Core 1: Pre-clinical Modeling Core

核心 1：临床前建模核心

• 批准号: 10005123
• 负责人: Nicole Leanne Ward
• 金额: $ 31.62万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-20 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10005123
• 关键词: Acute; Animal Model; Animals; Back; Big Data; Bioinformatics; Biological Markers; Biological Models; Blood; Blood Cells; Bone Marrow Transplantation; Cells; Clinical; Core Facility; Data; Data Analyses; Engineering; Future; Gene Proteins; Generations; Genetic; Germ-Free; Gnotobiotic; Goals; Human; Imiquimod; Immune response; In Vitro; Inflammation; Inflammatory; Knock-out; Knockout Mice; Link; Mediating; Mediator of activation protein; Methodology; Modeling; Modification; Molecular; Molecular Genetics; Mouse Strains; Mus; Pathogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Pre-Clinical Model; Preclinical Testing; Psoriasis; Research; Research Project Grants; Resources; Role; Sampling; Skin; Structure; System; Technology; Testing; Tissues; Transgenic Organisms; Translating; Translational Research; Transplantation; Validation; Xenograft procedure; bacteriome; base; clinical application; clinical care; clinical translation; cohort; comorbidity; drug testing; efficacy testing; experimental study; flexibility; genetic approach; genetic manipulation; in vivo; innovation; insight; interleukin-17C; interleukin-23; meetings; metabolomics; microbial; mouse model; mycobiome; novel; pre-clinical; preclinical evaluation; reconstitution; skin lesion; skin xenograft; success; tool; transcriptomics; treatment response

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.

Cort临床前建模核心（PMC）将作为协作研究的资源 项目（CRP），提供启用技术和模型系统，用于专门测试目标 由应用的元论核心（AMC）确定。 CWRU Cort的广泛目标是结合新的目标 采用高级鼠和人类实验方法的生物信息学方法来翻译 科学发现中的临床应用，更灵活地针对牛皮癣和相关的疗法 炎症合并症。这个目标需要一系列可容易且灵活/适应性 牛皮癣与体内系统相关且创新的体内系统，可以测试广泛的新颖概念， 特定的介体/途径，以及特定重新利用和抗疾病药物的有效性。 PMC将见面 通过与AMC和CRP紧密合作以提供所有必需的转基因和牛皮癣的小鼠，这种需求 模型和孤立的组织，血液和细胞用于分析以及生物信息学衍生的生物标志物和靶标 一代。 PMC将通过产生的假设的CRP产生和测试 人和老鼠生物信息学数据。 PMC的目标包括提供启用材料，技术 牛皮癣小鼠模型和小鼠分子遗传学方面的专业知识，这些遗传学将允许并增强成功 CRP的目的和目标的完成。为了支持CRP的目标，PMC将：A。提供 牛皮癣状皮肤注射的转基因小鼠模型； B.工程师新创新 基于AMC鉴定的新基因/蛋白质的遗传小鼠模型； C.提供原代细胞 从遗传操纵的小鼠中分离出来进行体内假设检测； D.确定最合适的 牛皮癣小鼠模型测试AMC鉴定的途径特异性药物的效率，并生成和 向CRP提供小鼠进行临床前测试和评估；和E.产生无菌小鼠并重新 引入AMC鉴定的细菌/真菌组物种，并向CRP提供动物以进行分析 和假设检验。 PMC还将为其他“ OMICS”数据提供重新的数据生成 通过新型途径，生物标志物，微/真菌组和细胞的AMC进行分析和鉴定 介体，促进牛皮癣发病机理的新见解，从而在临床牛皮癣患者中验证 样品。 PMC提供了一个协调的卓越中心，从而创建了新的 现有的牛皮癣动物模型，以更好地检验细胞和分子机制 介导牛皮癣。在高度互动核的新型Cort结构中，与 中央CRP，PMC团队的专业知识，创新和广泛的资源将推动Cort的 改变牛皮癣的理解和临床护理的影响和可持续影响。