The main focus of my postdoctoral research was to identify mechanisms that regulate embryonic development of the intestine and colon, and to apply this information towards the generation of human colonic organoids. To do this I established a collaborative program that combined the strengths of frog and mouse models with human pluripotent stem cell-derived gut tube cultures. We identified BMP as an evolutionarily conserved pathway for the induction of a posterior HOX code in the gut tube. A brief BMP-patterning step was essential for the development of human colonic organoids (HCOs). HCOs contained cell types consistent with colonic identity and, following transplantation under the mouse kidney capsule, further matured into colon-like structure with well-differentiated smooth muscle layers.
HCOs should provide and excellent model for studying human colonic development and disease in a dish. Using HCOs, my lab is working elucidate molecular mechanisms of congenital diseases that affect the colon using patient specific or CRISPR-Cas9 edited induced pluripotent stem cell (IPSC) derived HCOs. We’ve recently discovered that HCOs also contain immune cells which co-develop within the organoid mesenchyme. The presence of immune cells in HCOs should allow us to study signaling networks between the epithelium, mesenchyme and immune cells. This work should lead to new insights into diseases such as polyposis syndromes and inflammatory bowel disease.