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Clinical Pharmacogenomics and Cancer

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, metabolomics) 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
  • Pharmacogenomics / Epigenetics of drug metabolizing enzymes, drug transporters and nuclear receptors  
  • Pharmacogenomics of anticancer and immunosuppressive drugs
  • Drug Interaction
  • Pediatric clinical pharmacology
  • Novel methodologies in genomic research and molecular diagnostics
    Prof. Dr. Matthias Schwab

    phone: ++49-711-8101 3700

    Selected References
    Original Articles
    • 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.
    Selected Reviews
     
    • Emami Riedmaier A, Nies AT, Schaeffeler E, Schwab M. Organic Anion Transporters and their Implications in Pharmacotherapy. Pharmacol Rev 2012; 64(3):421-49
    • Nies AT, Koepsell H, Damme K, Schwab M. Organic cation transporters (OCTs, MATEs), in vitro and in vivo evidence for the importance in drug therapy. In: Fromm MF, Kim RB (eds.) Drug transporters - importance for drug disposition and effects. Handbook of Experimental Pharmacology. Springer 2011; 201:105-167
    • 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
    • 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
    Book Editor
    • Schwab M, Kaschka WP, Spina E (eds.). Pharmacogenomics in Psychiatry. Advances in Biological Psychiatry. Vol. 25. Karger, 2010
    • Seyberth WH, Rane A, Schwab M (eds.). Handbook of Experimental Pharmacology. Pediatric Clinical Pharmacology, 14th Edition, Springer, 2011

      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
      Adjunct Professor for "Clinical Pharmacology" and "Biochemistry" at Yerevan State Medical University, Armenia

      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 and later as senior house officer at the Children's Hospital, Nuernberg, 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)
        Special qualification as emergency physician for newborns (acc to DÖGNPI), education for paediatric nephrology, additional certification in: Paediatric ultrasonography of the thyroid gland of head and neck, of the gastrointestinal tract and of female genitals, certification in addiction medicine in children and adolescents, certification in radiological diagnostics for thoracic organs, certification in basic psychosomatic medicine
       1996 Board Certification: Paediatrics and Adolescent Medicine
       2000 Board Certification: Clinical Pharmacology
       2000 - 2005 Coordinator of the research focus "Pharmacogenetics" at the Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany (Prof. Dr. M. Eichelbaum)
       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 Offer as Full Professor and Chair for Clinical Pharmacology, Medical University Innsbruck, Austria
       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

       2010

      Offer as Full Professor and Chair for Clinical Pharmacology, Karolinska University, Sweden in combination with a clinical position as Senior Physician at Karolinska University Hospital

       2015-present

      Coopted Professor at the faculty of mathematics and natural sciences - department of pharmacy and biochemistry, University of Tuebingen

      Appointments and Elected Offices
      • Academy of Science and Literature Mainz, Germany Commission for Medical Research (2014-present, chair since 2015)
      • Baden-Wuerttemberg-International, Germany Elected Committee for the joint partnership between BW and Kanagawa (Japan) “Technologies in an aging society”, Yokohama (2015)
      • European Assocation of Clinical Pharmacology and Therapy (EACPT) Council of EACPT (2010-present, re-election 2015) Executive Committee (2010-present, re-election 2015)
      • European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) EFLM-ESPT working group on Personalized Laboratory Medicine (WG-PLM) (2012-present)
      • European Health Foundation (EHF) Board of Trustees (2013-present)
      • European Medicines Agency (EMEA) CPMP Pediatric Expert Group (PEG): Extraordinary member (2001-2004)
      • German Federal Institute of Drugs and Medicinal Products (BfArM) Expert Group "Drugs for Children and Adolescents" according to AMG (2004-present, re-calls in 2006, 2009, 2011 and 2013): Full Member and Vice Chair
      • German Medical Association (AkdÄ) Drug Commission (2007-present)
      • German Morbus Crohn/Colitis Ulcerosa Association DCCV e.V. Scientific Advisory Board (2014-present)
      • German Society of Child and Adolescent Medicine Committee of Drug Safety (1998-present)
      • German Society of Clinical Pharmacology (DGKliPha) Chair (2013-2018, re-election 2015)
      • German Society of Experimental and Clinical Pharmacology and Toxicology (DGPT) President (2015)
      • Institute of Digital Medicine (IDM Foundation) Stuttgart Executive Board (2011-2013) Board of trustees (2013-present)
      • Interfaculty Centre of Pharmacogenomics and Drug Research (ICEPHA), Tübingen-Stuttgart Scientific Board and Vice Chair (2006-present)
      • International Union of Basic and Clinical Pharmacology (IUPHAR) Div. Clinical Pharmacology/Sub-Committee Pharmacogenetics (2008-present) Drug Metabolism and Transporter Section Executive Board (2010-2014 Councillor, 2014-2018 Vice Chair, since 2018 Chair)
      • Medical Chamber of the State Baden-Württemberg Ethical committee (2004-present) Widerspruchsausschuss postgraduate training (2015-2019)
      • Natural and Medical Sciences Institute (NMI), non-profit public-law foundation, Reutlingen, Germany Deputy Chairman (2010-present)
      • Robert Bosch Stiftung, Stuttgart, Germany, Selection Committee "Fast Track - Exzellenz und Führungskompetenz für Wissenschaftlerinnen auf der Überholspur" (2011,2015,2017)
      • University of Helsinki, International Evaluation Board of the Election of the Erkko Professorship (2014
      • Verbund Klinische Pharmakologie in Deutschland e.V., Chair of the 17th and 18th Annual Meeting 2016 and 2017
      • Vienna Science and Technology Fund, Vienna, Austria, International Evaluation Board of Life Sciences Call 2016 Personalized Medicine (2015-2016)
      Institutional Committees
      Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart and Robert-Bosch-Hospital, Stuttgart, Germany
      • Board of Scientists (1999-2005), Chair (2007- present)
      • Medical Executive Board (2007-present)

