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Research outline - Centre for Vascular Research University of Sydney

Within: Bosch Institute, Discipline of Pathology

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Overview of research program

The research program in our laboratory focuses on oxidative processes in vascular medicine

Current research projects aim to:

  • Develop novel redox-active drugs that protect against atherosclerotic diseases and diabetes based on their ability to induce the enzyme heme oxygenase-1.
  • Enhance present knowledge of heme oxygenase-1 biology at the cellular and whole organism level, with an emphasis on the ability of the enzyme to regulate cell growth, iron homeostasis, and antioxidant activity.
  • Investigate the contribution of the enzyme indoleamine 2,3-dioxygense to the regulation of vascular tone, with an emphasis on inflammation and interaction with nitric oxide synthase.
  • Identify oxidants and enzymes that affect the redox state and redox processes following receptor tyrosine kinase activation on endothelial cell lines.
  • Examine the effect of HO-1 on diabetes and insulin resistance with a view to determining therapeutic targets for type 2 diabetes.
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Major funding sources

  • Regulation of vascular tone by kynurenine: NHMRC Project Grants - $639,000
  • Cellular Responses to Adversity: Oxidative Stress and Protection Against Oxidative Damage. ARC Discovery Project - $304,000
  • Vascular Biology: NHMRC Program Grant. Shared Support - $2,356,475
  • Senior Principal Research Fellowship: NHMRC Research Fellowships - $905,000
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Selected publications

  • Coleman, P, Hahn, C, Grimshaw, M, Lu, Y, Li, X, Brautigan, P, Beck, K, Stocker, R, Vadas, M, Gamble, J. Stress-induced premature senescence mediated by a novel gene, SENEX, results in an anti-inflammatory phenotype in endothelial cells. Blood. 2010; 116:4016-24
  • Beck, K, Wu, B, Ni, J, Santiago, F, Malabanan, K, Li, C, Wang, Y, Khachigian, L, Stocker, R. Interplay Between Heme Oxygenase-1 and the Multifunctional Transcription Factor Yin Yang 1 in the Inhibition of Intimal Hyperplasia. Circulation Research. 2010; 0:0
  • Kathir, K, Dennis, J, Croft, K, Mori, T, Lau, A, Adams, M, Stocker, R. Equivalent lipid oxidation profiles in advanced atherosclerotic lesions of carotid endarterectomy plaques obtained from symptomatic type 2 diabetic and non-diabetic subjects. Free radical biology & medicine. 2010; 49:481-6
  • Wang Y, Liu H, McKenzie G, Witting PK, Stasch J-P, Hahn M, Changsirivathanathamrong D, Wu BJ, Ball HJ, Thomas SR, Kapoor V, Celermajer DS, Mellor AL, Keaney JF Jr, Hunt NH, Stocker R. Kynurenine is an endothelium-derived relaxing factor produced during inflammation. Nat Med 2010;16:279-285
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Major collaborations

  • United States. (University of Washington, Seattle) Collaboration with Professor Jay Heinecke: "The effect of heme oxygenase-1 expression on the macrophage proteome"..
  • Switzerland. (University of Geneva) Professor Karl-Heinz Krause.
  • Singapore. (National University of Singapore) 1. Joint research project grant from the Biomedical Research Council & National Medical Research Council with Professors Barry Halliwell and Frank Watt: "Mechanisms of vascular protection by haem oxygenase". 2. Collaboration with Professor Markus Wenk on the use of lipidomics to identify novel markers for cardiovascular disease.
  • United States. (University of Massachusetts Medical School) Professor John Keaney.
  • Switzerland. (University of Geneva) Professor Beat Imhof.
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