Professor Roland Wolf OBE

Professor of Pharmacology

Defining the pathways which are associated with individual responses and efficacy of anticancer drugs

Address:

School of Medcine
Division of Cancer Research
Jacqui Wood Cancer Centre
University of Dundee
James Arrott Drive
Ninewells Hospital And Medical School
Dundee
DD1 9SY

Phone Number:

+(44) 01382 383134

Email Address:

c.r.wolf@dundee.ac.uk

Biography

Professor Wolf’s research focuses on defining the pathways that determine individual sensitivity to drugs and environmental chemicals.  These pathways play a key role in disease susceptibility and in the outcome of drug therapy.  Research in this area has provided one of the fundamental cornerstones in the development of the concept of stratified/personalised treatment of diseases such as cancer.  After working in West Germany, USA and England, Professor Wolf headed the research labs in the Imperial Cancer Research Fund’s Medical Oncology Unit at the Western General Hospital in Edinburgh and subsequently led the ICRF Molecular Pharmacology group in the Biochemistry Department there.  In 1992 Professor Wolf relocated to Dundee to establish the Biomedical Research Centre, subsequently the Biomedical Research Institute.  Following a period as Director of the Medical Research Institute he is currently the Director of Strategic Development. Professor Wolf’s research has involved numerous academic collaborations as well as close collaborations with a wide range of pharmaceutical companies.  In 2001 he founded the biotechnology company, CXR Biosciences, which provides pre-clinical drug development and chemical safety services to third parties, as well as having its own in-house drug discovery and development programme.  He left CXR in 2012.  Professor Roland Wolf was rewarded for his services to science with an OBE in the New Year’s Honours list in 2010.

Research

Research

Professor Wolf’s research work has focused on molecular, genetic, biochemical and pharmacological studies into the pathways that have evolved to combat our exposure to environmental chemicals and oxidative stress.  These pathways play a pivotal role in disease aetiology and in defining the outcome of drug treatment.  His research work has encompassed a wide range of experimental approaches, including defining genetic variation in the expression of these genes and their association with disease susceptibility and therapeutic outcome, defining the structures of the proteins involved, particularly the cytochrome P450-dependent mono-oxygenase system, to molecular, genetic and pharmacological studies using transgenic models.  In recent times the development and application of transgenic approaches has been the research focus of his group, where a wide range of genes involved in drug metabolism and pathways of chemical toxicity have been either deleted or humanised.  In addition, a range of reporter systems which allow  in vivo toxicological and environmental responses to be measured , particularly those which measure oxidative stress , DNA damage and inflammation.  These models are currently being used to understand the role of oxidative stress, for example, in degenerative disease and in cancer.  A further major component of Professor Wolf’s research is the application of mouse models that have been humanised for pathways of drug disposition to understand the role of metabolism and pharmacodynamics as a determinant in the outcome of cancer chemotherapy.  The long-term goal of these studies is to understand the relationship between drug levels and patient outcome so that treatments in the future can be correctly administered and stratified.  This work is currently funded by Cancer Research UK, the MRC and the European Union.

 

Publications

Recent Publications:

Henderson, C.J , Cameron, A.R.,., Chatham, L., Stanley, L.A and Wolf, C.R. Evidence that the capacity of non-genotoxic carcinogens to induce oxidative stress is subject to marked variability. Tox. Sci. (2015 in Press)

Henderson, C.J., McLaughlin, Scheer, N., Stanley, L.A., Wolf, C.R. Cytochrome b5 is a major detrerminant of human cytochrome P450 CYP3A4 and CYP2D6 activity in vivo.  Molecular Pharmacology  87 733-9 (2015).

Henderson, C.J., McLaughlin, L.A., McLaren, A.W., Wolf, C.R. A novel aryl receptor-Cre recombinase system applied to the conditional deletion of cytrochrome P450 oxidoreductase in mouse tissues. Biochem J. 465, 479-88 (2015).

Henderson, C., McLaren, A., Wolf, C.R. In vivo regulation of human glutathione transferase GSTP by chemopeventitive agents. Cancer Research 74, 4378-4387(2014).

Henderson, C.J., McLaughlin, L.A., and Wolf, C.R.  Evidence that cytochrome b5 and cytochrome b5 reductase can act as sole electron donors to the hepatic cytochrome P450 system.  Mol. Pharmacol. 83, 1209-1217 (2013).

Scheer, N. and Wolf, C.R. Genetically humanized mouse models of drug metabolizing enzymes and transporters and their applications. Xenobiotica 2, 96-108 (2013).

Scheer, N., Kapelyukh, Y., Chatham, L., Rode, A., Buechel, S. and Wolf, C.R.  Generation and characterization of novel cytochrome P450 Cyp2c gene cluster knockout and CYP2C9 humanized mouse lines.  Mol. Pharmacol. doi: 10.1124/mol.112.080036 (2012). 

Smith, G., Ng, M.T.H., Shepherd, L., Herrington, C.S., Gourley, C., Ferguson, M.J. and Wolf, C.R.  Individuality in FGF1 expression significantly influences platinum resistance and progression free survival in ovarian cancer. Br. J. Cancer doi: 10.1038/bjc.2012.410 (2012). 

