Canalicular lipid transporters

The liver is an essential organ for lipid homeostasis and metabolism as well as detoxification. Bile formation and biliary elimination of lipids (e.g., cholesterol) are key elements in lipid homeostasis and detoxification. Interference with bile formation (e.g., by drugs interacting with ABC transporters required for biliary lipid secretion) or changes in lipid homeostasis can lead to cholestatic liver disease (e.g., gallstone disease).

The major goal of this project is the development of novel therapeutic strategies for biliary diseases due to disturbed bile formation. By the use of an established in vitro model system for biliary lipid secretion, small molecule activators targeting key transporters involved in bile formation will be developed, capable to increase the solubility of cholesterol in bile. For a mechanistic understanding of compound-target interaction, overexpressed, purified and reconstituted protein will be used.