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Project 1: Host Immune Response to Chronic Psoriasis Inflammation

项目 1：宿主对慢性银屑病炎症的免疫反应

基本信息

批准号：
10005125
负责人：
Nicole Leanne Ward
金额：
$ 33.34万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
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/10005125
关键词：
Advisory Committees Animal Model Artificial Intelligence Basic Science Bioinformatics Blood Blood specimen Cells Chronic Clinical Clinical Research Clinical Trials Complex Critical Pathways Custom Data Data Set Databases Decision Making Development Disease Drug Targeting Feedback Gene Targeting Genes Genetic Goals Growth Healthcare Human Human Resources Immune response Inflammation Inflammatory Intervention Intervention Studies Lead Leadership Machine Learning Mediator of activation protein Medical Methodology Methods Modeling Molecular Genetics Mus Ohio Output Pathogenesis Pathway interactions Patient Care Patients Pharmaceutical Preparations Phenotype Pilot Projects Pre-Clinical Model Provider Psoriasis Psoriatic Arthritis Records Research Research Project Grants Resource Allocation Resources Role Sampling Skin System Systems Biology Testing Therapeutic Tissue Sample Transgenic Organisms Translating Translational Research Xenograft procedure base clinical application cohesion comorbidity data mining design drug candidate drug discovery drug testing improved in silico in vitro Bioassay individual patient inflammatory marker innovation insight meetings metabolome microbiome mouse model mycobiome new therapeutic target novel novel therapeutics patient oriented patient stratification personalized medicine personalized predictions post intervention pre-clinical pre-clinical research programs repository synergism therapy design transcriptome translational approach

项目摘要

The overall goal of the CWRU Psoriasis Center of Research Translation (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 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 repurposed 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; and the 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 novel pathways in psoriasis pathogenesis that are likely to benefit from intervention by new or repurposed drugs that will translate to psoriasis therapy. Our overarching hypothesis is that we can powerfully combine existing and developing psoriasis basic science datasets, patient records, bioinformatics and computational systems biology with bi-directional mouse and human studies to identify new therapeutic targets and repurposed drugs that can be expeditiously moved to clinical trials, improving psoriasis treatment and patient care. To test and refine this hypothesis, the Specific Aims are: (1) Identify new pathways central to psoriasis pathogenesis and new psoriasis drug candidates by analyzing psoriasis patients' EMR data, tissue and blood samples and; (2) Evaluate AMC-identified gene targets and efficacy of pathway-specific drug candidates using preclinical molecular genetic psoriasis mouse models. The concentrated interactions between the CRP and Cores will provide value-added research output, far beyond any incremental advances that a given Core or specific project could provide. Our novel, highly integrated and synergistic CORT design, powered by exceptional resources and expertise of our interdisciplinary translational investigative team, will exert a transformative and sustainable impact on the psoriasis field and patient care.

CWRU银屑病研究翻译中心（CORT）的总体目标是结合新的