Project 1: Host Immune Response to Chronic Psoriasis Inflammation

CWRU牛皮癣研究翻译中心(CORT)的总体目标是结合新的 生物信息学方法与先进的小鼠和人类实验方法，以转化科学 更灵活地推进银屑病和相关炎症性疾病治疗的临床应用 合并症。我们高度创新、协同和跨学科的CORT将使用协作研究 项目(CRP)作为一个中央枢纽，来自两个高度互动的研究核心的双向输入，以完善和 测试假说，识别和测试改变用途的药物线索，并促进对牛皮癣及其相关疾病的了解 炎症性并存。为此，CRP将整合来自：1)临床前建模核心的输入 (PMC)，它将提供和定制我们许多经过验证的、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，对于翻译新的介体/途径作用和药物先导是必不可少的； 以及2)应用Meta-‘Omics Core(AMC)，它将应用多平台(转录组、代谢组、 微生物/真菌组)生物信息学用于个体患者和小鼠样本以识别新的途径特异性 目标。对这些目标的迭代实验测试以及来自PMC和CRP的反馈将确定新的 银屑病发病机制中可能受益于新药或改变用途的药物干预的途径 将转化为牛皮癣的治疗。我们最重要的假设是，我们可以将现有的和 开发牛皮癣基础科学数据集、患者记录、生物信息学和计算系统 生物学与鼠和人的双向研究，以确定新的治疗靶点和改变药物的用途 这可以迅速转移到临床试验，改善牛皮癣的治疗和患者护理。测试和 完善这一假设，具体目标是：(1)确定银屑病发病机制和 通过分析银屑病患者的EMR数据、组织和血液样本，获得新的银屑病候选药物；(2) 应用临床前评估AMC识别的基因靶点和通路特异性候选药物的疗效 分子遗传性银屑病小鼠模型。C反应蛋白和核心之间的集中交互将 提供增值的研究成果，远远超过给定的核心或特定 项目可以提供。我们新颖、高度集成和协同的CORT设计，由卓越的 我们跨学科翻译调查团队的资源和专业知识，将发挥变革性和 对牛皮癣领域和患者护理的可持续影响。

The overall goal of the CWRU Psoriasis Center of Research Translation (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 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 repurposed 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; and the 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 novel pathways in psoriasis pathogenesis that are likely to benefit from intervention by new or repurposed drugs that will translate to psoriasis therapy. Our overarching hypothesis is that we can powerfully combine existing and developing psoriasis basic science datasets, patient records, bioinformatics and computational systems biology with bi-directional mouse and human studies to identify new therapeutic targets and repurposed drugs that can be expeditiously moved to clinical trials, improving psoriasis treatment and patient care. To test and refine this hypothesis, the Specific Aims are: (1) Identify new pathways central to psoriasis pathogenesis and new psoriasis drug candidates by analyzing psoriasis patients' EMR data, tissue and blood samples and; (2) Evaluate AMC-identified gene targets and efficacy of pathway-specific drug candidates using preclinical molecular genetic psoriasis mouse models. The concentrated interactions between the CRP and Cores will provide value-added research output, far beyond any incremental advances that a given Core or specific project could provide. Our novel, highly integrated and synergistic CORT design, powered by exceptional resources and expertise of our interdisciplinary translational investigative team, will exert a transformative and sustainable impact on the psoriasis field and patient care.