Regeneration and cell fate in the intrahepatic bile ducts

The liver is key regulator of organismal homeostasis and is well known for its remarkable ability to regenerate following physical injury or chemically induced damage. However, evidence suggests that all epithelial regeneration in the adult liver is drive by mature hepatocytes and biliary epithelial cells (BECs) rather than a dedicated stem cell pool. In cases of chronic or severe injury, cells can transdifferentiate between hepatocyte and BEC lineages. We are pursuing a deeper understanding of transcriptional and chromatin regulation of BECs during homeostasis and following injury. We are particularly interested in the mechanisms regulating BEC proliferation and transdifferentiation during ductular reaction, an extensive remodeling and expansion of the intrahepatic bile ducts that occurs in acute and chronic liver injury. 

We are also applying tools and techniques developed in our studies of intestinal stem cells (ISCs) to understand BEC heterogeneity. Our long-term goal is to better understand functional and genomic heterogeneity among BECs to advance our understanding of hepatobiliary disease to inform the development of novel therapeutics.