Category(ies) of Research
Descriptor of Research
The primary focus of my laboratory is how gene-environment interplay modulates gut innate immunity. Our initial studies centered on Paneth cells, a key epithelial cell type in the small intestine that has important role in innate immunity. We showed that defective Paneth cells are associated with poor clinical outcome in patients with Crohn’s disease (CD). We showed that both CD and non-IBD patients that were overweight or obese were more likely to develop Paneth cell defects. Using mice fed with western diet, we further showed that this was due to activated FXR signaling (due to increased production of secondary bile acid deoxycholic acid) in the gut and myeloid cells, the latter of which also induced Type I interferon, and the parallel activation of FXR and Type I interferon pathways jointly triggered Paneth cell defects. This work was published last year (PMID: 34010595). Moving forward, we are interested in understanding how high dietary fructose modulates Paneth cell function, to the extent hepatic FXR signaling may be used as a therapeutic target, and how long-term western diet consumption affects Paneth cell and intestinal stem cell differentiation.