A strength of Mātai Hāora - Centre for Redox Biology and Medicine is our research on the biological chemistry of free radicals and antioxidant systems. This fundamental research provides a solid platform for our other research projects.
- Biochemistry of mammalian haem and thiol peroxidases
- Contribution of peroxiredoxins to redox signalling
- Impact of hypochlorous acid and hypothiocyanous acid on protein and cell function
- Developing and assessing the efficacy of myeloperoxidase inhibitors
- Role of low molecular weight thiols in bacterial antioxidant defence
- Redox regulation of cell death and epigenetic signalling pathways
- Regulation of the 2-oxoglutarate-dependent dioxygenases by ascorbate
- Redox regulation of cytoskeletal proteins and impact on the blood-brain barrier
Infectious disease
White blood cells called neutrophils ingest bacteria into phagosomes where they bombard them with oxidants. Some pathogenic bacteria are able to survive this attack and continue to replicate. Antibiotic resistance is a major concern and new antimicrobial strategies are urgently required. Compounds that improve the ability of neutrophils to kill bacteria may be valuable.
Our key research questions:
- How do neutrophils use oxidants to kill bacteria?
- How do pathogenic bacteria protect themselves from oxidative stress?
- Can we identify targets for sensitising pathogens to killing by oxidants?
- Are there oxidative biomarkers that enable diagnosis of bacterial infection?
Specific pathogens of interest:
- Staphylococcus aureus
- Streptococcus pneumoniae
- Mycobacterium tuberculosis
- Pseudomonas aeruginosa
Inflammation
Excessive production of oxidants by white blood cells can impact on neighbouring host cells and cause disruption. The focus has traditionally been on how oxidants damage and kill cells, but oxidants may have more subtle effects on redox-sensitive signalling pathways in cells. Compounds that modulate these pathways may be more effective than attempts to scavenge the oxidants themselves.
Our key research questions:
- How do immune cell oxidants impact on the function of neighbouring cells?
- How can host cells be protected from exposure to oxidative stress?
- Are there oxidative biomarkers that provide information on disease progression?
Specific diseases of interest:
- Inflammatory bowel disease
- Cystic fibrosis
- Alzheimer's disease
- Heart disease
Cancer
Genetic reprogramming and the tumour microenvironment are proposed to place cancer cells under increased levels of oxidative stress. Cancers may adapt by bolstering their antioxidant defences, but they may also be vulnerable to additional oxidative stress.
Our key research questions:
- Are cancer cells under more oxidative stress than normal cells?
- How does oxidative stress affect metabolic pathways and tumour metastasis?
- Can the antioxidant systems of cancer cells be targeted to enhance tumour killing?
Specific cancers of interest:
- Melanoma
- Leukaemia
- Breast cancer
- Colorectal cancer
Ageing
Ageing is associated with an increased incidence of a number of human diseases, and is linked to increased oxidant production and a decline in antioxidant capacity. However, the details of these processes are unclear. Increased understanding may lead to strategies that optimise healthy ageing.
Our key research questions:
- Can we measure oxidative stress and mitochondrial dysfunction in ageing populations?
- What impact does ageing have on cellular antioxidant systems?
Specific cohorts:
- Dunedin Multidisciplinary Health and Development Study
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