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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
Prof. Dr. Ulrich Zanger

phone: ++49-711-8101 3704

Selected References
  • Tremmel R, Klein K, Battke F, Fehr S, Winter S, Scheurenbrand T, Schaeffeler E, Biskup S, Schwab M, Zanger UM (2020): Copy number variation profiling in pharmacogenes using panel-based exome resequencing and correlation to human liver expression. Hum Genet. 139(2):137-49.
  • Tremmel R, Herrmann K, Engst W, Meinl W, Klein K, Glatt H, Zanger UM. (2017): Methyleugenol DNA adducts in human liver are associated with SULT1A1 copy number variations and expression levels. Arch Toxicol. 91(10):3329-39
  • Kandel BA, Thomas M, Winter S, Damm G, Seehofer D, Burk O, Schwab M, Zanger UM (2016): Genome wide comparison of the inducible transcriptomes of nuclear receptors CAR, PXR and PPARα in primary human hepatocytes. Biochim Biophys Acta Gene Gene Regulatory Mechanisms 1859(9):1218-27
  • Tremmel R, Klein K, Winter S, Schaeffeler E, Zanger UM (2016): Gene copy number variation analysis reveals dosage-insensitive expression of CYP2E1. Pharmacogenomics J. 16(6):551-58.
  • Meulendijks D, Henricks LM, Sonke GS, Deenen MJ, Froehlich TK, Amstutz U, Largiadèr CR, Jennings BA, Marinaki AM, Sanderson JD, Kleibl Z, Kleiblova P, Schwab M, Zanger UM et al. (2015): Clinical relevance of DPYD variants c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity: a systematic review and meta-analysis of individual patient data. Lancet Oncol. 16:1639-50
Selected Reviews
  • Zanger UM, Klein K, Kugler N, Petrikat T, Ryu CS (2018): Epigenetics and MicroRNAs in Pharmacogenetics. Adv Pharmacol. 83:33–64.
  • Zanger UM, Klein K, Thomas M, Rieger JK, Tremmel R, Kandel BA, Klein M, Magdy T (2014): Genetics, epigenetics, and regulation of drug-metabolizing cytochrome p450 enzymes. Clin Pharmacol Ther. 95(3):258-61.
  • Zanger UM, Schwab M (2013): Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 138(1):103-41.
  • Meyer UA, Zanger UM, Schwab M (2013): Omics and drug response. Annu Rev Pharmacol Toxicol. 53, 475-502.
Book Editor
  • P. Anzenbacher and U.M. Zanger (Eds): Metabolism of Drugs and other Xenobiotics. Wiley-VCH, Weinheim 2012, 724 pages
Major Networks and Collaborations
  • PPAP "Polycyclic Polyprenylated Acylphloroglucinols, a promising class of antibiotics to treat infections caused by multi-resistant bacteria": National Research network including universities of Dresden, Stuttgart, Tübingen, Ulm.
  • FUSAFE-2: International Research Network on 5-Fluorouracil toxicity including universities of Nice (France), Utrecht (Netherlands), Birmingham (UK), Bern (Switzerland) and others.
Extramural Funding
  • FUSafe-2 “Search for a multigene signature to secure fluoropyrimidine-based chemotherapies in colorectal cancer patients" Coordinator: Marie Christine Etienne-Grimaldi, University of Nice, France (2019-2021)
  • BMBF (Federal Ministry of Education and Research), HepatoSys and Virtual Liver Networks for systems biology of the liver (2010-2014)
  • EU FP7 Marie Curie Initial Training Network (ITN) "FightingDrugFailure" Coordinator: Hiltrud Brauch (2009-2013)
Awards and Honors
  • 2020 ISSX European Scientific Achievement Award
  • Keynote Lecture 2nd Latin American Congress of Pharmacogenomics and Personalized Medicine, Durango, Mexico (Oct. 2017)
  • Distinguished Lecture, 32nd JSSX Congress, Tokyo, Japan (Nov. 2017)
  • Thomson Reuters Highly Cited Researcher, rubric “Pharmacology and Toxicology” (2014 and 2015)
  • Postdoctoral Scholarship Award, Boehringer Ingelheim Fonds, Mainz, Germany (1989)
Academic Activities
  • Member of the Microsomes and Drug Oxidations International Advisory Board
  • Chair of the Organizing Committee of the 20th International Symposium on Microsomes and Drug Oxidations, Stuttgart, May 18-22, 2014
  • Member of the Scientific Board of the Robert-Bosch Hospital and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology
  • Peer Reviewer for >30 life science journals
  • Reviewer of grant proposals (German Research Foundation, Swiss Research Foundation and others)
  • Teaching in toxicology and pharmacology at the University of Tübingen Medical School
  • Graduate Student Training as Thesis Advisor, Reviewer, and Dissertation Committee Member for Universities of Tübingen, Stuttgart, Basel, Lausanne, Brisbane and others

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
2014-2015 Visiting Professor, Kyushu University, Department of Molecular Biology, Faculty of Medical Sciences, Fukuoka, Japan
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
Associate Editor, Frontiers in Pharmacogenetics, Frontiers in Genetics
Associate Editor, Pharmacogenomics
Associate Editor, Drug Metabolism and Personalized Therapy