Research Network for Metals in Medicine

 

 

Dr Michael Davies

BSc, DPhil(York)

Position: Deputy Director, The Heart Research Institute

Affiliation: The Heart Research Institute

Postal Address:
The Heart Research Institute
145 Missenden Road
Camperdown,Sydney
New South Wales, 2050
AUSTRALIA

Phone: +61 (2) 9550 3560
Fax: +61 (2) 9550 3302
Email: m.davies@hri.org.au
Webpage: http://www.hri.org.au/


Research Profile

Michael Davies was awarded his B.Sc. (1981) and D.Phil. (1984) degrees from University of York, UK. After post-doctoral studies at Brunel University in London, he was appointed as a lecturer at the University of York in 1987. He moved to Australia in late 1995 to take up a position as a Group Leader at the Heart Research Institute, Sydney, on a Australian Research Council QE2 Fellowship. He was promoted to a Senior / Professorial Fellowship in 2000, and the Deputy Directorship of the Institute in 2001. In 2003 he was awarded the Silver Medal of the International EPR Society for his work in Biology / Medicine. His primary research interests lie in mechanisms of protein oxidation, particularly those catalysed by metal ions, the biological consequences of such reactions, and the development of methods to quantify oxidative damage in vivo.

Dr. Davies is a well-established scientist and international leader in the field of protein oxidation and is spearheading new developments in the understanding of the specifics of peptide and protein oxidation, and its biological consequences. In particular, he pioneered the use of EPR spectroscopy with spin trapping to examine radicals formed on proteins (see publication list). In recent years he has combined this approach with a systematic identification of the products that arise as a result of the oxidation of protein side-chains and the backbone. He has, together with Prof. Dean, developed a number of assays which have allowed the quantification of specific side-chain oxidation products and this technology has been applied, very successfully, to examine the role of protein oxidation in various human diseases and ageing. He has identified a number of key rearrangement and fragmentation processes that occur during the oxidation of amino acids, peptides and proteins, including novel backbone fragmentation pathways and reactions which result in the transfer of damage from protein side-chains to the backbone. He has established that oxidative damage can be transferred both within, and between proteins, and has elucidated a number of these pathways. He has carried out extensive studies on protein peroxides and other oxidation products (e.g. DOPA) and has demonstrated that these are key intermediates in protein oxidation, and are capable of transferring damage to other targets. He written a number of major reviews on the subject of protein oxidation and, with Prof. Dean, written the only monograph on the subject of protein oxidation (Davies, MJ, & Dean, RT (1997) “Radical mediated protein oxidation: from chemistry to medicine”, Oxford University Press, pp. 1-443).

Dr. Davies has extensive experience in managing scientific projects and staff, and has guided > 15 PhD students to successful completion. He is a former recipient of a Career Development Award from the YCRC (UK) and an ARC QEII fellowship, and currently holds an ARC Senior / Professorial Fellowship. His work in EPR was recently recognised, at an international level, by the award of the 2003 Silver medal of the International EPR Society for work in Biology and Medicine. He is currently deputy director of the Heart Research Institute and holds honorary academic posts at Sydney and Macquarie Universities. He reviews grants applications for a large number of national and international grant bodies, and is regularly invited to speak at international conferences (e.g. 2002: invited lecture - Gordon conference on Oxygen Radicals; plenary lecture – Int. Soc. for Free Radical Research (France); opening plenary - 7th Int. EPR Spin Trapping meeting (USA) and for 2003: invited lectures at – Amer. Society for Photobiology meeting, 12th Int. Congress on Radiation Research, and the 10th Oxygen Society meeting). He has considerable experience in the commercial development of scientific advances and holds 3 worldwide patents, one of which is a successful commercial product.

