Notch Signaling is Essential to Modulate Intrahepatic Bile Duct Structure
Sparks, Erin Elizabeth
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2011-03-14
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.