The intestinal epithelium undergoes continuous, rapid cellular turnover, making it a paradigmatic model for the study of tissue renewal and regeneration. Intestinal stem cells (ISCs), which are marked by the gene Lgr5, can differentiate along all intestinal epithelial cell lineages. Cell fate decisions are controlled by a delicate balance between high Wnt activity at the crypt bottom, where Lgr5+ ISCs reside, and increasing BMP levels as cells exit the crypt.
The ISC niche is comprised of various cell types, including mesenchymal, immune, nervous system, and endothelial cells, which all play a role in maintaining the physiological function of the intestine. Our research is focused on fundamental questions in the field, including the identity, regulation and plasticity of intestinal stem cells, as well as how these stem cells behave after injury. We utilize mouse and organoid models to advance our understanding of intestinal development and function during homeostasis and regeneration.
Some of our current interests include:
- Understanding how villi are built in the embryo.
- Modeling Inflammatory Bowel Disease using human induced pluripotent stem cells and mouse models.
- Dissecting the role of the intestinal niche in regeneration.
- Understanding how the morphology of intestinal epithelial crypts influences the tissue’s regenerative capacity.
- Determining the role of polarity genes in regulation of intestinal homeostasis.
- Investigating regional patterning across the length of the small intestine