If the intestinal epithelium was unraveled it would be a one-cell-thick layer with enough surface area to cover a tennis court. This thin layer selectively absorbs nutrients while repelling toxins and pathogens. Because it’s a dirty job, the entire epithelium is shed and replenished continuously (much like our skin) with the entire epithelium replaced every few days. High exposure to noxious substances coupled with high rates of proliferation make this epithelial layer susceptible to both cancer and inflammatory disease. Intestinal diseases are among the most prevalent maladies in our society.
Our group investigates how transcription factors, co-regulators, and specific chromatin structures are assembled into enhanceosomes, multiprotein complexes that control gene expression over distances of many kilobases. These complexes are scattered throughout our genomes, selectively reading the genetic code and the epigenetic landscape to allow the cell to integrate external stimuli and respond with genomic output. Different combinations of transcription factors, co-regulators, and chromatin modifications can respond uniquely to cellular states and our goal is to understand the rules via which these complexes operate. We discover these processes in the healthy intestinal epithelium and then dissect each component part using mouse genetics. We then compare how these processes are disrupted in intestinal disease with the goal of unraveling the causes and discovering the cures for intestinal health.