Zhao Lab

The primary focus of the Zhao Lab is to use complementary model systems to study human liver diseases, with a particular focus on neonatal cholangiopathy biliary atresia (BA). BA is a complex disease that occurs as result of environmental trigger(s) in genetically susceptible hosts and it is the leading indication for liver transplantation in the pediatric population. While we have established mouse and zebrafish models of BA using a toxin that has been causatively linked to this disease, we are also in the process of establishing an in vitro BA model using cholangiocytes (bile duct cells) derived from human induced pluripotent stem cells (iPSCs). In order to functionally validate genetic variants implicated in human BA, we plan to engineer these mutations into iPSCs using the CRISPR/Cas9 technology and characterize any functional defects in hepatobiliary differentiation as well as assess for increased susceptibility to toxic injury. We will also examine how particular mutations impact responses to therapeutic compounds that we have previously identified. Altogether, we expect a human iPSC-based BA model, once established, to be a powerful tool and a novel assay platform to study the genetic underpinnings of BA, to provide valuable insights into the complex interactions between genetic and environmental risk factors, and develop potential drug treatments for this enigmatic disease.

For more information, visit https://www.zhaolabcolumbia.org/