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) may lead to acquired forms of liver disease.

The human MDR3 (ABCB4), a member of the multidrug resistance protein family, and the ABC transporters ABCG5 and ABCG8 are found to play a major role during canalicular lipid secretion where MDR3 translocates phospholipids and ABCG5/G8 facilitate bilary cholesterol secretion.

We plan to establish a reliable assay system modeling canalicular lipid secretion and to evaluate this system for the utility to check drugs for inhibition of MDR3 and ABCG5/G8.

This will allow testing whether such drug may lead to acquired liver disease. We will also test the hypothesis that endocannabinoids and cholesterol are cotransported by ABCG5/G8.