Clinical Impact of Pharmacogenomics
Variation in drug disposition and response among patients is a major concern associated with many pharmaceuticals used in all disciplines of medicine. The clinical relevance of variability is most evident with drugs that have a narrow therapeutic window (i.e., the dose used is close to the dose probably resulting in drug-related toxicity in most individuals). With increasingly comprehensive information available from the Human Genome Project Pharmacogenomics aims to identify underlying factors which have profound effects on patient outcome as well as drug toxicity. We are particularly interested in the identifi- cation and elucidation of genetic variants relevant for ADME processes such as drug metabolizing enzymes, drug transporters and nuclear receptors. However, it is unlikely that one single gene will affect exclusively disease and/or treatment outcome, and therefore a more comprehensive approach is required to consider genetics in entire biological/pharmacological pathways. Recently developed ‘-omics appoaches’ (e.g., genomics, transcriptomics, proteomics) will be helpful to identify further putative targets for better prediction of drug response and will complement each other. Microarray technologies (e.g. cDNA arrays, GWA) have shown to be helpful for identifying novel susceptibility genes, redefining disease diagnosis and predicting therapy response to specific drugs. Additional information on the epigenetic level (e.g. methylation, miRNA) needs consideration.
Major Projects
- ADME Pharmacogenomics
- Pharmacogenomics of anticancer and immunosuppressive agents
- Drug - Drug Interaction
- Pediatric clinical pharmacology
- Novel methodologies in genomic research
Prof. Dr. Matthias Schwab
phone: ++49-711-8101 3700
Selected References
Original Articles
Selected Reviews
- Stanulla M, Schaeffeler E, Möricke A, Coulthard SA, Cario G, Schrauder A, Kaatsch P, Dördelmann M, Welte K, Zimmermann M, Reiter A, Eichelbaum M, Riehm H, Schrappe M, Schwab M. Thiopurine methyltransferase genetics is not a major risk factor for secondary malignant neoplasms after treatment of childhood acute lymphoblastic leukemia on Berlin- Frankfurt-Münster protocols. Blood. 2009; 114:1314-8.
- Schroth W, Goetz MP, Hamann U, Fasching PA, Schmidt M, Winter S, Fritz P, Simon W, Suman VJ, Ames MM, Safgren SL, Kuffel MJ, Ulmer HU, Boländer J, Strick R, Beckmann MW, Koelbl H, Weinshilboum RM, Ingle JN, Eichelbaum M, Schwab M, Brauch H. Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA. 2009; 302:1429-36
- Nies AT, Koepsell H, Winter S, Burk O, Klein K, Kerb R, Zanger UM, Keppler D, Schwab M, Schaeffeler E. Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver. Hepatology. 2009; 50(4):1227-40
- 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; 26:2131-38.
- Stanulla M, Schaeffeler E, Flohr T, Cario G, Schrauder A, Zimmermann M, Welte K, Ludwig WD, Bartram CR, Zanger UM, Eichelbaum M, Schrappe M, Schwab M. Thiopurine methyltransferase (TPMT) genotype and early treatment response to mercaptopurine in childhood acute lymphoblastic leukemia. JAMA. 2005; 293:1485-89
Selected Reviews
- Kerb R, Fux R, Mörike K, Kremsner PG, Gil JP, Gleiter CH, Schwab M. Pharmacogenetics of antimalarial drugs: effect on metabolism and transport. Lancet Infect Dis 2009;9(12):760-74
- Nies AT, Schwab M, Keppler D: Interplay of conjugating enzymes with OATP uptake transporters and ABCC/MRP efflux pumps in the elimination of drugs. Exp Opin Drug Metab Toxicol 2008;4(5):545-568,
- Kirchheiner J, Schwab M: Heterogeneity of Drug Responses and Individualization of Therapy (Chapter 16). In: Waldman & Terzic. Pharmacology and Therapeutics. Principles to Practice. Elsevier, Philadelphia, US 2008, p 225-238
Curriculum Vitae Matthias Schwab, MD
Affiliation
Professor and Chair of Clinical Pharmacology
Head of the Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart
and Department of Clinical Pharmacology, Institute of Experimental and Clinical Pharmacology and Toxicology, University Hospital, Tuebingen
Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology
Auerbachstr. 112
D - 70376 Stuttgart Germany
phone: ++49-711-8101 3700
fax: ++49-711-85 92 95
email: matthias.schwab@ikp-stuttgart.de
Head of the Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart
and Department of Clinical Pharmacology, Institute of Experimental and Clinical Pharmacology and Toxicology, University Hospital, Tuebingen
Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology
Auerbachstr. 112
D - 70376 Stuttgart Germany
phone: ++49-711-8101 3700
fax: ++49-711-85 92 95
email: matthias.schwab@ikp-stuttgart.de
Education and Professional Career
| 1983 - 1990 | Study of medicine, Friedrich-Alexander University of Erlangen-Nuernberg |
| 1990 - 1993 | Civilian service as house officer ad later as senior house officer at the Children's Hospital, Nuernber, Germany (Prof. Dr. H. Gröbe) |
| 1991 | Doctor`s degree of medicine, Institute of Toxicology and Pharmacology, University Erlangen Nuernberg (Prof. Dr. R. Böcker / Prof. Dr. C. Estler). |
| 1992 | State Licence as medical doctor |
