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How do variations in genes contribute to altered pharmakokinetics and drug response ?

We are interested in basic mechanisms that lead to inter- and intraindividual differences in the biotransformation of drugs and other xenobiotics. Because most of this takes place in the liver, we established a large human liver bank, now consisting of about 300 clinically well documented surgical samples. These tissue samples allow us to study enzymatic functions of every drug metabolizing enzyme, its population variability, as well as genotype-phenotype relationships and drug-drug interactions. Based such in vitro studies we extrapolate to the in vivo situation, we conduct volunteer studies to validate our results, and clinical studies to assess their clinical value. Recently we extended our strategies to include genome-wide technologies, aiming at a comprehensive analysis of all relevant genes. Furthermore, in the network HepatoSys we use human primary hepatocytes to study time-dependent processes such as gene induction or repression.
Major Projects
  • Pharmacogenomics of drug metabolizing cytochromes P450 in human liver
  • Regulation of ADME genes
  • Sex differences in human drug metabolism
  • Systems biology approaches to drug metabolism in human hepatocytes
  • Exploitation of genome-wide technologies for interindividual variability
Ulrich M. Zanger
   Ulrich M. Zanger
Group Members

Senior Research Scientist

Post Doctoral Scientist

 PhD students  Diana Feidt, Stephan Riedmaier, Jessica Rieger
 Diploma students  Bernhard Kandel, Alice Klär
 Technicians  Britta Klumpp, Igor Liebermann
Selected References
  • Riedmaier S, Klein K, Hofmann U, Keskitalo JE, Neuvonen PJ, Schwab M, Niemi M, Zanger UM: UDP-Glucuronosyltransferase (UGT) Polymorphisms Affect Atorvastatin Lactonization In Vitro and In Vivo. Clin Pharmacol Ther 2010;87:65-73
  • Zanger UM, Turpeinen M, Klein K, Schwab M: Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Anal Bioanal Chem 2008; 392(6):1093-1108
  • Schwab M, Zanger UM, Marx C, Schaeffeler E, Klein K, Dippon J, Kerb R, Blievernicht J, Fischer J, Hofmann U, Bokemeyer C, Eichelbaum M; German 5-FU Toxicity Study Group: Role of Genetic and Nongenetic Factors for Fluorouracil Treatment-Related Severe Toxicity: A Prospective Clinical Trial by the German 5-FU Toxicity Study Group. J Clin Oncol 2008; 26:2131-8
  • Rotger M, Tegude H, Colombo S, Cavassini M, Furrer H, Decosterd L, Blievernicht J, Saussele T, Gunthard HF, Schwab M, Eichelbaum M, Telenti A, Zanger UM: Predictive value of known and novel alleles of CYP2B6 for efavirenz plasma concentrations in HIV-infected individuals. Clin Pharmacol Ther 2007;81:557-66
  • Toscano C, Klein K, Blievernicht J, Schaeffeler E, Saussele T, Raimundo S, Eichelbaum M, Schwab M, Zanger UM: Impaired expression of CYP2D6 in intermediate metabolizers carrying the *41 allele caused by the intronic SNP 2988G>A: evidence for modulation of splicing events. Pharmacogenet Genomics 2006;16:755-66
  • Klein K, Lang T, Saussele T, Barbosa-Sicard E, Schunck WH, Eichelbaum M, Schwab M, Zanger UM: Genetic variability of CYP2B6 in populations of African and Asian origin: allele frequencies, novel functional variants, and possible implications for anti-HIV therapy with efavirenz. Pharmacogenet. Genomics 2005;15:861-73
Major Networks and Collaborations
  • HepatoSys, German Network for systems biology of the liver
  • Prof. Andreas Nüssler, Technical University of Munich
  • Dr. Michael S. Phillips, Head of the Pharmacogenomics Centre at McGill University and Genome Quebec
  • Dr. Jörg Lippert, Head of the Systems Biology Section of Bayer Technology Services at Leverkusen
Extramural Funding
  • BMBF (Federal Ministry of Education and Research), HepatoSys Network for systems biology of the liver