Psoriasis Center of Research Translation

凯斯西储大学牛皮癣研究翻译中心将推进 利用尖端系统生物学方法在银屑病中的翻译发现和应用 将以患者为中心的数据集成到丰富的协同/协作机构环境中。我们会 利用我们的专业知识和经验，充分利用广泛的临床前、临床和翻译资源 CWRU跨学科研究团队，涵盖生物信息学、微生物/真菌生物组、牛皮癣 病人护理、皮肤免疫学和转基因模型。 CORT的总体目标是将新的生物信息学方法与先进的小鼠和 将科学发现更灵活地转化为临床应用的人体实验方法 牛皮癣及相关炎症性并存的高级治疗。我们的高度创新、协同和 跨学科CORT模型将使用协作研究项目(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 药物引导并促进对牛皮癣和相关炎症性并存的了解。要做到这一点，CRP 将集成来自：1)临床前建模核心(PMC)的输入，该核心将提供和定制我们的 经过验证的、独特的转基因牛皮癣样动物模型和可翻译的人类异种移植方法， 对翻译新的介体/途径作用和药物先导至关重要；2)应用Meta-`Omics Core(AMC)， 这将把多平台(转录组、代谢组、微生物/真菌生物组)生物信息学应用于个体患者 和小鼠样本来识别新的路径特异性靶标。这些靶子的迭代实验测试 来自PMC和CRP的反馈将确定可能对银屑病发病至关重要的关键新途径 从治疗银屑病的新药或改变现有药物用途的干预中受益。 我们以患者为中心的翻译方法将开发和增强新颖、全面和高度 结合临床的约850个牛皮癣/牛皮癣关节炎单患者病例记录的带注释的数据库 来自ClearPath的信息(俄亥俄州医疗提供商联盟的统一EMR存储库，用于 研究访问)，具有分层的子集的炎症标志物。每一位病人的电子病历，我们会直接 整合由AMC与CRP合作创建的他/她的Meta‘Omics数据，以创建’Omics-集成 EMR(EMRI)数据集。这些连贯的多平台个人数据记录将识别牛皮癣患者 内型基于从他们的“Meta‘Omics”分析中识别的独特的扰动。我们最重要的是 假设是，通过将现有的和发展中的牛皮癣基础科学数据集强有力地结合起来，患者 记录，生物信息学和计算系统生物学与双向老鼠和人类研究，我们 将确定新的治疗靶点和重新调整用途的药物，可以迅速转移到临床试验， 改善牛皮癣的治疗和患者护理。

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.