Inflammatory Bowel Disease (IBD) comprises incurable chronic diseases of the gut which oscillate between periods of disease worsening (i.e. relapse) and relatively normal health (i.e. remission). Whilst current medicines often reduce this see-sawing problem, their effectiveness eventually wanes to the point where a large percentage of IBD patients still need hospitalisation and major surgery during […]
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 […]
Sorbitol is a sugar alcohol that is not absorbed very well in our bodies. It is usually broken down in the gut by a type of bacteria called Clostridia. When these bacteria are not there, sorbitol accumulates and that leads to increased osmotic stress for the cell lining our intestines. Our cells have many defense […]
The intestinal immune system must maintain a delicate balance between harmless bacteria in the gut and immunity against dangerous pathogens. Dysregulation of this balance can lead to Inflammatory Bowel Diseases (IBD) such as ulcerative colitis (UC) and Crohn’s disease. Many treatments for IBD focus on blocking inflammation and fail to repair damaged tissue and restore […]
The epithelial cells lining the intestine control responses to gut bacteria, limiting intestinal damage in Crohn’s disease. A critical gene in this pathway is DUOX2, which is up-regulated in response to bacteria, and helps maintain intestinal health. We discovered that Crohn’s disease patients who carry genetic variants in DUOX2 are more likely to progress to […]
Various immune cells in the gut recognize and respond to microbes that live there, which are collectively known as the gut microbiota. This project focuses on a subset of immune cells termed B cells, which are important for functions such as antibody production. In particular, we are investigating how certain kinds of beneficial gut bacteria […]
Our gut is constantly exposed to environmental harms, such as bacteria and dietary products, among others. The epithelium layer of our intestinal tract, which is the most exposed to the external world, contains a variety of immune cells, which likely play an important role in patrolling and defending our intestine. However, how these cells protect […]
Ulcerative colitis (UC) is a chronic inflammatory disorder that affects the colon. There are multiple types of cells that drive inflammation and injury to the lining of the colon. Vedolizumab (VDZ) is a medication that blocks circulating immune cells from gaining access to the colon, but there are conflicting data about the primary cell types […]
Inflammatory Bowel Disease (IBD) is caused by multiple genetic and environmental factors but the molecular mechanisms leading to chronic inflammation in the gut are largely not understood. Much of the heritable human risk for IBD, particularly in Crohn’s disease, can be mapped to defects in lysosomes, a cellular organelle responsible for bacterial degradation. Previous studies […]
In Inflammatory Bowel Disease (IBD), inflammation of the digestive tract lining results in the development of chronic ulcers appearing throughout the intestines, colon or rectum. Although symptoms of IBD can be managed through the use of corticosteroids, complete disease remission is rare, often leading to surgical intervention. High expression of the transcription factor HIF-1_ is […]