Dr. Davies is an editorial board member of a number of major journals (Free Radical Biology and Medicine, Chemical Research in Toxicology, Free Radical Research, Redox Report, Spectroscopy) and an Editorial Advisor for Biochemical Journal. He is co-editor of the Electron Paramagnetic Resonance series (Royal Society of Chemistry, UK; from 1993-present). He is currently President of the Society for Free Radical Research (Australasia), a member of the International Council of the Society for Free Radical Research, and a Council member of MEPSA. He is actively involved in organising national and international meetings including the 1999 and 2002 Society for Free Radical Research (Australasia) meetings, the 2001 and 2003 joint meeting of the Societies for Free Radical Research of Australasia and Japan, the 6th and 7th International meetings on EPR Spin Trapping (France - 2000, USA - 2002), was a session convenor for the 2003 Oxygen Society meeting, and on the International Scientific Program Committee and a session convenor for the 12th International Congress on Radiation Research.


Selected Publications

Books

  1. Gilbert, BC, Atherton, NM, & Davies, MJ (Eds.), (1998) Electron Paramagnetic Resonance, vol. 16, Royal Society of Chemistry, Cambridge, pp. 1-288.
  2. Gilbert, BC, Davies, MJ & McLauchlan, KM (Eds.), (2000) Electron Paramagnetic Resonance, vol. 17, Royal Society of Chemistry, Cambridge, pp. 1-332.
  3. Gilbert, B. C.; Davies, M. J.; Murphy, D. M. (Eds.) (2002) Electron Paramagnetic Resonance, vol. 18, Royal Society of Chemistry, Cambridge, pp. 1-372.

  4. Book Chapters

  5. Fu, S, Davies, MJ, & Dean, RT (1998) Molecular aspects of free radical damage to proteins, in Free Radicals and Molecular Biology of Human Diseases (eds. Aruoma, OI & Halliwell, B), OICA International, pp 29-56.
  6. Timmins, GS, Davies, MJ (1998) “Biological Free Radicals”, In: Gilbert, BC, Atherton, NM & Davies, MJ (Eds.), Electron Paramagnetic Resonance”, vol. 16, Royal Society of Chemistry, Cambridge, pp. 1-49.
  7. Fu, S, Dean, RT, Davies, MJ, & Heinecke, JW (2000) Protein oxidation in atherogenesis. In: (Dean, R. T., Kelly, D., eds.) “Atherosclerosis”, Oxford: Oxford University Press, pp. 301-325.
  8. Davies, MJ & Timmins, GS (2000) Biological free radicals. In: Gilbert, BC, Davies, MJ, McLauchlan, KM (Eds.), Electron Paramagnetic Resonance, vol. 17, Royal Society of Chemistry, Cambridge, 1-42.
  9. Davies, MJ & Truscott, RJW (2001) Photo-oxidation of proteins and its consequences, in "Sun protection in Man", Comprehensive Series in Photosciences, Volume 3, (Giacomoni, P., Ed.), Elsevier, Amsterdam, Chapter 12, pp. 251-275.
  10. Rees, MD, Hawkins, CL & Davies, MJ (2002) Polysaccharide fragmentation induced by hydroxyl radicals and hypochlorite, In Hyaluronan 2000 (Kennedy, JF, Phillips, GO, Williams PA, Eds.), Woodhead Publishing Ltd., Cambridge, Vol. 1, pp. 151-160.
  11. Morin, B, Fu, S, Wang, H, Davies, MJ, & Dean, RT (2002) Analysis of aliphatic amino acid alcohols in oxidised proteins, In: Oxidative stress: biomarkers and antioxidants, (Armstrong, D., Ed.), Humana Press, New Jersey, pp. 101-110.
  12. Davies, M. J. (2002) Recent developments in spin trapping. In:Gilbert, B. C.; M. J. Davies D. M. Murphy (Eds), Electron Paramagnetic Resonance, Vol.18. Cambridge: Royal Society of Chemistry, pp. 47-73.
  13. Journal Articles

