Psoriasis Center of Research Translation

银屑病研究翻译中心

• 批准号: 9792242
• 负责人: Kevin D Cooper
• 金额: $ 130.84万
• 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/9792242
• 关键词: Advisory Committees; Animal Model; Artificial Intelligence; Basic Science; Bioinformatics; Biological; Biological Markers; Biological Models; Blood Cells; Cells; Clinical; Clinical Trials; Comorbidity; Computational Biology; Computational algorithm; Computerized Medical Record; Coupled; Critical Pathways; Custom; Cutaneous; Data; Data Analyses; Data Set; Databases; Decision Making; Development; Drug Targeting; Environment; FDA approved; Feedback; Gene Expression; Gene Targeting; Goals; Growth; Human; Human Resources; Immunology; Inflammatory; Interdisciplinary Study; Intervention; Laboratories; Leadership; Link; Machine Learning; Mediator of activation protein; Medical; Medical center; Methodology; Methods; Microbe; Modeling; Molecular; Mus; Ohio; Pathogenesis; Pathogenicity; Pathway interactions; Patient Care; Patients; Pharmaceutical Preparations; Pre-Clinical Model; Provider; Psoriasis; Psoriatic Arthritis; Records; Records Controls; Research; Research Project Grants; Resource Allocation; Resources; Role; Sampling; Skin; Systems Biology; Techniques; Technology; Testing; Transgenic Model; Transgenic Organisms; Translating; Translational Research; Universities; University Hospitals; Xenograft procedure; base; clinical application; cohesion; cohort; data mining; design; differential expression; drug development; drug discovery; drug testing; effective intervention; experience; improved; individual patient; inflammatory marker; innovation; meetings; metabolome; metabolomics; microbiome; multimodality; mycobiome; new therapeutic target; novel; novel strategies; novel therapeutics; patient oriented; pre-clinical; pre-clinical research; programs; repository; response; synergism; therapeutic target; transcriptome; transcriptomics; translational approach

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.

Case Western Reserve University（Cort）的牛皮癣研究中心将进步 使用尖端的系统生物学方法的牛皮癣的转化发现和应用 在富裕 /协同 /协作的机构环境中集成了以患者为中心的数据。我们将 利用广泛的临床前，临床和翻译资源，并具有我们的专业知识和经验 CWRU跨学科研究团队，其中包括生物信息学，微/肌生物症，牛皮癣 患者护理，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高级鼠结合在一起 人类的实验方法将科学发现转化为更灵活的临床应用 牛皮癣和相关炎症合并症的预先治疗。我们高度创新，协同的和 跨学科CORT模型将使用协作研究项目（CRP）作为BI-的中心枢纽 从2个高度互动研究核心的定向输入，以完善和检验假设，识别和测试 药物引导并提高对牛皮癣和相关炎症合并症的了解。为此，CRP 将从：1）临床前建模核心（PMC）集成输入，该核心将提供并自定义我们的许多 经过验证的独特的转基因牛皮癣动物模型和可翻译的人异种移植方法， 要翻译新的调解人/途径角色和药物铅； 2）应用元元素核心（AMC）， 这将适用多平台（转录组，代谢组，微型/mycobiome）生物信息学 和鼠样品以鉴定新的途径特异性靶标。这些目标的迭代实验测试 PMC和CRP的反馈将确定对牛皮癣发病机理至关重要的关键新型途径 受益于新药的干预或重新定位用于牛皮癣治疗的现有药物。 我们以患者为中心的翻译方法将利用和增强新颖，全面且高度 〜850牛皮癣/银屑病关节炎单患有病例记录的注释数据库，结合了临床 来自ClearPath（俄亥俄州医疗提供商联盟的统一EMR存储库）的信息 研究访问），带有分层子集的炎症标记。进入每个患者的EMR，我们将直接 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。这些有凝聚力的多平台个人数据记录将识别牛皮癣患者 基于从其“元词”分析中确定的独特扰动的内型。我们的总体 假设是，通过有力结合现有和发展的牛皮癣基础科学数据集，患者 带有双向小鼠和人类研究的记录，生物信息学和计算系统生物学，我们 将确定可以迅速转移到临床试验的新的治疗靶标和重新利用的药物， 改善牛皮癣治疗和患者护理。