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Drug Metabolism and Pharmacogenomics

We are interested in the factors that contribute to inter- and intra-individual differences in the biotransformation of drugs and other xenobiotics. Broadly speaking, this includes endogenous and environmental factors, as well as genetic and non-genetic ones. As most of drug metabolism takes place in the liver, we established a large human liver bank, consisting of 300 clinically well documented surgical samples, and we also use human primary hepatocytes as a cellular model. These biological tools, which we obtain from clinical partners throughout Germany, and our unique selection of modern biomolecular technologies allow us to study a variety of phenomena related to drug therapy and response. In particular we analyze the expression and function of enzymes, their population variability, genotype-phenotype relationships, mechanisms of drug-drug interactions, as well as the role of nuclear receptors, microRNAs and other factors in gene regulation. Following up on discoveries in such basic in vitro studies we develop diagnostic assays to evaluate our results in vivo. To assess the clinical value of our findings, we perform volunteer and clinical studies, either in our clinical study unit or in collaboration with our clinical partners. Our aim is thus to contribute to the understanding of variable drug metabolism and drug response, and to move forward the idea of personalized medicine.

Major Projects
  • Biochemistry and pharmacogenetics of human cytochrome P450 monooxygenases
  • Candidate, pathway and whole-genome approaches to inter-individual variability of drug metabolism and drug response
  • Role of transcriptional and microRNA-mediated regulatory mechanisms
  • Systems biology approaches to ADME (absorption, distribution, metabolism, excretion)
Prof. Dr. Ulrich Zanger

phone: ++49-711-8101 3704

Selected References
  • Rieger JK, Reutter S, Hofmann U, Schwab M, Zanger UM. Inflammation-Associated MicroRNA-130b Down-Regulates Cytochrome P450 Activities and Directly Targets CYP2C9. Drug Metab Dispos. 43(6):884-8, 2015
  • Klein M, Thomas M, Hofmann U, Seehofer D, Damm G, Zanger UM. A systematic comparison of the impact of inflammatory signaling on absorption, distribution, metabolism, and excretion gene expression and activity in primary human hepatocytes and HepaRG cells. Drug Metab Dispos. 43(2):273-83, 2015.
Major Networks and Collaborations
  • Virtual Liver (http://www.virtual-liver.de/) German Network for systems biology of the liver
  • FP7 Marie Curie Initial Training Network (ITN) FightingDrugFailure (http://www.fightingdrugfailure.net/)
  • Prof. Andreas Nüssler, Technical University of Munich (human liver bank, hepatocytes)
  • Prof. Andreas Zell, Centre for Bioinformatics Tübingen (bioinformatics, modeling)
Extramural Funding
  • BMBF (Federal Ministry of Education and Research), HepatoSys and Virtual Liver Networks for systems biology of the liver
  • EU FP7 Marie Curie Initial Training Network (ITN) FightingDrugFailure.

Curriculum Vitae Ulrich Zanger, PhD

Affiliation
Professor (apl.) of Biochemical Pharmacology, University of Tübingen Medical School
Deputy Head of the Institute and Section Head Molecular and Cell Biology

Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology
Auerbachstr. 112
D - 70376 Stuttgart Germany
phone: ++49-711-8101 3704
fax: ++49-711-859295
email: uli.zanger@ikp-stuttgart.de
Education and Professional Career
1974-1981 Study of chemistry (diploma), Albert-Ludwigs-University Freiburg i.Br., Germany
1982-1984 Study of preclinical medicine with Physikum examination, Albert-Ludwigs-University Freiburg i.Br., Medical School, Germany
1984-1988 Dissertation, Biocenter of University of Basel, Dept. of Pharmacology (Urs A. Meyer), on biochemistry of cytochrome P450
1988 Dr. phil.nat. (Ph.D.) in biochemistry, University of Basel, Switzerland, Faculty of Natural Science
1989-1991 Postdocteral training, Southwestern Medical Center, Dallas, TX, USA (Michael R. Waterman); work on transcriptional regulation of adrenal steroid hydroxylases
1992-1994 Independent postdoc position at the Biocenter, University of Basel
1994 Senior research scientist at the Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart
1995 Head of Molecular and Cell Biology department at the IKP
2001 Habilitation and Venia Legendi in Biochemical Pharmacology, University of Tübingen Medical School
2004 Member of the scientific board of the Robert-Bosch Hospital and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology
2008 Deputy head of the Institute; extraordinary professorship at the University of Tübingen Medical School
Professional Memberships
German Association of Pharmacology and Toxicology (DGPT)
International Society for the Study of Xenobiotics (ISSX)
American Society for Pharmacology and Experimental Therapeutics (ASPET)
European Society of Pharmacogenomics and Personalised Therapy (ESPT)
Scientific Journal Editorial Board Memberships
Frontiers in Pharmacogenetics, Frontiers in Genetics (Section editor for Pharmacogenetics & Pharmacogenomics)
Associate Editor, Pharmacogenomics
Associate Editor, Drug Metabolism and Personalized Therapy