Research outline - Redox Biology Group

Within: Bosch Institute, Discipline of Pathology

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Overview of research program

Cardiovascular disease is increasingly the single greatest cause of mortality and morbidity in the Western world. The main research thrust of the Redox Biology Group involves design and testing of potential (synthetic antioxidant) inhibitors of damage to myocardial and neuronal tissues in the setting of acute heart or brain attack (stroke). This area research has gained momentum with the collaboration of a synthetic organic chemist from the United States (A/ Prof. Brian Salvatore) who has synthesized a series of analogues derived from a lead compound identified by Dr Witting and his research team. These analogues are now being tested for their cardio- and neuro-protective efficacy in relevant animal models of acute disease.

In another theme area of research, Dr Witting has rekindled close links with his former mentor Professor Peter Lay in the School of Chemistry. Here the researchers are collaborating on the use of synchrotron radiation to determine changes in the cellular composition of metal ions by comparing normal cells derived from the heart or brain with those challenged by experimental ischemia reperfusion injury to simulate heart attack or stroke, respectively. Other collaborations include working closely with Associate Professor John Wheatley (Respiratory Medicine and Sleep Disorders, Westmead Hospital) and Associate Professor Qihan Dong (Cancer Genetics Group, Bosch Institute, The University of Sydney).

The laboratory has gained funding from a variety of sources including philanthropic Foundations, mainstream government bodies such as the ARC, Diabetes Australia, the National Heart Foundation of Australia and Industry (Eli Lilly). Importantly, the lab continues to support young undergraduate and postgraduate researchers and the mixture of senior staff, research assistants and students makes for an ideal training base for young researchers. In 2007, Mr Shane Antao (Honours student) was awarded the Concord Hospital Basic Science award, and he also received Nationally competitive Travel and Best Poster awards from the Australian Atherosclerosis Society. In addition, Ms Elicia Rodas (2008 summer student) was awarded equal second place in The University of Sydney (Medical Faculty) Dean's Award for best summer project.

Major funding sources

  • The fate of dietary selenium in vivo; a direct approach to linking chemical form with biological activity: ARC Shared Research Support - $80,000
  • The Role of Snoring Vibrations in the Pathogenesis of Early Carotid Artery Atherosclerosis: NHMRC Project Grants - $570,075
  • Cellular response to pro-oxidative myoglobin: ARC Discovery Projects - $420,000

Selected publications

  • Morrison, D, Issa, F, Bhadbhade, M, Groebler, L, Witting, P, Kassiou, M, Rutledge, P, Rendina, L. Boronated phosphonium salts containing arylboronic acid, closo-carborane, or nido-carborane: synthesis, X-ray diffraction, in vitro cytotoxicity, and cellular uptake. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry. 2010; 15:1305-18
  • Antao, S, Duong, T, Aran, R, Witting, P. Neuroglobin over-expression in cultured human neuronal cells protects against hydrogen peroxide insult via activating phosphoinositide-3 kinase and opening the mitochondrial KATP channel. Antioxidants & redox signaling. 2010; 13:769-81
  • Shanu, A, Parry, S, Wood, S, Rodas, E, Witting, P. The synthetic polyphenol tert-butyl-bisphenol inhibits myoglobin-induced dysfunction in cultured kidney epithelial cells. Free radical research. 2010; 44:843-53

Major collaborations

  • New Zealand. (Otago University (Dunedin)) Seleno-organic compounds as antioxidants.
  • Canada. (The University of British Columbia) Collaborative work with Professor A. Grant Mauk.