Core 1: Pre-clinical Modeling Core

核心 1：临床前建模核心

• 批准号: 10259874
• 负责人: Nicole Leanne Ward
• 金额: $ 31.41万
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10259874
• 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 repurposing; 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）将作为合作研究的资源 项目（CRP），提供将用于专门测试目标的使能技术和模型系统 应用元组学核心（AMC）CWRU CORT的广泛目标是将联合收割机 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，更灵活地推进银屑病及相关疾病的治疗 炎性合并症。这一目标需要一系列丰富的可随时部署和灵活/适应性强的 银屑病相关的和创新的体内系统，允许测试广泛的新概念， 特定的介质/途径，以及特定的再利用和抗银屑病药物的功效。PMC将与 这种需要，通过与AMC和CRP密切合作，提供所有需要的转基因和银屑病样小鼠， 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能够生成和检验由于以下原因而生成的假设： 人类和小鼠生物信息学数据。PMC的目标包括提供使能材料、技术 以及银屑病小鼠模型和小鼠分子遗传学方面的专业知识， 完成CRP的宗旨和目标。为了支持CRP的目标，PMC将：提供 遗传修饰的银屑病样皮肤炎症的现有小鼠模型; B.设计新的创新 基于AMC鉴定的新基因/蛋白质的遗传小鼠模型; C.提供原电池 分离自遗传操作的小鼠用于离体假设检验; D.确定最合适的 银肩病小鼠模型以测试AMC鉴定的途径特异性药物的功效，并产生和 向CRP提供小鼠用于临床前测试和评估;以及E.生成无菌小鼠并重新- 引入AMC鉴定的细菌组/分枝杆菌组物种，并将动物提供给CRP进行分析 和假设检验。PMC还将为额外的“组学”数据提供迭代数据生成 通过AMC分析和鉴定新的途径、生物标志物、微生物/真菌生物群物种和细胞 介质，为银屑病发病机制提供新的见解，使临床银屑病患者的验证成为可能 样品PMC提供了一个协调的卓越中心，能够创建新的，并利用 现有的银屑病动物模型，以更好地测试假设的细胞和分子机制， 介导银屑病。在高度相互作用的核心的新型CORT结构中， 中央CRP，PMC团队的专业知识，创新和广泛的资源将推动CORT的 改变和持续影响银屑病的认识和临床护理。