  14. Mathieu, C, Moreau, S, Frendo, P, Puppo, A & Davies, MJ (1998) Direct detection of radicals in intact soybean nodules: presence of nitric oxide-leghemoglobin complexes, Free Radic. Biol. Med., 24, 1242-1249.
  15. Silvester, JA, Timmins, GS & Davies, MJ (1998) Photodynamically-generated bovine serum albumin radicals: evidence for damage transfer and oxidation at cysteine and tryptophan residues, Free Radic. Biol. Med., 24, 754-766.
  16. Silvester, JA, Timmins, GS & Davies, MJ (1998) Protein hydroperoxides and carbonyl groups generated by porphyrin-induced photo-oxidation of bovine serum albumin, Arch. Biochem. Biophys., 350, 249-258.
  17. Morin, B, Davies, MJ & Dean RT (1998) The protein oxidation product 3,4-dihydroxyphenylalanine (DOPA) mediates oxidative DNA damage, Biochem. J., 330, 1059-1067.
  18. Hawkins, CL & Davies, MJ (1998) Degradation of hyaluronic acid, poly- and mono-saccharides, and model compounds by hypochlorite: evidence for radical intermediates and fragmentation, Free Radic. Biol. Med., 24, 1396-1410.
  19. Fu, S, Davies, MJ, Stocker, R & Dean, RT (1998) Evidence for roles of radicals in protein oxidation in advanced atherosclerotic plaque, Biochem. J., 333, 519-525.
  20. Thomas, SR, Davies, MJ & Stocker, R (1998) Oxidation and antioxidation of human low density lipoprotein and plasma exposed to 3-morpholinosydnonimine and reagent peroxynitrite, Chem. Res. Toxicol., 11, 484-494.
  21. Park, JI, Grant, CM, Davies, MJ & Dawes, I (1998) The cytoplasmic Cu,Zn superoxide dismutase of saccharomyces cerevisiae is required for resistance to freeze-thaw stress: generation of free radicals during freezing and thawing, J. Biol. Chem., 273, 22921-22928.
  22. Hawkins, CL & Davies, MJ (1998) Hypochlorite-induced damage to proteins: formation of nitrogen-centred radicals from lysine residues and their role in protein fragmentation, Biochem. J., 332, 617-625.
  23. Hawkins, CL, Davies, MJ (1998) Reaction of HOCl with amino acids and peptides: EPR evidence for rapid rearrangement and fragmentation reactions of nitrogen-centered radicals, J. Chem. Soc., Perkin Trans. 2, 1937-1945.
  24. Morin, B, Bubb, WA, Davies, MJ, Dean, RT, Fu, S (1998) 3-Hydroxylysine, a potential marker for studying radical-induced protein oxidation, Chem. Res. Toxicol., 11, 1265-1273.
  25. Hawkins, CL, Davies, MJ (1998) EPR studies on the selectivity of hydroxyl radical attack on amino acids and peptides, J. Chem. Soc., Perkin Trans. 2, 2617-2622.
  26. Hawkins, CL & Davies, MJ (1998) Hypochlorite-induced oxidation of plasma proteins: formation of nitrogen-centred radicals and their role in protein fragmentation. Curr. Topics Biophys. 22 (Suppl. B), 89-98.
  27. Irwin, JA, Ostdal, H, & Davies, MJ (1999) Myoglobin-induced oxidative damage: evidence for radical transfer from oxidised myoglobin to other proteins and antioxidants, Arch. Biochem. Biophys., 362, 94-104.
  28. Ostdal, H, Andersen, HJ, & Davies, MJ (1999) Formation of long-lived radicals on proteins by radical transfer from heme enzymes - a common process?, Arch. Biochem. Biophys., 362, 105-112.
  29. Witting, PK, Willhite, CA, Davies, MJ & Stocker, R (1999) Lipid oxidation in human low-density lipoprotein induced by metmyoglobin /H2O2: Involvement of a-tocopheroxyl and phosphatidylcholine alkoxyl radicals, Chem. Res. Toxicol., 12, 1173-1181.