| 1993 - 1995 | Senior house officer at the University Hospital of Children and Adolescents, Friedrich-Alexander University of Erlangen-Nuernberg, Erlangen, Germany (Prof. Dr. C. Stehr) |
| 1995 - 2001 | Fellow in clinical pharmacology at the Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany (Prof. Dr. M. Eichelbaum) |
| 1996 | Board Certification: Paediatrics and Adolescent Medicine |
| 2000 | Board Certification: Clinical Pharmacology |
| 2001 - 2005 | Senior physician and Head of the Research Unit for Clinical Trials and Drug Information Centre at the Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany (Prof. Dr. M. Eichelbaum) |
| 2003 |
Habilitation for „Clinical Pharmacology and Paediatric Pharmacology“ at the Eberhard-Karls University Tuebingen |
| 2005 - 2006 | Visiting Professor, St. Jude Children’s Research Hospital, Department of Pharmaceutical Sciences, Memphis, Tennessee, USA (Prof. W.E. Evans) |
| 2006 | Decline of appointment as full professor for Clinical Pharmacology, Medical University Innsbruck, Austria |
| 1/2007 - present |
Professor and Chair of Clinical Pharmacology, Eberhard Karl University Tuebingen, Germany Head of the Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, and the Department of Clinical Pharmacology, Institute of Experimental and Clinical Pharmacology and Toxicology, University Hospital, Tuebingen |
Professional Memberships
1998 - present: Full member of the "Committee of Drug Safety" of the German Society of Child and Adolescent Medicine (Chair: Prof. Dr. Seyberth, Marburg)
1999 – 2005: Member of the Research Committee at the Robert-Bosch Hospital, Stuttgart
2002 - 2004: Full Member of the Expert Group "Drugs for Children and Adolescents" at the German Federal Institute of Drugs and Medicinal products (BfArM)
2004 – present: Member of the Expert Group "HEXAL-Iinitiative drugs for children"
2004 – present: Member of the ethical committee of the Landesärztekammer Baden-Württemberg
2004: Friedrich Hartmut-Dost Award
2005: Galenus von Pergamon Award
2006 - 2009: Full member (2006) and Vice Chair (2008) of the Expert Group "Drugs for Children and Adolescents" at the German Federal Institute of Drugs and Medicinal products (BfArM)
2007 – present: Chairman of the Research Committee at the Robert-Bosch Hospital/IKP, Stuttgart
2007 – present: Member of the „Drug Commission of the German Medical Association (AkdÄ)
2008: Member of IUPHAR Division of Clinical Pharmacology - Sub-Committee Pharmacogenetics
2009: Re-Call: Full member and Vice Chair of the Expert Group "Drugs for Children and Adolescents" according to AMG at the German Federal Institute of Drugs and Medicinal products (BfArM)
2009: Member of the medical executive board of the Robert Bosch Hospital, Stuttgart
2009: Chair - Member of the Comprehensive Cancer Center (CCC) of the University Hospital, Tuebingen
2010: Full member of the American Society for Clinical Pharmacology and Therapeutics (ASCPT)
2010: Vice Chairman of the Natural and Medical Sciences Institute (NMI) in Reutlingen (non-profit public-law foundation)
2010 - 2014: Councillor for the European region in the „IUPHAR Drug Metabolism Section Executive Board“
1999 – 2005: Member of the Research Committee at the Robert-Bosch Hospital, Stuttgart
2002 - 2004: Full Member of the Expert Group "Drugs for Children and Adolescents" at the German Federal Institute of Drugs and Medicinal products (BfArM)
2004 – present: Member of the Expert Group "HEXAL-Iinitiative drugs for children"
2004 – present: Member of the ethical committee of the Landesärztekammer Baden-Württemberg
2004: Friedrich Hartmut-Dost Award
2005: Galenus von Pergamon Award
2006 - 2009: Full member (2006) and Vice Chair (2008) of the Expert Group "Drugs for Children and Adolescents" at the German Federal Institute of Drugs and Medicinal products (BfArM)
2007 – present: Chairman of the Research Committee at the Robert-Bosch Hospital/IKP, Stuttgart
2007 – present: Member of the „Drug Commission of the German Medical Association (AkdÄ)
2008: Member of IUPHAR Division of Clinical Pharmacology - Sub-Committee Pharmacogenetics
2009: Re-Call: Full member and Vice Chair of the Expert Group "Drugs for Children and Adolescents" according to AMG at the German Federal Institute of Drugs and Medicinal products (BfArM)
2009: Member of the medical executive board of the Robert Bosch Hospital, Stuttgart
2009: Chair - Member of the Comprehensive Cancer Center (CCC) of the University Hospital, Tuebingen
2010: Full member of the American Society for Clinical Pharmacology and Therapeutics (ASCPT)
2010: Vice Chairman of the Natural and Medical Sciences Institute (NMI) in Reutlingen (non-profit public-law foundation)
2010 - 2014: Councillor for the European region in the „IUPHAR Drug Metabolism Section Executive Board“
Scientific Journal Editorial Board Memberships
- Editor of “Pharmacogenetics & Genomics”
- Section Editor for “Personalized Medicine and Therapeutics” of Genome Medicine
- Editorial Board Member of "Clinical Chemistry", "Therapeutic Drug Monitoring" and "The Open Clinical Chemistry Journal"
