| 1. The physiological function of ATP8B1. We have discovered that this lipid flippase (which is deficient in an inherited form of cholestasis) needs at least one accessory protein from the small family of CDC50 proteins to be properly targeted to the plasma membrane. In the presence of this protein flippase activity can be assayed enabling us to screen the effect of mutations. Also the CDC genes are now candidates as causative genes for cholestatic disorders. 2. Cholestatic pruritus. We have started a research line into the mechanism of pruritus (itch) in many cholestatic disorders. Assays are being set up to analyze the effect of cholestatic factors (such as bile salts) on neuronal signalling. 3. Development of a liver function test. In collaboration with a pharmaceutical company we have analyzed the mechanism of clearance of a fluorescent bile salt analog that is under development as a liver function test. 4. Bioartificial liver support; hardware: The AMC bioartificial liver has been evaluated by 3D numerical modeling and computational simulation: resulting in improved oxygenation capacity by increased oxygen capillaries and thinner matrix. Comparable function of AMC-BAL and Berlin BAL (MELSS); cells: Immortalised human fetal liver cell line (cBAL111), patent pending. Improvement of differentiation grade |