  30. Davies, MJ, Mathieu, C & Puppo, A (1999) Leghemoglobin: properties and reactions, Adv. Inorg. Chem., 46, 495-542.
  31. Al-Assaf, S, Hawkins, CL, Parsons, BJ, Davies, MJ, & Phillips, GO (1999) Identification of radicals from hyaluronan (hyaluronic acid) and cross-linked derivatives using electron paramagnetic resonance spectroscopy, Carbohyd. Polymers, 38, 17-22.
  32. Hazell, LJ, Davies, MJ, & Stocker, R (1999) Secondary radicals derived from chloramines of apolipoprotein B-100 contribute to HOCl-induced LDL lipid peroxidation, Biochem. J., 339, 489-495.
  33. Hawkins, CL, & Davies, MJ (1999) Hypochlorite-induced oxidation of proteins in plasma: formation of nitrogen-centred radicals and their role in protein fragmentation, Biochem. J., 340, 539-548.
  34. Davies, MJ, Fu, S, Wang, H, & Dean, RT (1999) Stable markers of oxidant damage to proteins and their application in the study of human disease. Free Radic. Biol. Med., 27, 1151-1163.
  35. Luxford, C, Morin, B, Dean, RT, & Davies, MJ (1999) Histone H1- and other protein and amino acid-hydroperoxides can give rise to free radicals which oxidise DNA. Biochem. J., 344, 125-134.
  36. Fu, S, Wang, H, Davies, MJ, & Dean, RT (2000) Reaction of hypochlorous acid with tyrosine and peptidyl-tyrosyl residues gives dichlorinated and aldehydic products in addition to 3-chlorotyrosine, J. Biol. Chem., 275, 10851-10858.
  37. Garner, B, Davies, MJ, & Truscott, RJW (2000) Formation of hydroxyl radicals in the human lens is related to the severity of nuclear cataract. Exp. Eye Res., 70, 81-88.
  38. Hawkins, CL & Davies, MJ (2000) Hypochlorite-induced damage to red blood cells: evidence for the formation of nitrogen-centred radicals. Redox Report, 5, 57-59.
  39. Wright, A, Hawkins, CL, & Davies, MJ (2000) Singlet oxygen-mediated protein oxidation: evidence for the formation of reactive peroxides. Redox Report, 5, 159-161.
  40. Pattison, DI, Lay, PA, & Davies, MJ (2000) An investigation into the genotoxic species generated during reduction of chromium(VI) by catechol(amine)s. Redox Report, 5, 130-132.
  41. Pattison, DI, Lay, PA & Davies, MJ (2000) EPR studies of Cr(V) intermediates generated via reduction of dichromate by DOPA and related catechol(amine)s: potential role for oxidised amino acids in Cr-induced cancers. Inorganic Chem., 39, 2729-2739.
  42. Luxford, C, Dean, RT, & Davies, MJ (2000) Radicals derived from histone hydroperoxides damage nucleobases in RNA and DNA. Chem. Res. Toxicol., 13, 665-672.
  43. Davies, MJ, & Hawkins, CL (2000) Hypochlorite-induced oxidation of thiols: formation of thiyl radicals and the role of sulfenyl chlorides as intermediates. Free Radic. Res. 33, 719-729.
  44. Headlam, HA, Mortimer, A, Easton, CJ & Davies, MJ (2000) Beta scission of C-3 (b-Carbon) alkoxyl radicals on peptides and proteins: a novel pathway which results in the formation of a-carbon radicals and loss of amino acid side-chains. Chem. Res. Toxicol., 13, 1087-1095.
  45. Hawkins, CL, & Davies, MJ (2001) Invited review: Generation and propagation of radical reactions on proteins. Biochim. Biophys. Acta, 1504, 196-219.
  46. Pattison, DI, Levina, A, Davies, MJ & Lay, PA (2001) An investigation of the chromium oxidation state of a monoanionic chromium tris(catecholate) complex by X-ray absorption and EPR spectroscopies. Inorganic Chem., 40, 214-217.
