Pharmacology, Toxicology and Therapeutics : People : Bruno Hagenbuch
Research Interests
Organic Anion Transport, Bile Acid Transport, Transport Physiology,
Hepatic Drug Clearance
Transport proteins are required for the proper function of cells because they control the selective transport of molecules across membranes. For example, transport proteins allow cells to take up nutrients or drugs and to discard toxic waste products. nactivation of transport proteins because of interactions with other substrates or because of mutations can lead to serious clinical disorders. A special family of transporters that we initially identified in the liver is the family of the organic anion transporting polypeptides (rodent: Oatps, human: OATPs). They transport numerous structurally unrelated endo- and xenobiotics into hepatocytes and have been the major focus of my research over the last 10 years.
My current research addresses the following questions: 1) what are the molecular properties of the broad substrate specificity of most OATPs; 2) what structural requirements make a compound an OATP substrate; and 3) do OATPs transport nuclear receptor ligands and does co-administration of such ligands with other drugs, which are cleared by OATPs, lead to adverse drug-drug interactions?
To answer these questions I will use functional expression systems, such as transfected cell lines and the Xenopus laevis oocytes system together with molecular biology and computer modeling.
Kullak-Ublick, G.A., Ismair, M.G., Stieger, B., Landmann, L.., Huber, R., Pizzagalli, F., Fattinger, K., Meier, P.J. and Hagenbuch, B. (2001) Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 120: 525-533
Cattori, V., van Montfoort, J.E., Stieger, B., Landmann, L.., Meijer, D.K.F., Winterhalter, K.E., Meier, P.J. and Hagenbuch, B. (2001) Localization of organic anion transporting polypeptide 4 (Oatp4) in rat liver and comparison of its substrate specificity with Oatp1, Oatp2 and Oatp3. Pflügers Arch. 443: 188-195
van Montfoort, J., Schmid, T.E., Adler, I.D., Meier, P.J. and Hagenbuch, B. (2002) Functional characterization of the mouse organic anion transporting polypeptide 2. Biochim. Biophys. Acta. 1564: 183-188
Pizzagalli, F., Hagenbuch, B., Stieger, B., Klenk, U., Folkers, G. and Meier, P.J. (2002) Identification of a novel human organic anion transporting polypeptide (OATP-F) as a high affinity thyroxine transporter. Mol. Endocrinol. 16: 2283-2296
Hagenbuch, B. and Meier, P.J. (2003) The superfamily of organic anion transporting polypeptides. Biochim. Biophys. Acta. 1609: 1-18
Hagenbuch, B. and Meier, P.J. (2004) Organic anion transporting polypeptides of the OATP/ SLC21 family: phylogenetic classification as OATP/ SLCO superfamily, new nomenclature and molecular/functional properties. Pflügers. Arch. 447:653-665.
Meier-Abt F., Faulstich, H. and Hagenbuch, B.(2004) Identification of phalloidin uptake systems of rat and human liver. Biochim. Biophys. Acta. 1664: 64-69
Yarim, M., Moro, S., Huber, R., Meier, P.J., Kaseda, C., Kashima, T., Hagenbuch, B. and G. Folkers, (2005) Bioorg. Med. Chem. 13:463-471
Fischer, W.J., Altheimer, S., Cattori, V., Meier, P.J., Dietrich, D.R. and Hagenbuch, B. (2005) Organic anion transporting polypeptides expressed in liver and brain mediate uptake of microcystin. Toxicol. Appl. Pharmacol. 203:257-263
Bruno Hagenbuch, Ph.D.
Professor
Department of Pharmacology, Toxicology and Therapeutics
The University of Kansas Medical Center
MS 1018
3901 Rainbow Boulevard
Kansas City, Kansas 66160
Phone: (913) 588-0028
Fax: (913) 588-7501
Email: bhagenbuch@kumc.edu
Updated 08/12/2005
©
The University of Kansas Medical Center