Research Network for Metals in Medicine

 

 

Professor Roland Stocker

Position: NHMRC Senior Research Fellow

Affiliation: Department of Pathology, School of Medical Sciences, University of New South Wales

Postal Address:
School of Medical Sciences
The University of New South Wales
UNSW Sydney NSW 2052
AUSTRALIA

Phone: +61 (02) 9385 1309
Email: r.stocker@unsw.edu.au
Webpage: http://notes.med.unsw.edu.au/medsciences.nsf/staff/3068419?OpenDocument


Research Profile

Publications (since 1982): 133 Peer-reviewed articles, with average impact factor of ~5.0 and ~80% as first or senior (last) author; 26 Invited articles and reviews; 14 Book chapters; 5 Patent (applications). These include 2 Citations Classic (>500 citations), and one in eight of these papers have been cited more than 100-times.

Awards & Grants (since 1987): 10 personal awards; 30 competitive government grants; 12 commercial grants.

Personal Invitations to Present at National and International Meetings (since 1988): 81 Invitations, including Gordon Conferences (3), FASEB Meetings (2), Harden Conference (1), and Plenary Lectures at International Conferences (6).

Contributions to field: Consultant to: Nutrition and Metabolism Advisory Committee, National Heart Foundation, Australia; Panel on Dietary Antioxidants and Related Compounds, National Academy of Sciences (USA); FDA (USA) on the use of coenzyme Q10 supplements; Executive Director of Heart Research Developments Pty Ltd (94-02); Chairman, Scientific Advisory Committee, International Association of Coenzyme Q10; Deputy Director, Heart Research Institute (00-01); Associate Editor: Journal of Lipid Research; Past and Present Member of Editorial Boards: Redox Report; Archives in Biochemistry and Biophysics; Free Radicals in Biology & Medicine; Free Radical Research; Chemistry Research Toxicology; President Society for Free Radical Research, Australasia (97-99); Public Officer Sydney Free Radical Inc., Committee Member International Society for Free Radical Research (96-01); Commercialisation interactions with Heart Research Developments Pty Ltd, AstraHässle now Astra/Zeneca (Sweden) and Chugai Pharmaceutica (Japan)

Professor Roland Stocker has made major contributions in understanding the chemistry and biology of oxidative damage to cells and the role of antioxidants. His group not only carries innovative, high quality academic research, but also seeks to develop this basic research through to the applied field (he is the inventor of three patents). He has made many significant contributions in the field of oxidative stress in atherosclerosis. In his earlier work he identified bilirubin as a functional antioxidant. This was reported in a Science paper that has become a citation classic (>900 citations), and the work has since been extended to cell protective properties of haem oxygenase. This enzyme, which degrades haem to biliverdin, carbon monoxide and iron, plays a central role in cellular iron metabolism, although it remains to be established how precisely this achieved. The Metals Network is ideally placed to make a unique and important contribution to this question. In addition, the group has made significant contribution to the understanding of the function and physiological role of indoleamine 2,3-dioxygenase, a haem-containing enzyme strongly induced under inflammatory conditions.

Subsequently, in a series of important papers Stocker’s group established the roles of various antioxidant defence systems in tissues, including the vitamin C, ubiquinol and vitamin E-based systems. In a serried of papers, his group provided a novel insight into the basic mechanism by which vitamin E (alpha-tocopherol) acts in lipoproteins. His group was also the first evidence that lipoproteins, including LDL are modified by hypochlorous acid, and they have contributed significantly to the literature on protein modification by oxidants, its underlying chemistry as well as that of antioxidants, particularly in atherosclerosis.



