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Pharmacogenetics/genomics of ADME Genes in Human Liver

ADME-genes are genes involved in the absorption, distribution, metabolism and/or excretion of foreign (xenobiotic) and endogenous substances, including most clinically and recreationally used drugs, plant toxins, environmental chemicals, as well as steroid hormones, bile acids, and many other endogenous metabolites and signalling molecules. ADME genes often are highly variably expressed (>100fold) interindividually which can lead to unpredictable drug response, toxicity or cancer. Factors that cause variability include sex, hormonal status, circadian rhythm, environmental exposure, or genetic polymorphisms. Most of the important genes have been investigated for SNPs and their impact on expression or drug treatment outcome. Purpose of this project is to find new factors or candidates contributing to the variable expression of genes in the ADME group. 
 
Major Projects
  • Tissue “Biobank”:Liver
  • Pharmacogenomics of CYP3A4 and CYP1A2 
  • Pharmacogenetics of CYP2B6
  • Genomewide analysis of Polymorphisms and Gene Expression in Human Liver
  • Systems Biology of the Liver (BMBF)
Dr. Kathrin Klein

phone: ++49-711-8101 3706

Selected References
  • Tremmel, R. et al. Methyleugenol DNA adducts in human liver are associated with SULT1A1 copy number variations and expression levels. Archives of toxicology (2017). doi: 10.1007/s00204-017-1955-4.
  • Radloff R, Gras A, Zanger UM, Masquelier C, Arumugam K, Karasi J-C, et al. Novel CYP2B6 Enzyme Variants in a Rwandese Population: Functional Characterization and Assessment of In Silico Prediction Tools. Hum. Mutat. (2013); 34:725–34. doi:10.1002/humu.22295.
  • Klein K, Thomas M, Winter S, Nussler AK, Niemi M, Schwab M, Zanger UM.: PPARA: A Novel Genetic Determinant of CYP3A4 In Vitro and In Vivo. Clinical Pharmacology & Therapeutics (2012); 91:1044. doi:10.1038/clpt.2011.336
  • Riedmaier, S, K.Klein, U.Hofmann, JE Keskitalo, PJ Neuvonen, M.Schwab, M.Niemi,and UM Zanger. UDP-Glucuronosyltransferase (UGT) Polymorphisms Affect Atorvastatin Lactonization In Vitro and In Vivo. Clinical Pharmacology & Therapeutics (2010); 87(1):65-73
  • Klein, K., S. Tatzel, S. Raimundo,T. Saussele, E. Hustert, J. Pleiss, M. Eichelbaum, U. M. Zanger. A Natural Variant of the Heme-Binding Signature (R441C) Resulting in Complete Loss of Function of CYP2D6. Drug Metabolism and Disposition (2007); 35(8):1247-1250
  • Saussele, T., O. Burk, J. K. Blievernicht, K. Klein, A. Nussler, N. Nussler, J. G. Hengstler, M. Eichelbaum, M. Schwab, and U. M. Zanger. Selective induction of human hepatic cytochromes P450 2B6 and 3A4 by metamizole. Clin Pharmacol Ther (2007); 82:265-274.
  • Klein, K., T. Lang, T. Saussele, E. Barbosa-Sicard, W. H. Schunck, M. Eichelbaum, M. Schwab, and U. M. Zanger. 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); 15:861-873

Curriculum Vitae Kathrin Klein, PhD

Affiliation
Biologist
Assistant Leader of the Biostatistics/Databases Department
Member of the IKP-Pharmacogenetics group (Zanger)

Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology
Auerbachstr. 112
D-70376 Stuttgart Germany
phone: ++49-711-8101 3706
fax: ++49-711-859295
email: kathrin.klein@ikp-stuttgart.de
Education and Professional Career
1984-1988 Study of Biology at the University of Stuttgart
1989 Diploma Thesis (Institute of Biology, Biophysics department, University Stuttgart) “Zellzyklusanalysen an Monolayerkulturen und Multizellsphäroiden”
1990-1995 PhD (Institute of Industrial Genetics, University Suttgart) “Die Bedeutung von Saccharose-Stoffwechselgenen für die Bakterielle Isomaltulose-Herstellung”
1996-1998 Incentive Program of the Baden-Württemberg Ministry of Education and Science: Südzucker AG / Institute of Industrial Genetics: “Development of genetic methods to optimize the Palatinose yield using Saccharose-Mutase from P.rubrum”
1999 - present Postdoctoral fellow at Institute of Clinical Pharmacology in the Department of Pharmacogenetics
Professional Memberships
Since 2009: Member of International Society for the Study of Xenobiotics (ISSX)
Scientific Journal Editorial Board Memberships
Associate Editor of Frontiers in Pharmocogenetics