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Professor Paul Thornalley

Paul J Thornalley

TITLE   


Professor of Systems Biology

CONTACT   


Metabolic & Vascular Health
Warwick Medical School
Clinical Sciences Research Laboratories
CSB, UHCW - Walsgrave
Coventry
CV2 2DX
Tel: +44(0)24 7696 8594
Fax: +44(0)24 7696 8653
Email: P.J.Thornalley@warwick.ac.uk

 


RESEARCH PROFILE


Leading a multi-disciplinary team working in the field of disease mechanisms - particularly the study of damage to the proteome by glycation, oxidation and nitration, related enzymatic countermeasures raised by transcription factor Nrf2 and antioxidant response element (ARE)-regulated expression and other metabolic dysfunction. A distinctive and pioneering expertise is glycation by the dicarbonyl metabolite methylglyoxal and prevention of this by the glyoxalase system. Diseases under current investigation are: vascular complications of diabetes, renal failure, ageing and glyoxalase 1-linked multidrug resistant tumours. Novel therapeutics development under current investigation are: glyoxalase 1 inducers, glyoxalase 1 inhibitors and Nrf2 activators. I have a particular interest in: (i) inducers of glyoxalase 1 for diabetic vascular disease and healthy ageing, and (ii) glyoxalase 1 inhibitors for glyoxalase 1-mediated multidrug resistant tumours. Novel diagnostics under investigation are: biomarkers for vascular and metabolic health, and healthy ageing.


RESEARCH GROUPS



BACKGROUND


I am a biomedical researcher and research team leader working in translational medicine, diet and health, development of functional foods and pharmaceuticals and systems biology. I lead research on the formation of the reactive dicarbonyl metabolite methylglyoxal and its metabolism by the glyoxalase system in human health and disease. Accumulation of methylglyoxal ‒ dicarbonyl stress ‒ is a new type of metabolic imbalance that is providing improved understanding of disease, health decline in ageing and new routes to treatment. The key enzyme of this system, glyoxalase 1 (Glo1), is now a target for Glo1 inducer development as active agents of functional foods for healthy ageing ‒ particularly to counter development of diabetes, obesity and cardiovascular disease, and pharmaceuticals for treatment of vascular complications of diabetes ‒ particularly diabetic renal disease, renal failure, neurological disorders and other disease. Glo1 inhibition is a strategy for development of novel antitumour agents. Increased Glo1 copy number occurs in refractory tumours is associated with multidrug resistance (MDR) and sensitivity to Glo1 inhibitors. Glo1 inhibitor therapy would likely active particularly against MDR breast cancer and lung cancer. I have experience in cellular, pre-clinical and clinical studies. I lead a multidisciplinary team of biomedical and clinical investigators. I have published 260 peer-reviewed articles and 190 conference papers with h-factor 63. I collaborate with leading experts in biomedical research worldwide and partners in the food and pharmaceutical industries.

CURRENT RESEARCH PROJECTS


  • Effect of glyoxalase 1 silencing in human cells in vitro, with Naila Rabbani, Funded by: Saudi Arabian Ministry of Education, Project Start Date: 01/10/2012 Project End Date: 30/09/2015

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SELECTED PUBLICATIONS


  • Xue, M., Momiji, H., Rabbani, R., Barker, G., Shmygol, A., Bretschneider, T., Rand, D.A. and Thornalley, P.J. (2015) 'Frequency modulated translocational oscillations of Nrf2 mediate the ARE cytoprotective transcriptional response.' Anti-Oxidants & Redox Signalling in press
  • Xue, M., Momiji, H., Rabbani, R., Bretschneider, T., Rand, D.A. and Thornalley, P.J. (2015) 'Frequency modulated translocational oscillations of Nrf2 - a transcription factor functioning like a wireless sensor.' Biochemical Society Transactions in press.
  • Waris, S., Winklhofer-Roob, B.M., Roob, J.M., Fuchs, S., Sourij, H., Rabbani, N. and Thornalley, P.J. (2015) 'Increased dicarbonyl glycation and oxidation adducts of deoxyguanosine in plasma and urine of patients with type 2 diabetes and link to diabetic nephropathy. J. Diabetes Res.' 915486, 1 - 10
  • Ahmed, U., Savage, R.S., Anwar, M.M., Costa, M.L., Filer, A., Raza, K., Watts, R.A., Winyard, P.G., Tarr, J., Haigh, R.C., Thornalley, P.J. and Rabbani, N. (2015) 'Biomarker combination detects early-stage and discriminates osteoarthritis, rheumatoid arthritis and other inflammatory joint disease.' Scientific Reports 5, 9259
  • Rabbani, N. and Thornalley, P.J. (2015) 'The hidden complexities in measurement of fructosyl-lysine and advanced glycation endproducts for risk prediction of vascular complications of diabetes.' Diabetes 64, 9 - 11

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Conferences


RESEARCH DEGREES SUPERVISED

  • Effect of dicarbonyl glycation on the development of diabetic complications, Date of Completion: 2014
  • Anti-stress gene response in cell and tissue ageing: role of transcription factor NF-E2-related factor-2 and effect of dietary activators, Date of Completion: 2014
  • Effect of dicarbonyl glycation of pancreatic beta-cell function, Date of Completion: 2013
  • Dicarbonyl glycation and endothelial dysfunction in hyperglycaemia associated with diabetes, Date of Completion: 2012
  • Mechanism of increased renal clearance of thiamine in hyperglycaemia associated with diabetes, Date of Completion: 2012
  • Biomarkers of protein damage in athritis, Date of Completion: 2011
  • The role of the kidney in diabetic thiamine deficiency, Date of Completion: 2010
  • Preparation and measurement of dicarbonyl glycation adducts of deoxyguanosine in diabetes and multidrug resistance associated with glyoxalase 1, Date of Completion: 2009
  • Glycation of human serum albumin, haemoglobin and lens crystallins and capsule collagen by methylglyoxal and other alpha-oxoaldehydes in vivo, Date of Completion: 2009
  • Methylglyoxal as a downstream mediator of antitumour drug cytotoxicity and link to glyoxalase 1 - associated multidrug resistance, Date of Completion: 2008
  • Pharmacokinetics and pharmacodynamics of high dose therapy with thiamine and Benfotiamine in diabetes, Date of Completion: 2007
  • Preparation and measurement of dicarbonyl glycation adducts of deoxyguanosine., Date of Completion: 2007
  • Studies of the prevention of diabetic nephropathy by thiamine. Protein damage studies., Date of Completion: 2007
  • Induction of antioxidant response element - linked gene expression by dietary isothiocyanates, Date of Completion: 2007
  • Glycation of collagen in health and disease - structural and functional studies, Date of Completion: 2007
  • Studies of the prevention of diabetic nephropathy by thiamine. Protein kinase C studies, Date of Completion: 2003
  • Studies on the formation, metabolism and glycation reactions of endogenous and exogenous alpha-oxoaldehydes in uraemia, Date of Completion: 2003
  • Study on the chromatographic analysis of glycation adducts, Date of Completion: 2002
  • Thiamine metabolism associated with biochemical dysfunction in diabetes mellitus and triosephosphate isomerase deficiency, Date of Completion: 2001

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My Profile last updated: 13/05/2015