Notch Signaling is Essential to Modulate Intrahepatic Bile Duct Structure

Abstract

Cholangiopathies, or diseases which affect the biliary epithelial cells of the liver, are an important health concern in the United States. Specifically, the diagnosis of a cholangiopathy is the number one indicator of pediatric liver transplant and the number three indicator for adults. A common clinical finding in cholangiopathies is cholestasis or reduced bile flow, however the specific pathogenesis of most cholangiopathies is largely unknown. A subtype of cholangiopathy, which this research focuses on, is the genetic cholangiopathy. One specific example of a genetic cholangiopathy is Alagille syndrome, a pleiotropic disorder primary characterized by a lack of bile ducts. Alagille syndrome is highly associated with mutations in the Notch signaling pathway. In this dissertation, I use mouse models that modulate Notch signaling to define the developmental and post-natal mechanism of cholestasis in a cholangiopathy model.