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Research in the Ghanem Lab involves several active projects, including inflammatory bowel disease (IBD) tissue biomarker discovery, IBD risk variant-to-effector gene mapping studies, and the role of RNA-binding proteins on T cell function and differentiation as well as maintenance of the intestinal epithelium.
Current pediatric IBD biomarkers and clinical data have a limited ability to predict aggressive disease behavior and treatment response. Thus, there is a need to identify superior biomarkers to improve the diagnosis and treatment of children with IBD. The Ghanem Lab is developing computational models that predict IBD disease progression by combining clinical and genetic data with gene expression and mRNA alternative splicing data from intestinal biopsies.
Genome-wide association studies (GWAS) have identified more than 200 IBD genetic risk loci. However, GWAS only report genomic signals associated with a given trait and not necessarily the precise location or the precise tissues in which they are active, nor do these signals identify culprit genes in most instances. The lab is therefore working to identify and characterize the function of causal variants at IBD-associated GWAS loci, as well as identify their corresponding effector genes, in the intestinal epithelium.
In addition, the Ghanem Lab is studying the role of the Poly(c) binding protein family (Pcbp) of RNA-binding proteins on T cell function and inflammation. CD4+ T cells drive mucosal inflammation in IBD. This study uses animal models to better understand how post-transcriptional gene regulation mediated by Pcbp:RNA interactions controls CD4+ T cell activation and intestinal inflammation.
The human intestinal epithelium is replenished every 5-7 days and depends upon intestinal stem cell renewal and progenitor cell expansion for proper function. The Ghanem lab is using animal models and intestinal epithelial stem cell cultures termed "enteroids" to understand how mRNA processing controlled by Pcbp proteins impacts stem cell function and progenitor cell differentiation.