      Eberhard Karls University Tuebingen, Germany

      • Committee for Research Strategy & Coordination, Rektorat University Tübingen (2012-present)
      • Board of Members of the Comprehensive Cancer Center (CCC) University Hospital Tübingen (2009-present)
      • Council of the Medical Faculty University Tübingen (2010-present)
      • Extended Research Committee Med. Faculty University Tübingen (2008-present)

      Community Service

      • Committee for qualification as medical specialist in clinical pharmacology, Regional Medical Chamber Nordwürttemberg (2013-present)

      Public (regional, federal) appointments
      Federal German Ministry of Health, Berlin

      • Gendiagnostikkommission (2010-2013)
      • Committee of Experts on Drug Prescription (2013-2017)

      Other appointments and Advisory boards

      • Scientific Advisory Board, Reference Institute for Bioanalytics (Foundation for Pathobiochemistry and Molecular Diagnostics), Bonn (2014-present)
      • Expert Group "HEXAL-Iinitiative drugs for children" (2004-2010)
      • Initiative Medicines for Children e.V. (IKAM) (2012-present)
      Awards and Honors
      • Adjunct Professor for "Clinical Pharmacology" and "Biochemistry" at Yerevan State Medical University, Armenia (2018)
      • Thomson Reuters Highly Cited Researchers, rubric “Pharmacology and Toxicology” (2015/2016)
      • Robert-Pfleger Research Award (2016)
      • Conferment of the “Staufer-Medal” by the Prime Minister of Baden Württemberg (2015)
      • Celebratory Speech ("Vom Wert der Arznei - Wege zu einer zielgerichteten Therapie") at the Annual Meeting of the Academy of Science and Literature, Mainz, Germany (2014)
      • Member of the German National Academy of Sciences ‘Leopoldina’ (2014)
      • Most cited German pharmacologist in Europe (LabTimes, 2013)
      • Member of Faculty of 1000 Prime, Section Pharmacogenomics (2012-2016)
      • Full Member of the Academy of Science and Literature, Mainz, Germany (2012)
      • Authorization of IKP (M. Schwab) as a training center for ‘Drug information’ by the Chamber of Pharmacists of the State Baden-Württemberg (2010)
      • EACPT Key lecture “Personalized Medicine beyond Pharmacogenetics”, 16th World Congress on Basic and Clinical Pharmacology, Copenhagen, Denmark (2010)
      • Most cited pharmacologist in German-speaking countries (Laborjournal, 2009)
      • Galenus von Pergamon Award (2005)
      • Friedrich Hartmut Dost Award (2004)
      • Scholarship according to the "Bayerischen Begabtenförderungsgesetz" (1983-1990)
      Scientific Journal Editorial Board Memberships
      Editor in Chief
      • Pharmacogenetics & Genomics


      Section Editor

      • "Pharmacogenomics and Personalized Medicine" of Genome Medicine


      Editorial Boards

      • British Journal of Clinical Pharmacology, Member of the International Editorial Board (2013-present)
      • Clinical Chemistry (2008-2014)
      • Therapeutic Drug Monitoring
      • Monatsschrift Kinderheilkunde, Section Editor „Drug Therapy” (2015- )
      • Journal of Personalized Medicine
      • Biomedicine Hub


      Book Editor

      • Schwab M, Kaschka WP, Spina E (eds.). Pharmacogenomics in Psychiatry. Advances in Biological Psychiatry. Vol. 25. Karger, 2010
      • Seyberth WH, Rane A, Schwab M (eds.). Handbook of Experimental Pharmacology. Pediatric Clinical Pharmacology, 14th Edition, Springer, 2011


       

