The primary goal of Core B is to provide individual projects with intestinal tissue, isolated cell populations, and functional genomic information from clinically characterized IBD patients and healthy controls. This core will overcome a widely acknowledged roadblock in the use of animal models - direcfing animal research to address questions that will be directly translatable to human IBD. The data and tissue banks and novel technologies developed through this core will allow investigators the opportunity to correlate molecular findings across model species to human diseases. Core B will leverage substanfial existing resources and expertise at UNC. There is an established infrastructure for obtaining and processing surgical resecfions and intestinal biopsies. The Tissue component of Core B will process and provide frozen intestinal tissue; RNA and protein extracts from intestinal tissue, deidentified clinical information on disease phenotype, and at the request of invesfigators, isolated intestinal cell populations. Where required, the core will be able to provide matched serum in peripheral blood mononuclear cell populafions as well as DNA to correlate immunophenotype, clinical phenotype with genetic background. Understanding the molecular basis of human IBD is far from being achieved. High throughput assays that permit the identification of gene regulatory networks in a heterogeneous disease like IBD is of paramount importance to elucidate the pathogenic mechanisms of IBD and for the development of diagnostic tools and of innovative therapeutics. The Genomics component of Core B will use complementary high throughput assays of chromatin status (FAIRE, and ChIP) and gene expression (RNA) from isolated single cells (murine and human), and clinically phenotyped pafients combined with deep sequencing. Each Project profits by centralized data processing and analysis that increases feasibility and efficiency, decreases costs for each Program Project investigator and limits variations that may occur from technical error. Furthermore, Core B capitalizes and builds on the financial commitments and technical expertise already made by the NIH (ENCODE, 1000 genomes, and HapMap projects) and the Carolina Center for Genome Sciences. Data generated by Core B will allow each investigator to study active regulatory elements in the genome at a level of detail yet to be performed.
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