WNT2B in the Intestine

Role of Wnt2b in intestinal development

We initially characterized human Wnt2b deficiency, which features severe neonatal onset diarrheal disease and dysregulation of the intestinal and colonic epithelium. Our ongoing studies have shown that WNT2B is important for epithelial development in humans, and is important for healthy intestinal stem cells. We have also shown that WNT2B protects against intestinal inflammation in later stages of development. Ongoing work in the lab continues to understand how WNT2B contributes to and regulates these components of intestinal homeostasis.

Role of WNT2B in colon cancer

Wnts signaling is known to be critical in the development of colon cancer. Colon cancer is much more common than small intestinal cancer, but the reason for this is not totally clear.  WNT2B is expressed much more highly in the colon than in the small intestine, and we think regional variation in WNT2B may enhance the susceptibility of the colon to metastatic transformations. We are examining the importance of WNT2B in colon cancer development and metastasis.

Understanding the Premature Intestine

Role of WNT2B in necrotizing enterocolitis

Wnt signaling may also help to protect against an intestinal disease in premature infants called necrotizing enterocolitis. We have determined that neonatal mice lacking WNT2B are more susceptible to NEC, and are working to characterize the importance of Wnt signaling in protecting the developing intestine from injury.

Postnatal Intestinal Modulation in Prematurity

Premature Infants also experience other intestinal diseases including poor nutritional absorption and feeding intolerance. We are aiming to evaluate how postnatal exposures modulate the developing premature human intestine, with a goal of finding ways to improve clinical outcomes for the gut health of premature infants.

Characterizing Novel Orphan Diseases

ORP5 Deficiency

Our lab has identified a novel inborn error of immunity featuring T cell dysfunction, caused by ORP5 deficiency. Ongoing work in the lab aims to further characterize this disease.