Selected Publications

  1. Sanni LA, Fu S, Dean RT, Bloomfield G, Stocker R, Chaudhri G, Dinauer MC, Hunt NH. Are reactive oxygen species involved in the pathogenesis of murine cerebral malaria? J Infect Dis 1999;179:217-222
  2. Witting PK, Pettersson K, Lindqvist A-M, Westerlund C, Westin Eriksson A, Stocker R. Inhibition by a co-antioxidant of aortic lipid peroxidation and atherosclerosis in apolipoprotein E and low density lipoprotein receptor gene double knockout mice. FASEB J 1999;13:667-675
  3. Upston JM, Terentis AC, Stocker R. Tocopherol-mediated peroxidation (TMP) of lipoproteins: implications for vitamin E as a potential antiatherogenic supplement. FASEB J1999;13:977-994
  4. Simons LA, von Konigsmark M, Simons J, Stocker R, Celermajer DS. Vitamin E does not improve arterial endothelial dysfunction in older adults. Atherosclerosis 1999;143:193-199
  5. Niu X, Zammit V, Dean RT, May J, Stocker R. Co-existence of oxidized lipids and ?-tocopherol in all lipoprotein fractions isolated from advanced human atherosclerotic plaques. Arterioscl Thromb Vasc Biol 1999;19:1708-1718
  6. Mohr D, Umeda Y, Redgrave TG, Stocker R. Antioxidant defenses in rat intestine and mesenteric lymph. Redox Report 1999;4:79-87
  7. Hazell LJ, Davies MJ, Stocker R. Secondary radicals derived from chloramines of apolipoprotein B 100 contribute to HOCl-induced LDL lipid peroxidation. Biochem J 1999;339:489-495
  8. Letters J, Christison JK, Witting PK, Westin Eriksson A, Pettersson K, Stocker R. Changes to lipids and antioxidants in plasma and aortae of apoE-deficient mice. J Lipid Res 1999;40:1104-1112
  9. Witting PK, Willhite CA, Davies MJ, Stocker R. Lipid oxidation in human low density lipoprotein induced by metmyoglobin/H2O2: involvement of ?-tocopheroxyl and phosphatidylcholine alkoxyl radicals. Chem Res Toxicol 1999;12:1173-1181
  10. Adams R, Phu CV, Stocker R, Celermajer DS. Lack of antioxidant activity of the antiatherogenic compound L-arginine. Atherosclerosis 1999;146:329-336
  11. Stocker R. The ambivalence of vitamin E in atherogenesis. Trends in Biological Sciences 1999;24:219-223
  12. Witting PK, Pettersson K, Östlund-Lindqvist A-M, Westerlund C, Westin Eriksson A, Wågberg M, Stocker R. Dissociation of atherogenesis from aortic accumulation of lipid hydro(pero)xides in Watanabe heritable hyperlipidemic rabbits. J Clin Invest 1999;104:213-220
  13. Upston JM, Karjalainen A, Bygrave FL, Stocker R. Efflux of hepatic ascorbate. A potential contributor to the maintenance of plasma vitamin C. Biochem J 1999;342:49-56
  14. Tomasetti M, Littarru GP, Stocker R, Alleva R. Coenzyme Q10 enrichment decreases oxidative DNA damage in human lymphocytes. Free Radic Biol Med 1999,27:1027-1032
  15. Thomas SR, Stocker R. Redox reactions related to indoleamine 2,3-dioxygenase and tryptophan metabolism along the kynurenine pathway. Redox Report 1999;4:199-220
  16. Raitakari, OT, McCredie RJ, Letters J, Witting PK, Griffiths KA, Sullivan D, Stocker R, Celermajer DS. Coenzyme Q improves LDL resistance to ex vivo oxidation but does not enhance endothelial function in hypercholesterolemic young adults. Free Radic Biol Med 2000;28:1100-1105
  17. Witting PK, Pettersson K, Letters J, Stocker R. Site-specific anti-atherogenic effect of probucol in apolipoprotein E deficient mice. Arterioscl Thromb Vasc Biol 2000;20:e26-e33
  18. Panzenböck U, Kritharides L, Raftery M, Rye K-A, Stocker R. Oxidation of methionine residues to methionine sulfoxides enhances rather than decreases potential anti-atherogenic properties of apolipoprotein A-I. J Biol Chem 2000;275:19536-19544
  19. Thomas SR, Stocker R. Molecular action of vitamin E during lipoprotein oxidation. Implications for atherosclerosis. Free Radic Biol Med 2000;28:1795-1805
