Membrane Transport Proteins and Pharmacogenomics

Transporters play critical roles in the absorption, disposition, and elimination of numerous drugs that are in clinical use. Alterations in the expression and function of these transporters may significantly contribute to drug pharmacokinetics and the interindividual variability of drug response. Our research aims to unravel genetic and non-genetic factors that affect transporter expression and function. The long-term goal is to explore the impact of transporter Pharmacogenomics in disease cohorts already available at the Institute of Clinical Pharmacology.

Major Projects

Molecular cell biology of drug transporters
Functional characterization of drug transporters
Pharmacogenomics of drug transporters

Prof. Dr. Anne Nies

phone: ++49-711-8101 3729

Anne Nies

Selected References

PubMed Anne T. Nies

Drenberg C, Gibson AA, Pounds S, Shi L, Rhinehart D, Li L, Hu S, Du G, Nies AT, Schwab M, Pabla N, Blum W, Gruber TA, Baker SD, Sparreboom A. OCTN1 is a high-affinity carrier of nucleoside analogs. Cancer Res (2017) Apr 15;77:2102-2111.
Neul C, Schaeffeler E, Sparreboom A, Laufer S, Schwab M, Nies AT. Impact of membrane drug transporters to resistance of small molecule tyrosine kinase inhibitors. Trends Pharmacol Sci (2016);37:904-932
Nies AT, Damme K, Kruck S, Schaeffeler E, Schwab M. Structure and function of multidrug and toxin extrusion proteins (MATEs) and their relevance to drug therapy and personalized medicine. Arch Toxicol (2016);90:1555-1584
Emami Riedmaier A, Burk O, van Eijck BAC, Schaeffeler E, Müller S, Winter S, Zanger UM, Schwab M, Nies AT. Organic anion transporter 7: a novel pravastatin uptake transporter in human liver regulated by hepatocyte nuclear factor 4-alpha. Pharmacogenomics J (2016); 16:341-351.
Arlanov R, Lang T, Jedlitschky G, Schaeffeler E, Ishikawa T, Schwab M, Nies AT. Functional characterization of common protein variants in the efflux transporter ABCC11 and identification of T546M as functionally-damaging variant. Pharmacogenomics J (2016); 16(2):193-201.

Sprowl JA, Ong SS, Gibson AA, Hu S, Du G, Lin W, Li L, Bharil S, Ness RA, Stecula A, Offer SM, Diasio RB, Nies AT, Schwab M, Cavaletti G, Schlatter E, Ciarimboli G, Schellens JHM, Isacoff EY, Sali A, Chen T, Baker SD, Sparreboom A, Navjotsingh P. A phosphotyrosine switch regulates organic cation transporters. Nat Commun (2016) 16;7:10880. FREE ARTICLE

Mooij MG, Nies AT, Knibbe CAJ, Schaeffeler E, Tibboel D, Schwab M, De Wildt SN. Development of human membrane transporters: drug disposition and pharmacogenetics. Clin Pharmacokinet (2016); 55:507-524. FREE ARTICLE

Fisel P, Stühler VR, Winter S, Rausch S, Hennenlotter J, Nies AT, Stenzl A, Scharpf M, Fend F, Kruck S, Bedke J, Schwab M, Schaeffeler E. MCT4 surpasses the prognostic relevance of the ancillary protein CD147 in clear cell renal cell carcinoma. Oncotarget (2015);6:30615-30627. FREE ARTICLE

Nies AT, Magdy T, Schwab M, Zanger UM. Role of ABC transporters in fluoropyrimidine-based chemotherapy response. Adv Cancer Res (2015);125:217-243
Wolking S, Schaeffeler E, Lerche H, Schwab M, Nies AT. Impact of genetic polymorphisms of ABCB1 (MDR1, P-glycoprotein) on drug disposition and potential clinical implications: update of the literature. Clin Pharmacokinet (2015);54:709-735

Emami Riedmaier A, Schaeffeler E, Nies AT, Mörike K, Schwab M. Stratified medicine for the use of anti-diabetics medication in treatment of T2DM and cancer: where do we go from here? J Intern Med (2015);277:235-247. FREE ARTICLE

