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. […]
Accumulating data supports the concept that IBD has a preclinical period that may be amenable to early diagnosis and intervention. Understanding the molecular underpinnings of this preclinical period in disease pathogenesis offers new opportunities in risk prediction and prevention. We have recently reported the first data from a large study using longitudinal pre-diagnostic samples from […]
Inflammatory Bowel Disease (IBD) is associated with currently untreatable conditions such as fibrosis and strictures that arise as a consequence of aberrant wound healing. It is of utmost importance that we understand the biology of normal wound healing and discover why IBD is associated instead with abnormal wound healing. Immune cells called macrophages help sense […]
Crohn’s disease is a chronic inflammatory disease of the intestinal tract. It has been increasingly appreciated that two factors are involved beyond the genetic setup of individuals: 1.) Intestinal microbial dysbiosis and 2.) immune system dysregulation. Intestinal microbial dysbiosis refers to changes in the billions of bacteria that are growing in our gut. In healthy […]
Fat tissues are known to regulate the storage and release of fatty acids. However, their role in the context of intestinal inflammation remains largely unclear. Interestingly, abdominal fat tissue expands in many Crohn’s disease patients engulfing parts of the inflamed intestine. This has recently been associated with the promotion of pro-repair mechanism helping to heal […]