  20. Witting PK, Pettersson K, Letters J, Stocker R. Anti-atherogenic effect of coenzyme Q10 in apolipoprotein E gene knockout mice. Free Radic Biol Med 2000;29:295-305
  21. Raitakari, OT, Adams MR, McCredie RJ, Griffiths KA, Stocker R, Celermajer DS. Oral vitamin C and endothelial function in smokers: short-term improvement, but no sustained beneficial effect. J Am Coll Cardiol 2000;35:1616-1621
  22. Lau AK, Witting PK, Chaufour C, Celermajer DS, Pettersson K, Stocker R. Protective effects of probucol in two animal models of atherosclerosis. Redox Rep 2000;5:116-118
  23. Carr AC, Myzak MC, Stocker R, McCall MR, Frei B. Myeloperoxidase binds to low-density lipoprotein: potential implications for atherosclerosis. FEBS Lett 2000;487:176-180
  24. Silvers KM, Sluis KB, Darlow BA, McGill F, Stocker R, Winterbourn CC. Limiting light-induced lipid peroxidation and vitamin loss in infant parenteral nutrition by adding multivitamin preparations to Intralipid. Acta Paediatr 2001;90:242-249
  25. Thomas SR, Leichtweis SB, Pettersson K, Croft K, Mori T, Brown AJ, Stocker R. Dietary co-supplementation with coenzyme Q10 and vitamin E inhibits atherosclerosis in apolipoprotein E gene knockout mice. Arterioscl Thromb Vasc Biol 2001;21:585-593
  26. Heydeck D, Upston JM, Viita H, Ylä-Herttuala S, Stocker R. Oxidation of low-density lipoprotein by rabbit and human 15-lipoxygenase: Prevalence of non-enzymatic reactions. J Lipid Res 2001;42:1082-1088
  27. Carr AC, Hawkins CL, Thomas SR, Stocker R, Frei B. Relative reactivities of N-chloramines and hypochlorous acid with human plasma constituents. Free Radic Biol Med 2001;30:526-536
  28. Thomas SR, Salahifar H, Mashima R, Hunt NH, Richardson D, Stocker R. Antioxidants inhibit indoleamine 2,3-dioxygenase in interferon-activated human macrophages. Post-translational regulation by pyrrolidine dithiocarbamate. J Immunol 2001;166:6332-6340
  29. Sanni LA, Rae C, Maitland A, Stocker R, Hunt NH. Is ischemia involved in the pathogenesis of murine cerebral malaria? Am J Pathol 2001;159:1105-1112
  30. Witting PK, Mauk GA, Douglas DJ, Stocker R. Reaction of human myoglobin and peroxynitrite: characterizing biomarkers for myoglobin-derived oxidative stress. Biochem Biophys Res Commun 2001;286:352-356.
  31. Oram JF, Vaughan A, Stocker R. ATP-binding cassette transporter A1 mediates cellular secretion of ? tocopherol. J Biol Chem 2001;276:39898-39902
  32. Upston JM, Witting PK, Brown AJ, Stocker R, Keaney JF, Jr. Effect of vitamin E on aortic lipid oxidation and intimal proliferation after arterial injury in cholesterol-fed rabbits. Free Radic Biol Med 2001;31:1245-1253
  33. Hazell LJ, Baernthaler G, Stocker R. Correlation between intimal thickness, apolipoprotein B-100 and hypochlorite-oxidized proteins in human atherosclerosis. Free Radic Biol Med 2001;31:1254-1262
  34. Upston JM, Niu X, Brown AJ, Mashima R, Wang H, Senthilmohan R, Kettle AJ, Dean RT, and Stocker R. Disease stage-dependent accumulation of lipid and protein oxidation products in human atherosclerosis. Am J Pathol 2002;160:701-710
  35. Terentis AC, Thomas SR, Burr JA, Liebler DC, Stocker R. Vitamin E oxidation in human atherosclerotic lesions. Circ Res 2002;90:333-339
  36. Bräsen JH, Koenig K, Bach H, Heinle H, Witting PK, Ylä-Herttuala S, Stocker R, Beisiegel U. Comparison of the effects of ?-tocopherol, ubiquinone-10 and probucol at therapeutic doses on atherosclerosis in WHHL rabbits. Atherosclerosis 2002;163:249-259
  37. Kritharides L, Stocker R. The use of antioxidant supplements in coronary heart disease. NHF Position statement. Atherosclerosis 2002;164:211-219
