Progressive Familial Intrahepatic Cholestasis

Progressive familial intrahepatic cholestasis (PFIC) is a group of rare, inherited liver disorders that disrupts the normal bile flow, leading to the accumulation of bile acids in liver. This buildup causes progressive liver damage and can result in cirrhosis and liver failure. Currently, the only effective treatment is liver transplantation.

Our lab focuses on two subtypes of PFIC:

• PFIC1, caused by mutations in the ATP8B1 gene, which encodes the phospholipid flippase FIC1.
• PFIC2, caused by mutation in the ABCB11 gene, which encodes the bile salt export pump (BSEP).

Using CRISPR/Cas9 genome editing, we generated atp8b1 and abcb11b knockout mutant zebrafish, which develop severe cholestasis similar to human patients. We also developed assays to introduce missense variants identified in patients into zebrafish to study their biological consequences. These models allow us to investigate disease mechanisms and identify potential therapeutic targets for new treatments.