Scheer, N., Kapelyukh, Y., McEwan, J., Beuger, V., Stanley, L.A., Rode, A. and Wolf, C.R. Modelling human cytochrome P450 2D6 metabolism and drug-drug interaction by a novel panel of knockout and humanized mouse lines. Mol. Pharmacol. 81, 63-72 (2011). 

Henderson, C.J., Ritchie, K.J. (joint 1st authors), McLaren, A., Chakravarty, P. and Wolf, C.R. Increased skin papilloma formation in mice lacking glutathione S-transferase GSTP.  Cancer Res. 71,7048-7060 (2011). 

Henderson, C.J. and Wolf, C.R.  Knockout and transgenic mice in glutathione transferase research. Drug Metab. Rev. 43, 152-164 (2011). 

Hasegawa, M., Kapelyukh, Y., Tahara, H., Seibler, J., Rode, A., Krueger, S., Lee, D.N, Wolf, C.R. and Scheer, N.1 (1joint senior authors.) Quantitative prediction of human pregnane X receptor and cytochrome P450 3A4 mediated drug-drug interaction in a novel multiple humanized mouse line. Mol. Pharmacol. 80, 518-528 (2011). 

McLaughlin, L.A., Ronseaux, S., Finn, R.D., Henderson, C.J. and Wolf, C.R.  Deletion of microsomal cytochrome b5 profoundly affects hepatic and extra-hepatic drug metabolism.  Mol. Pharmacol. 78, 269-278 (2010). 

Ritchie, K.J., Walsh, S., Sansom, O.J., Henderson, C.J. and Wolf, C.R.  Markedly enhanced colon tumorigenesis in Apc min mice lacking glutathione S-transferase Pi.  Proc. Natl. Acad. Sci USA 106, 20859-64 (2009). 

Henderson, C.J., Scheer, N. and Wolf, C.R.  Advances in the generation of mouse models to elucidate the pathways of drug metabolism in rodents and man.  Expert Rev. Clin. Pharmacol. 2,105-109 (2009). 

Finn, R.D., Henderson, C.J., Scott, C.L. and Wolf, C.R. Unsaturated fatty acid regulation of cytochrome P450 expression via a CAR-dependent pathway.  Biochem J., 417, 43-54 (2008). 

Finn, R.D., McLaughlin, L.A., Ronseaux, S., Rosewell, I., Houston, J.B., Henderson, C.J. and Wolf, C.R.  Defining the in vivo role for cytochrome b5 in cytochrome P450 function through the conditional hepatic deletion of microsomal cytochrome b5. J. Biol. Chem. 283, 31385-31393 (2008). 

Wang, X. J., Hayes, J.D., Henderson, C.J. and Wolf, C.R.  Identification of retinoic acid as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha.  Proc. Natl. Acad. Sci. USA 104, 19589-19594 (2007). 

Ritchie, K.J., Henderson, C.J., Wang, X. J., Vassieva, O., Carrie, D., Farmer, P.B., Gaskell, M., Park, K. and Wolf, C.R.  Glutathione transferase Pi plays a critical role in the development of lung carcinogenesis following exposure to tobacco-related carcinogens and urethane.  Cancer Res. 67,9248-9257 (2007). 

Finn, R.D., McLaren, A.W., Carrie, D., Henderson, C.J. and Wolf, C.R.  Conditional deletion of cytochrome P450 oxidoreductase in the liver and gastrointestinal tract: a new model for studying the functions of the P450 system.  J. Pharmacol. Exp. Ther. 322, 40-47 (2007). 

Wang, X.J., Hayes, J.D. and Wolf, C.R.  Generation of a stable antioxidant response element-driven reporter gene cell line and its use to demonstrate redox-dependent activation of Nrf2 (NF-E2 p45-related factor 2) by cancer chemotherapeutic agents.  Cancer Res. 22, 10983-10994 (2006).

PhD Supervision

CRW has supervised /co supervised 46 PhD students

Conferences

2014:

20th International Symposium on Microsomes & Drug Oxidations, Germany

The Drug Metabolism Gordon Research Conference, Holderness, NH, USA

EUROTOX 2014, Edinburgh

International Symposium on Methods for Studying Drug Metabolism and Transport and Herbal Derived Medicines (METHODS 2014) Cape Town, South Africa

1st Emerging Industry Forum (EIF-2014),Dalian, China

19th World Congress on Advances in Oncology & 17th International Symposium on Molecular Medicine, Athens, Greece

3rd International Conference on Tissue Science and Regenerative Medicine, Valencia,

Spain

35th Annual ACT Meeting, Orlando, Florida, USA

2015:

ASPET Boston  USA,

International Conference on Pharmaceutical Sciences, Dubai, UAE

European ISSX Meeting Glasgow, UK

Retirement Symposium Herman Autrup, Denmark

International Symposium on Methods for Studying Drug Metabolism and Transport and Herbal Derived Medicines (METHODS 2015) Cape Town, South Africa