  38. Garner B, Priestman DA, Stocker R, Harvey DJ, Butters TD, Platt FM. Increased glycosphingolipid levels in serum and aortae of apolipoprotein E gene knockout mice. J Lipid Res 2002;43:204-215
  39. Medana IM, Hien TT, Day NP, Phu NH, Mai NTH, Chu’ong LV, Chau TTH, Taylor A, Salahifar H, Stocker R, Smythe G, Turner GDH, Farrar J, White NJ, Hunt NH. The clinical significance of cerebrospinal fluid levels of kynurenine pathway metabolites and lactate in severe malaria. J Infect Dis 2002;185:650-656
  40. Upston JM, Terentis AC, Morris K, Keaney JF, Jr, Stocker R. Oxidized lipid accumulates in the presence of ? tocopherol in atherosclerosis. Biochem J 2002;363:753-760
  41. Hazell LJ, Fu H, Dean RT, Stocker R, Truscott RJ. Is hypochlorous acid (HOCl) involved in age-related nuclear cataract? Clin Exp Optom 2002;85:97-100
  42. Mashima R, Tilley L, Siomos M-A, Papalexis V, Raftery MJ, Stocker R. Plasmodium falciparum histidine-rich protein-2 (PfHRP2) modulates the redox-activity of ferri-protoporphyrin IX (FePPIX): peroxidase-like activity of the PfHRP2-FePPIX complex. J Biol Chem 2002;277:14514-14520
  43. Terentis AC, Thomas SR, Takikawa O, Littlejohn TK, Truscott RJW, Armstrong RL, Yeh S-R, Stocker R. The heme environment of recombinant human indoleamine 2,3 dioxygenase. Structural properties and substrate-ligand interactions. J Biol Chem 2002;277:15788-15784
  44. Zhang W-J, Stocker R, McCall M, Forte TM, Frei B. Lack of inhibitory effect of HDL on TNF?-induced adhesion molecule expression in human aortic endothelial cells. Atherosclerosis 2002;165:241-249
  45. Rye KA, Duong MN, Psaltis M, Curtiss LK, Bonnet DJ, Stocker R, Barter PJ. Evidence that phospholipids play a key role in pre-? apoA-I formation and high density lipoprotein remodeling. Biochemistry 2002;41:12538-12545
  46. Pankhurst G, Wang XL, Wilcken DE, Baernthaler G, Panzenböck U, Stocker R. Characterization of specifically oxidized apolipoproteins in mildly oxidized high-density lipoproteins. J Lipid Res 2003;44:349-355
  47. Lau A, Leichtweis SB, Hume P, Mashima R, Hou JY, Chaufour X, Wilkinson B, Hunt NH, Celermajer DS Stocker R. Probucol promotes functional re-endothelialzation in balloon-injured rabbit aortas. Circulation 2003;107:2031-2036
  48. Choy KJ, Deng YM, Hou H, Wu B, Lau A, Witting PK, Stocker R. Coenzyme Q10 supplementation inhibits aortic lipid oxidation but fails to attenuate intimal thickening in balloon-injured New Zealand White rabbits Free Radic Biol Med 2003;35:300-309
  49. Martinic G, Hazell L, Stocker R. Vascular microdissection, perfusion, and excision of the murine arterial tree for use in atherogenic disease investigations. Contemporary Topics Lab Animal Sci 2003;42:48-53
  50. Stocker R, O’Halloran RA. De-alcoholized red wine decreases atherosclerosis in apolipoprotein E gene-deficient mice independent of inhibition of lipid peroxidation in the artery wall. Am J Clin Nutr 2004;79:123-130
  51. Wang XL, Rainwater D, Mahaney M, Stocker R. Co-Supplementation of vitamin E and coenzyme Q10 decreases circulating markers of inflammation in baboons. Am J Clin Nutr 2004,in press.


Facilities

The particular facilities of the group of Stocker include purified haem proteins, cultured cells reflecting altered iron metabolism, and other biological materials to probe for physiological relevance of chemical/biochemical studies.


International Linkages

Professor Stocker has an appointment as Adjunct Professor at Boston University, Faculty of Medicine, Whittaker Cardiovascular Research Institute. This provides access to transgenic animal facilities, including the generation of cell-specific expression of indoleamine 2,3-dioxygenase that will provide useful biological materials for the Metals Network.