      Member of National and International Research Consortia
      • DFG KFO 274 Thrombozyten - Molekulare Mechanismen und translationale Bedeutung, University of Tuebingen, Germany
      • DFG German-African Cooperation Projects in Infectious diseases, University Hospital Tuebingen, Germany
      • GANI_MED (Greifswald Approach to Individualized Medicine), German Federal Ministry for Education and Research (BMBF)
      • German Center for Infection and Research (Dt. Zentrum für Infektionsforschung, IZF)
      • German Consortium for Translational Cancer Research (Dt. Konsortium für Translationale Krebsforschung, DKTK)
      • International Clinical Pharmacogenetics Implementation Consortium (Member, USA)
      • International Clopidogrel Consortium (Member of Steering Committee, Baltimore, USA)
      • International PGx nomenclature working group (USA- Centers for Disease Control and Prevention)
      • International TPMT nomenclature committee (http://www.imh.liu.se/tpmtalleles?l=en)
      • Kinacept consortium: Novel anti-inflammatory compounds for autoimmune diseases (FP7-SME-1)
      • NeuRoSIS-Consortium: Efficacy and Safety of Inhaled Budesonide in very Preterm Infants at risk for Bronchiopulmonary Dysplasia (FP5 Health 2009)
      • PREDICT: Holistic Multi-Scale Modeling of Targeted Protein Therapeutics Action: Towards Predicting Effective Treatment of Cancer (BMBF)
      • SFB 685 “Immunotherapy: Molecular Basis and Clinical Application”, University of Tuebingen, Germany
      • U-PGx consortium: Making actionable pharmacogenomics data and effective treatment optimization accessible to every European citizen“(EU, Horizon 2020)
      • Verbundprojekt FORSYS-Kooperation „Ein systembiologischer Ansatz zur prädiktiven Krebstherapie“ (BMBF)
      • Verbundprojekt INFORM „Individualized Therapy for Relapsed Malignancies in Childhood“, Deutsche Krebshilfe e.V. (Deutsche Kinderkrebsstiftung, DKTK)
      • Virtual Liver Network (BMBF)
      Coordinator of Training Site and Research Networks
      • EU FP7-People-ITN: Marie Curie Initial Training Network “Fighting Drug´Failure”. Lead Applicant and Consortium heads: Schwab M & Brauch H
      • U-PGx consortium: Making actionable pharmacogenomics data and effective treatment optimization accessible to every European citizen“(EU, Horizon 2020, M. Schwab, Vice Chair)
      • BMBF (01ZP0502): Open label, prospective, observational, multi-centre trial in postmenopausal, hormonereceptor positive breast cancer patients treated with either tamoxifen or an aromatase inhibitor (IKP211). Study PI (since 2007)
      • ICEPHA Minigraduate College Membrane associated drug targets in Oncology
      • BMBF Verbundprojekt “Genotype and phenotype guided supplementation of TAMoxifen standard therapy with ENDOXifen in breast cancer patients (TAMENDOX)
      Membership of Professional Bodies
      • International Society of the Study of Xenobiotics (ISSX)
      • American Society for Clinical Pharmacology and Therapeutics (ASCPT)
      • European Society for Developmental, Perinatal & Pediatric • Pharmacology (ESDP)
      • German Society of Clinical and Experimental Pharmacology (DGPT)
      • German Society of Child and Adolescent Medicine (DGKJ)
      • German Society of Nephrology (GPN)
      Reviewing Activities with Journals
      Aliment Pharmacol Ther
      Am J Human Genet
      Ann Intern Med
      Anticancer Drugs
      Basic & Clin Pharmacol & Toxicol
      Biol Neonate
      Biochem Pharmacol
      Blood
      Breast Cancer Res Ther
      Br J Clin Pharmacol
      Br J Pharmacol
      Br Med J
      Cancer Res
      Clin Chemistry
      Clin Cancer Res
      Clin Pharmacol Therapeut
      Clin Pharmacokinet
      Diabetes
      Diabetologica
      Drug Metab Dis
      Eur J Clin Pharmacol
      Eur J Human Genet
      Expert Opin Drug Safety
      Gastroenterology
      Genes and Immunity
      Gut
      Human Mutat
      Human Mol Genet
      Inflam Bowel Dis
      Int J Cancer
      Intervent Cardiol
      JAMA
      J Am Soc Nephrol
      J Clin Oncol
      J Clin Pharmacol
      J Hepatol
      J Natl Cancer Institute
      J Pharmacol Exp Ther
      Lancet Oncol
      Leukemia
      Mol Pharmacol
      Nature
      Nature Genet
      N Engl J Med
      Oncogene
      Pediatrics
      Pediatr Nephrol
      Pharmacogenetics and Genomics Pharmacogenomics
      Pharmacogenomic J
      Placenta
      PNAS
      The Lancet
      Therapeut Drug Monitor
      Xenobiotica
      Technicians

         Monika Elbl


       
       

         Heidi Köhler