Zentrum für Klinische Forschung

 

Stieger Bruno

Group Leader

Prof. Dr. Bruno Stieger

 

Stieger

Name of the Institution

Clinical Pharmacology and Toxicology
University Hospital Zurich

Street

Rämistrasse 100

City

8091 Zürich

Phone

+41-44-634 31 69

E-mail

bstieger@kpt.uzh.ch 

Group Members

Dr. Melissa Mock, PhD, mmock@kpt.uzh.ch
Dr. Marguerite Anne Sidler Pfändler, postdoc, masidler@kpt.uzh.ch
Dr. Igor Marsteller, postdoc marsteller@access.uzh.ch
dipl. pharm. Yvonne Meier, PhD student, yvonne.meier@DIM.USZ.ch

Main Field(s) of Research, Abstract

The main focus of the group is on liver progenitor cells and bone marrow derived stem cells. The liver has a significant potential for regeneration. If up to 60 % of the liver is removed by partial hepatectomy, remaining hepatocytes rapidly divide and replace the lost liver mass. In contrast, if the liver gets damaged by toxic insults, the capacity of liver regeneration is often not sufficient to regenerate damaged liver cell mass. This aspect is poorly understood and in particular, cells capable of liver regeneration in this situation are not unequivocally identified. Our approach to study these questions is to follow a) the dedifferentiation of primary cultured rat hepatocytes; b) to study the expansion and differentiation of hepatocyte progenitor cells (so called "small hepatocytes") in culture; and c) to study the potential of subpopulations of bone marrow derived stem cells to become hepatocyte progenitor cells. We follow especially the expression of basolateral and canalicular bile salt transport systems as hepatocellular differentiation markers. In mature hepatocytes these polarized transport systems play an important role in bile formation. Furthermore, defective expression and/or altered functions of canalicular ABC (ATP-Binding-Cassette) transporters can be the cause of hereditary and acquired forms of cholestatic liver diseases. It is therefore important to know the molecular transport physiology and regulation of expression of the canalicular ABC transporters in liver progenitor cells and mature hepatocytes.

Main Fields of Research, Keywords

primary liver cell culture, liver progenitor cells, bone marrow derived stem cells, protein-protein interactions, hepatocanalicular ABC transporters

Special Techniques and Equipment

antibody generation, subcellular fractionation, primary liver cell culture, lipid analysis, free flow electrophoresis

Education and Training

Forschungsseminar Klinische Pharmakologie und Experimentelle Hepatologie Hepatologisches Forschungsseminar Praktikum in Zellphysiologie im Rahmen des Postgraduate Kurs für experimentelle Medizin und Biologie

Selected Publications

Noé, J., Stieger B., and Meier, P.J. (2002) Functional expression of the canalicular bile salt export pump of human liver. Gastroenterology 123, 1659-1666 (2002).

Cao, J., Stieger, B., Meier, P.J., and Vore, M. (2002) Expression of rat hepatic multidrug resistance-associated proteins and organic anion transporters in pregnancy. Am. J. Physiol. 283, G757-G766.

Meier, P.J. and Stieger, B. (2002) Bile salt transporters. Annu. Rev. Physiol. 64, 635-661.

Rippin, S.J., Hagenbuch, B., Meier P.J., and Stieger B. (2001) Cholestatic expression pattern of sinusoidal and canalicular organic anion transport systems in primary cultured rat hepatocytes. Hepatology 33, 776-782.

Dürr, D., Stieger, B., Kullak-Ublick, G.A., Rentsch, K.M., Steinert, H.C., Meier, P.J., and Fattinger, K. (2000) St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin. Pharmacol. Ther. 68, 598-604.

Rahner, C., Stieger B., and Landmann, L. (2000) Apical endocytosis in rat hepatocytes in situ involves clathrin, traverses a subapical compartment, and leads to lysosomes. Gastroenterology 119, 1692-1707.

Fattinger, K., Cattori, V., Hagenbuch, B., Meier, P.J., and Stieger, B. (2000) Rifamycin SV and rifampicin exhibit differential inhibition of the hepatic rat organic anion transporting polypeptides, Oatp1 and Oatp2. Hepatology 32, 82-86.

Madon, J., Hagenbuch, B., Landmann, L., Meier, P.J., and Stieger B. (2000) Transport function and hepatocellular localization of mrp6 in rat liver. Mol. Pharmacol. 57, 634-641.

Stieger, B., Fattinger, K., Madon, J., Kullak-Ublick, G.A., and Meier, P.J. (2000) Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver. Gastroenterology 118, 422-430.

Funding

Swiss National Science Foundation

URL

http://www.pharmakologie.unispital.ch 

Link to "Forschungsdatenbank" of the University

http://www.research-projects.uzh.ch/a401.htm