  47. Pattison, DI, Davies, MJ, Levina, A, Nixon, N.E. & Lay, PA (2001) Chromium(VI) reduction by catechol(amine)s results in DNA cleavage in vitro: relevance to chromium genotoxicity. Chem. Res. Toxicol., 14, 500-510.
  48. Linton, S, Davies, MJ, & Dean, RT (2001) Protein oxidation in ageing. Exp. Gerentol. 36, 1503-1518.
  49. Hawkins, CL and Davies, MJ (2001) Hypochlorite-induced damage to nucleosides: formation of chloramines and nitrogen-centered radicals, Chem. Res. Toxicol., 14, 1071-1081.
  50. Davies, MJ & Truscott, RJW (2001) Photo-oxidation of proteins and its role in cataractogenesis. J. Photochem. Photobiol. B, 63, 114-125.
  51. Pattison, D & Davies, MJ (2001) Absolute rate constants for the reaction of hypochlorous acid with protein side-chains and peptide bonds, Chem. Res. Toxicol., 14, 1453-1464.
  52. Hawkins, CL, Brown, BE, & Davies, MJ (2001) Hypochlorite- and hypobromite mediated radical formation and its role in cell lysis, Arch. Biochem. Biophys., 395, 137-145.
  53. Luxford, C, Dean, RT, & Davies, MJ (2002) Induction of DNA damage by oxidised amino acids and proteins. Biogerentology, 3, 95-102.
  54. Pattison, DI, Dean, RT & Davies, MJ (2002) Invited review: Oxidation of DNA, proteins and lipids by DOPA, protein-bound DOPA, and related catechols and catecholamines, Toxicology,177, 23-37.
  55. Hawkins, CL & Davies, MJ (2002) Hypochlorite-induced damage to DNA, RNA and polynucleosides: formation of chloramines and nitrogen-centered radicals, Chem. Res. Toxicol., 15, 83-92.
  56. Hawkins, CL, Rees, MD & Davies, MJ (2002) Superoxide radicals can act synergistically with hypochlorite to induce damage to proteins, FEBS Letts., 510, 41-44.
  57. Knott, HM, Baoutina, A, Davies, MJ & Dean, RT (2002) Comparative kinetics of copper-ion-mediated protein and lipid oxidation in low-density lipoprotein, Arch. Biochem. Biophys., 400, 223-232.
  58. Ostdal, H, Davies, MJ & Andersen, H.J. (2002) Reaction between protein radicals and other biomolecules, Free Radic. Biol. Med., 33, 201-209
  59. Morgan, PE, Dean, RT, & Davies, MJ (2002) Inhibition of glyceraldehyde-3-phosphate dehydrogenase by peptide and protein peroxides generated by singlet oxygen attack, Eur J. Biochem., 269, 1916-1925.
  60. Morgan, P. E.; Dean, R. T.; Davies, M. J. (2002) Inactivation of cellular enzymes by carbonyls and protein-bound glycation/glycoxidation products. Arch. Biochem. Biophys. 403:259-269.
  61. Pattison, D. I.; Davies, M. J.; Asmus, K.-D. (2002) Absolute rate constants for the formation of nitrogen-centred radicals from chloramines/amides and their reactions with antioxidants. J. Chem. Soc., Perkin Trans. 2 1461-1467.
  62. Hampton, M. B.; Morgan, P. E.; Davies, M. J. (2002) Inactivation of cellular caspases by peptide-derived tryptophan and tyrosine peroxides. FEBS Lett. 527:289-292.
  63. Headlam, H. A.; Davies, M. J. (2002) Beta-scission of side-chain alkoxyl radicals on peptides and proteins results in the loss of side chains as aldehydes and ketones. Free Radic. Biol. Med. 32:1171-1184.
  64. Hawkins, C. L.; Pattison, D. I.; Davies, M. J. (2002) Reaction of protein chloramines with DNA and nucleosides: evidence for the formation of radicals, protein-DNA cross-links and DNA fragmentation. Biochem. J. 365:605-615.
  65. Hawkins, C. L.; Davies, M. J. (2002) Comparison of 5,5-dimethyl-1-pyrroline-N-oxide and a new cyclic nitrone spin trap - 5-tert-butoxycarbonyl-5-methyl-1-pyrroline-N-oxide (BMPO) for the trapping of nitrogen-centred radicals. Curr. Topics Biophys. 26:137-144.
