Stieger Bruno

Group Leader

Prof. Dr. sc. nat. Bruno Stieger

 

Name of the Institution

Department of Clinical Pharmacology and Toxicology

University Hospital Zurich

Raemistrasse 100

8091 Zurich

Switzerland                                                                                                                                                                                                                                                                                                                                                                                                

Phone +41 44 634 31 69

Email bruno.stieger@uzh.ch

 

Group Members

dipl. pharm. Zainab Blattmann-Mahdi, PhD student, Zainab.Mahdi@usz.ch

Stephanie Bernhard, technical assistant, StephanieAngelina.Bernhard@usz.ch

Main Field(s) of Research, Abstract

The main research of the group is focused on the intraction of drugs and imaging agents with hepatocellular transporters and on mechanisms of lipid secretion from hepatocytes into bile. To address the first question, we use cell lines stably transfected with uptake transporters and insects cells together with the baculoviurs system for efflux transporters. A major focus of this work is to study the role of drug-transporter interactions in the pathogenesis of drug-induced liver injury. To study canalicular lipid secretion, we work on the proteome of the rat canalicular membrane. In addition, we have established several model cell lines, which are currently used to study details of canalicular phospholipid and cholesterol secretion.

Main Fields of Research, Keywords

hepatocanalicular ABC transporters, bile formation, biliary lipid secretion, drug-transporter interaction, physiology and pathophysiology of liver

Special Techniques and Equipment

antibody generation (polyclonal and monoclonal), subcellular fractionation, lipid analysis,

Education and Training

Forschungsseminar Klinische Pharmakologie und Experimentelle Hepatologie

Selected Publications

Stieger B., and Gao B. (2015) Drug transporters in the central nervous system. Clin. Pharmacokinet. 54, 225-242.

Guyot C., Hofstetter L., and Stieger B. (2014) Differential effects of membrane cholesterol content on the transport acitivity of multidrug resistance associated protein 2 (ABCC2) of the bile bile salt export pump (ABCB11). Mol. Pharmacol. 85, 909-920.

Pastor C.M., Mühaupt B., and Stieger B. (2014) The role of organic anion transporters in diagnosing liver diseases by magnetic resonance imaging. Drug Metab. Disp. 42, 675-684.

Wlcek K., Koller F., Ferenci P., and Stieger B. (2013) Hepatocellular organic anion-transporting polypeptides (OATPs) and multidrug resistance-associated protein 2 (MRP2) are inhibited by silibinin. Drug Metab. Disp. 41, 1522-1588.

Hagenbuch B., and Stieger B. (2013) The SLCO (former SLC21) superfamily of transporters. Mol. Asp. Med. 34, 396-412.

Stieger B., Heger M., de Graaf W., Paumgartner G., and van Gulik T. (2012) The emerging role of transport systems in liver function tests. Eur. J. Pharmacol. 675, 1-5.

Guyot C., and Stieger B. (2011) Interaction of bile salts with canalicular membrane vesicles: evidence for bile salt resistant microdomains. J. Hepatol. 55, 1368-1376.

de Graaf W., Häusler S., Heger M., van Ginhoven T.M., van Cappellen G., Bennink R.J., Kullak-Ublick G.A., Hesselmann R., van Gulik, T.M. and Stieger B. (2011) Transporters involved in the hepatic uptake of (99m)Tc-mebrofenin and indocyanine green. J. Hepatol. 54, 738-745.

Stieger B. (2011) The role of sodium-taurocholate cotransporting polypeptide (NTCP) and of the bile salt export pump (BSEP) in physiology and pathophysiology of bile formation. Handb. Exp. Pharmacol. 201, 205-259.

Stieger B. (2010) Role of the bile salt export pump, BSEP, in acquired forms of cholestasis. Drug Metab. Rev. 42, 437-445.

Ismair M.G., Häusler S., Stuermer C.A., Guyot C., Meier P.J., Roth J., and Stieger B. (2009) ABC-transporters are localized in caveolin-1-positive-and reggie-1-negative and reggie-2-negative microdomains of the canalicular membrane in rat hepatocytes. Hepatology 49, 1673-1682.

Leuthold S., Hagenbuch B., Mohebbi N., Wagner C.A., Meier P.J. and Stieger B. (2009) Mechanisms of pH-gradient driven transport mediated by organic anion transporting polypeptide transporters. Am. J. Physiol. C570-C582.

Treiber A., Schneiter R., Häusler S., and Stieger B. (2007) Bosentan is a substrate of human OATP1B1 and OATP1B3: Inhibition of hepatic uptake as the common mechanism of its interaction with cyclosporine A, rifampicin, and sildenafil. Drug Metab. Disp. 35, 1400-1407.

Stieger B, Meier Y., and Meier P.J. (2007) The bile salt export pump. Pflügers Arch. 453, 611-620

Meier Y., Pauli-Magnus C., Zanger U.M., Klein K., Schaeffeler E., Nussler A.K., Nussler N., Eichelbaum M., Meier P.J., and Stieger B. (2006) Interindividual variability of canalicular ATP-binding cassette (ABC)-transporter expression in human liver. Hepatology 44, 62-74.

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.

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

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.

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, NCCR TransCure