Core 1: Pre-clinical Modeling Core

CORT临床前建模核心(PMC)将作为协作研究的资源 项目(CRP)，提供将用于具体测试目标的使能技术和模型系统 由应用Meta-Omics核心(AMC)确定。CWRU CORT的广泛目标是将新的 生物信息学方法与先进的小鼠和人类实验方法来翻译 更灵活地推进银屑病及相关疾病治疗的临床应用的科学发现 炎症性并存。这一目标需要丰富的、易于部署、灵活/适应性强的 牛皮癣-相关和创新的体内系统，允许测试广泛的新概念，作用 特定的介体/途径，以及特定的再利用药物和抗银屑病药物的疗效。PMC将召开会议 这需要通过与AMC和CRP密切合作，提供所有需要的转基因和牛皮癣样小鼠 用于分析的模型和分离的组织、血液和细胞以及生物信息学衍生的生物标志物和靶标 一代。PMC将使CRP能够生成和测试由于以下原因而生成的假设 人类和小鼠生物信息学数据。私营部门委员会的目标包括提供有利的材料、技术 和在牛皮癣小鼠模型和小鼠分子遗传学方面的专业知识，将允许和加强成功 完成CRP的目的和目的。为支持《战略规划》的目标，项目管理委员会将：a.提供 基因改造现有的牛皮癣样皮炎小鼠模型；B.设计新的创新产品 基于AMC鉴定的新基因/蛋白的遗传小鼠模型；C.提供原代细胞 从基因操纵的小鼠中分离出来，用于体外假说测试；D.确定最合适的 银屑病小鼠模型(S)，以测试AMC确定的途径特异性药物的疗效，并产生和 将小鼠提供给CRP进行临床前测试和评估；以及E.产生无菌小鼠并重新建立 介绍AMC鉴定的细菌组/真菌组物种，并将动物提供给CRP进行分析 和假设检验。项目管理委员会还将为其他“组学”数据提供重复数据生成 用AMC分析和鉴定新的途径、生物标志物、微生物/真菌组物种和细胞 介体，为牛皮癣发病机制提供新的见解，使临床牛皮癣患者能够得到验证 样本。PMC提供了一个协调的卓越中心，能够创建新的 现有的牛皮癣动物模型，以更好地测试假设的细胞和分子机制 中间型牛皮癣。在高度交互的核心的新型CORT结构内协同地与 中央CRP、PMC团队的专业知识、创新和广泛的资源将推动CORT 转变和可持续影响牛皮癣的认识和临床护理。

The CORT Preclinical Modeling Core (PMC) will serve as a resource for the Collaborative Research Project (CRP), providing enabling technology and model systems that will be used to specifically test targets identified by the Applied Meta-Omics Core (AMC). The broad goal of the CWRU 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. This goal requires a rich array of readily-deployable and flexible/adaptable psoriasis-relevant and innovative in vivo systems that permit testing of a wide range of novel concepts, roles of specific mediator/pathways, and efficacies of specific repurposed and anti-psoriasis drugs. The PMC will meet this need, by working closely with the AMC and CRP to provide all needed transgenic and psoriasiform mouse models and isolated tissues, blood and cells for analyses and bioinformatic-derived biomarker and target generation. The PMC will enable generation and testing by the CRP of hypotheses generated as a result of human and mouse bioinformatics data. The goals of the PMC include providing enabling materials, technology and expertise in psoriasis mouse models and mouse molecular genetics that will allow and enhance successful completion of the CRP Aims and Objectives. To support the CRP’s objectives, the PMC will: A. Provide genetically modified existing mouse models of psoriasiform skin inflammation; B. Engineer new innovative genetic mouse models based upon novel genes/proteins identified by the AMC; C. Provide primary cells isolated from genetically manipulated mice for ex vivo hypothesis testing; D. Identify the most appropriate psoriasis mouse model(s) to test efficacy of pathway-specific drugs identified by the AMC, and generate and provide mice to the CRP for preclinical testing and evaluation; and E. Generate germ-free mice and re- introduce bacteriome/mycobiome species identified by the AMC and provide animals to the CRP for analysis and hypothesis testing. The PMC will also provide reiterative data generation for additional “omics” data analyses and identification by the AMC of novel pathways, biomarkers, micro/mycobiome species, and cellular mediators, contributing new insight into psoriasis pathogenesis, enabling validation in clinical psoriasis patient samples. The PMC provides a coordinated center of excellence enabling the creation of new, and utilization of existing, animal models of psoriasis to better test the cellular and molecular mechanisms hypothesized to mediate psoriasis. Within the novel CORT structure of highly interactive Cores synergistically interacting with the central CRP, the PMC team's expertise, innovation and extensive resources will drive the CORT's transforming and sustainable impact on psoriasis understanding and clinical care.