Core 1: Pre-clinical Modeling Core

Ward, Nicole

Abstract

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.