  66. Wright, A.; Bubb, W. A.; Hawkins, C. L.; Davies, M. J. (2002) Singlet oxygen-mediated protein oxidation: evidence for the formation of reactive side-chain peroxides on tyrosine residues. Photochem. Photobiol. 76; 35-46.
  67. Headlam, H. A.; Davies, M. J. (2003) Cell-mediated reduction of protein and peptide hydroperoxides to reactive free radicals. Free Radic. Biol. Med. 34:44-55.
  68. Wright, A.; Hawkins, C. L.; Davies, M. J. (2003) Photo-oxidation of cells generates long-lived intracellular protein peroxides. Free. Radic. Biol. Med. 34, 637-647.
  69. Woods, A. A.; Linton, S. L.; Davies, M. J. (2003) Detection of HOCl-mediated protein oxidation products in the extracellular matrix of human atherosclerotic plaques. Biochem. J. 370: 729-735.
  70. Pattison, D.I.; Hawkins, C.L.; Davies, M.J. (2003) Hypochlorous acid mediated oxidation of lipid components present in low-density lipoproteins: absolute rate constants, product analysis and computational modelling. Chem. Res. Toxicol. 16, 439-449.
  71. Hawkins, C.L.; Pattison, D.I.; Davies, M.J. (2003) Hypochlorite-induced oxidation of amino acids, peptides and proteins. Amino acids, 23, 259-274.
  72. Hagerman, A.E.; Dean, R.T.; Davies, M.J. (2003) Radical chemistry of epigallocatechin gallate and its relevance to protein damage. Arch. Biochem. Biophys., 414, 115-120.
  73. Belli, S.I.; Wallach, M.G.; Luxford, C.; Davies, M.J.; Smith, N.C. (2003) The role of tyrosine-rich precursor glycoproteins and dityrosine- /DOPA-mediated protein crosslinking in the development of the oocyst wall in the coccidian parasite Eimeria maxima. Eukaryotic Cell, 2, 456-464.
  74. Knott, H.M.; Brown, B.E.; Davies, M.J.; Dean, R.T. (2003) Glycation and glycoxidation of low-density lipoproteins by glucose and low-molecular-weight aldehydes: formation of modified and oxidized particles. Eur. J. Biochem. 270, 3572-3582.
  75. Davies, M.J. (2003) Mini-review. Singlet oxygen-mediated damage to proteins and its consequences. Biochem. Biophys. Res. Commun. 305, 761-770
  76. Woods, A.A.; Davies, M.J. (2003) Fragmentation of extracellular matrix by hypochlorous acid, Biochem. J., 376, 219-227.
  77. Rees, M.D.; Hawkins, C.L.; Davies, M.J. (2003) Hypochlorite-mediated fragmentation of hyaluronan, chondritin sulfates, and related N-acetyl glycosamines, J. Am. Chem. Soc., 125, 13719-13733.
  78. Van Reyk, D.M.; Gillies, M.C.; Davies, M.J. (2003) The retina: oxidative stress and diabetes, Redox Report, 8, 187-192.
  79. Davies, M.J.; Hawkins, C.L. (2003) Review: EPR spin trapping of protein radicals, Free Radic. Biol. Med., in press.
  80. Davies, M.J. (2003) Reactive species formed on proteins exposed to singlet oxygen, Photochem. Photobiol. Science, in press (accepted 7/8/2003).

Facilities

  • EPR Spectroscopy (Bruker EMX with various attachments).
  • Multiple HPLC systems with UV, fluorescence, multi-channel electrochemical, chemiluminescence and radiometric detectors for analysis of both normal (parent) and oxidised / modified proteins, lipids, and antioxidants.
  • GC/MS.


International Linkages

Prof. C. Schoneich (Univ of Kansas, USA)
Prof. I. Kochevar (Massachusetts General Hospital, USA)
Dr. M. Hampton (Christchurch School of Medicine, NZ)
Prof. C. Winterbourn (Christchurch School of Medicine, NZ)
Prof. S. Kawanishi (Mie University, Japan)