Namisaki T, Schaeffeler E, Fukui H, Yoshiji H, Nakajima Y, Fritz P, Schwab M, Nies AT. Differential expression of drug uptake and efflux transporters in Japanese patients with hepatocellular carcinoma. Drug Metab Dispos (2014);42:2033-2040. FREE ARTICLE

Nies AT, Schaeffeler E, van der Kuip H, Cascorbi I, Bruhn O, Kneba M, Pott C, Hofmann U, Volk C, Ruth P, Hu S, Baker SD, Sparreboom A, Ruth P, Koepsell H, Schwab M. Cellular uptake of imatinib into leukemic cells is independent of human organic cation transporter 1 (OCT1). Clin Cancer Res (2014);20:985-994. FREE ARTICLE

Fisel P, Kruck S, Winter S, Bedke J, Hennenlotter J, Nies AT, Scharpf M, Fend F, Stenzl A, Schwab M, Schaeffeler E. DNA methylation of the SLC16A3 promoter regulates expression of the human lactate transporter MCT4 in renal cancer with consequences for clinical outcome. Clin Cancer Res (2013);19:5170-5181. FREE ARTICLE

Nies AT, Niemi M, Burk O, Winter S, Zanger UM, Stieger B, Schwab M, Schaeffeler E. Genetics is a major determinant of expression of the human hepatic uptake transporter OATP1B1, but not of OATP1B3 and OATP2B1. Genome Med (2013);5:1. FREE ARTICLE

Emami Riedmaier A, Fisel P, Nies AT, Schaeffeler E, Schwab M. Metformin and cancer: from the old medicine cabinet to pharmacological pitfalls and prospects. Trends Pharmacol Sci (2013);34:126-135

Emami Riedmaier A, Nies AT, Schaeffeler E, Schwab M. Organic anion transporters and their implications in pharmacotherapy. Pharmacol Rev (2012);64:421-449. FREE ARTICLE

Schaeffeler E, Hellerbrand C, Nies AT, Winter S, Kruck S, Hofmann U, van der Kuip H, Zanger UM, Koepsell H, Schwab M. DNA methylation is associated with downregulation of the organic cation transporter OCT1 (SLC22A1) in human hepatocellular carcinoma. Genome Med (2011);3:82. FREE ARTICLE

Nies AT, Hofmann U, Resch C, Schaeffeler E, Rius M, Schwab M. Proton pump inhibitors inhibit metformin uptake by organic cation uptake transporters (OCTs). PLoS ONE (2011);6:e22163. FREE ARTICLE

Nies AT, Koepsell H, Winter S, Burk O, Klein K, Kerb R, Zanger UM, Keppler D, Schwab M, Schaeffeler E (2009) Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SCL22A3) is affected by genetic factors and cholestasis in human liver. Hepatology 50, 1227-1240.

Curriculum Vitae Anne Nies, PhD

Affiliation

Head Membrane Transport Proteins

Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology
Auerbachstrasse 112
70376 Stuttgart Germany
phone: ++49-711-8101 3729
fax: ++49-711-859295
email: anne.nies@ikp-stuttgart.de

Education and Professional Career

1984-1990	Studies of Biology, University of Düsseldorf, Germany
1990	Diploma in Biology, University of Düsseldorf
1990-1993	PhD thesis in Biology, University of Düsseldorf
1993	Dr. rer. nat. (Ph.D.) in Biology, University of Düsseldorf, on transport and metabolism of urate in the hepatopancreas of the lobster
1994-1996	Postdoctoral Research Fellow of the Deutsche Forschungsgemeinschaft at Tufts University, Department of Physiology (Boston, MA, USA), on the biochemistry und molecular biology of P-glycoprotein and other hepatic transport systems
1996-2007	Senior Research Scientist at the German Cancer Research Center, Division of Tumor Biochemistry, Heidelberg, Germany. Research area: Molecular cell biology of ATP-dependent efflux pumps and uptake transporters in the plasma membrane
2004	Habilitation and venia legendi in Biochemistry, University of Heidelberg Medical School
Since 2007	Senior Group Leader and Head of Membrane Transport Proteins, Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
Since 2008	Venia legendi in Biochemical Pharmacology, University of Tübingen Medical School, Germany
2014	Extraordinary professorship at the University of Tübingen Medical School