Inflammation is an integral part of immune defense against pathogens or tissue damage. However, inappropriate or prolonged inflammation has deleterious consequences and underlies many chronic diseases, especially inflammatory bowel diseases (IBD) like Crohn’s disease and colitis. Specialized immune sensors that reside inside the cell cytosol are of particular interest in IBD, because mutations in the […]

Individuals with mutations in the receptor for IL-10 suffer from very early onset Inflammatory Bowel Disease. These patients are typically unresponsive to conventional therapies and have a poor long-term prognosis. The only available curative therapy is bone marrow transplantation from a suitable donor, which carries significant risks and often is not available. We propose to […]

Inflammatory Bowel Disease (IBD) is characterized by chronic intestinal inflammation, which causes damage to the intestinal epithelium. This inflammatory response in the small and large bowel is thought to be initiated by interactions between genes, environment, and microbes, which reside in the gastrointestinal tract. However, the mechanisms by which environmental factors modulate susceptibility to IBD […]

Inflammatory Bowel Disease (IBD) is caused by the accumulation of genetic, microbial and lifestyle factors that increase the susceptibility to the disease beyond a red line. The number and complexity of such factors makes prediction of pathogenesis and therapy particularly difficult. Nevertheless, clinical and experimental observations demonstrate a strong association of early life events with […]

Genome wide association studies (GWAS) show that the human gene ITLN1 is associated with Crohn’s disease. A common form of this gene is present in a substantial fraction of individuals with the disease. The functional significance of this association is unknown. A critical step in using genetic information to develop treatments with the potential to […]

Microbial communities living on the surfaces of the mammalian intestinal tract likely play a role in Inflammatory Bowel Disease (IBD), but this role is not yet fully understood. We will develop two innovative technologies that will help researchers visualize and quantify which microbes live on intestinal surfaces, where these microbes are located relative to each […]

In IBD, the microbes within the intestinal tract, collectively known as the microbiota, are targeted by inappropriate immune responses. There are also a number of changes in the microbiota composition that are thought to drive or amplify IBD pathology. One of these is the expansion of E. coli. However, our preliminary data has identified select […]

Gut inflammation alters the bacterial communities in the gut (the microbiome), and these disruptions are thought to make inflammation even worse. Understanding and derailing this cycle could provide new avenues for IBD therapy. Although we know that inflammation can change “who’s there” in the gut microbiome, this project will determine whether harder-to-measure changes within the […]

We have discovered a novel single-gene defect in patients with pediatric IBD, setting the stage for new molecular and cellular discoveries to dissect biology stemming from human disease. Here, we will pursue two aims that will open new doors by leveraging the strength of preclinical models to uncover mechanisms by which the gene we identified […]

Inflammatory Bowel Diseases (IBDs) are typified by bouts of inflammation-induced epithelial damage and repair. By take cues from their microenvironment or “niche”, intestinal stem cells (ISCs) direct these fluctuating pathological and reparative states in IBD. Yet, we do not understand which cells comprise the inflamed ISC niche and how they switch on programs of repair. […]