, clinical and translational resources with the expertise and experience of our CWRU interdisciplinary research team, which encompasses bioinformatics, micro/myocobiome, psoriasis patient care, cutaneous immunology and transgenic models. The overall goal of the CORT is to combine new bioinformatic methodologies with advanced murine and human experimental approaches to translate scientific findings into clinical applications that more nimbly advance therapy for psoriasis and related inflammatory comorbidities. Our highly innovative, synergistic and cross-disciplinary CORT model will use a collaborative research project (CRP) as a central hub with bi- directional input from 2 highly interactive research cores, to refine and test hypotheses, identify and test drug leads and advance understanding of psoriasis and related inflammatory comorbidities. To do so, the CRP will integrate input from the: 1) Preclinical Modeling Core (PMC), that will provide and customize our many validated, unique transgenic psoriasiform animal models and translatable human xenograft approaches, essential to translating new mediator/pathway roles and drug leads; 2) Applied Meta-`Omics Core (AMC), that will apply multi-platform (transcriptome, metabolome, micro/mycobiome) bioinformatics to individual patient and murine samples to identify novel pathway-specific targets. Iterative experimental testing of these targets and feedback from the PMC and CRP will identify key novel pathways critical for psoriasis pathogenesis likely to benefit from intervention by new drugs or repurposed existing drugs for psoriasis therapy. Our patient-centered translational approach will exploit and enhance a novel, comprehensive and highly annotated database of ~850 psoriasis/psoriatic arthritis single-patient case records that combines clinical information derived from CLEARPATH (an Ohio medical provider consortium-based unified EMR repository for research access), with inflammation markers that stratify subsets. Into each patient's EMR, we will directly integrate his/her meta'Omics data created by the AMC working with the CRP, to create an 'Omics-integrated EMR (EMRi) data set. These cohesive multi-platform personal data records will identify psoriasis patient endotypes based upon unique perturbations identified from their “meta'Omics” analyses. Our overarching hypothesis is that by powerfully combining existing and developing psoriasis basic science datasets, patient records, bioinformatics and computational systems biology with bi-directional mouse and human studies, we will identify new therapeutic targets and repurposed drugs that can be expeditiously moved to clinical trials, improving psoriasis treatment and patient care.