Psoriasis Center of Research Translation

银屑病研究翻译中心

• 批准号: 10005116
• 负责人: Kevin D Cooper
• 金额: $ 131.66万
• 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/10005116
• 关键词: Advisory Committees; Animal Model; Artificial Intelligence; Basic Science; Bioinformatics; Biological; Biological Markers; Biological Models; Blood Cells; Cells; Clinical; Clinical Trials; 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; comorbidity; 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.

凯斯西储大学 (CORT) 银屑病研究翻译中心将推进 使用尖端系统生物学方法在银屑病中进行转化发现和应用 将以患者为中心的数据整合到丰富且协同/协作的机构环境中。我们将 利用广泛的临床前、临床和转化资源以及我们的专业知识和经验 CWRU 跨学科研究团队，涵盖生物信息学、微/肌生物组、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方法与先进的小鼠和 人类实验方法将科学发现更灵活地转化为临床应用 银屑病和相关炎症合并症的先进治疗。我们高度创新、协同和 跨学科 CORT 模型将使用协作研究项目 (CRP) 作为双中心枢纽 来自 2 个高度互动的研究核心的定向输入，以完善和测试假设、识别和测试 药物引导并促进对银屑病和相关炎症合并症的了解。为此，CRP 将整合来自以下方面的输入： 1) 临床前建模核心 (PMC)，它将提供和定制我们的许多 经过验证的、独特的转基因银屑病动物模型和可转化的人类异种移植方法， 对于转化新的介体/途径角色和药物先导化合物至关重要； 2）应用元组学核心（AMC）， 将多平台（转录组、代谢组、微生物组/真菌组）生物信息学应用于个体患者 和小鼠样本来识别新的途径特异性靶标。这些目标的迭代实验测试 来自 PMC 和 CRP 的反馈将确定对银屑病发病机制至关重要的关键新途径 从新药干预或重新利用现有药物治疗牛皮癣中获益。 我们以患者为中心的转化方法将开发和增强一种新颖、全面和高度 包含约 850 个银屑病/银屑病关节炎单患者病例记录的带注释数据库，其中结合了临床 来自 CLEARPATH（俄亥俄州医疗提供者联盟的统一 EMR 存储库）的信息 研究访问），具有对子集进行分层的炎症标记物。进入每个患者的EMR，我们会直接 整合由 AMC 与 CRP 合作创建的他/她的元组学数据，以创建“组学集成” 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“元组学”分析中识别出的独特扰动的内型。我们的首要任务 假设是，通过强有力地结合现有和正在开发的银屑病基础科学数据集，患者 记录、生物信息学和计算系统生物学以及双向小鼠和人类研究，我们 将确定新的治疗靶点和重新利用的药物，这些药物可以迅速转移到临床试验， 改善牛皮癣的治疗和患者护理。