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A postgraduate research opportunity at the University of Otago.

Details

Close date
Sunday, 27 February 2022
Academic background
Sciences, Health Sciences
Host campus
Christchurch
Qualification
Honours
Department
Pathology and Biomedical Science (Christchurch)
Supervisors
Dr Martina Paumann-Page, Professor Mark Hampton

Overview

New Zealand has one of the world’s highest cancer rates, one of them melanoma, which is an aggressive and treatment-resistant skin cancer, accounting for about 80 per cent of skin cancer deaths. Early detection of localised melanoma is critical and surgical excision is mostly curative. However, once metastatic, melanoma is notoriously difficult to treat with five-year survival rates of only about 20 per cent. Despite recent advances in targeted therapies and the development of checkpoint inhibitors, a better understanding of the underlying molecular mechanisms of melanoma progression are critically important for the development of novel therapeutic approaches.

There is increasing evidence that peroxidasin expression contributes to cancer cell invasion, a hallmark of tumour progression, and correlates with poor prognosis. However, the role that peroxidasin plays in cancer is currently unidentified. We and others have shown high expression of peroxidasin in invasive metastatic melanoma, which was also reported for ovarian, prostate, breast and brain cancer.

Our recent work on metastatic melanoma cells confirmed that peroxidasin expression is connected to the invasive phenotype, with low to non-detectable levels in non-invasive melanoma cells. Additionally, RNAseq data analysis identified peroxidasin as one of the most differentially expressed genes when comparing invasive with non-invasive melanoma cells, identifying peroxidasin as an important player in melanoma cell invasion. This suggests that peroxidasin may be an attractive diagnostic or prognostic target, which may also be exploited therapeutically, based on either peroxidasin inhibition or utilising peroxidasin for pro-drug activation. However, the evaluation of the mechanistic role of peroxidasin is paramount first.

Peroxidasin is an extracellular peroxidase enzyme which utilises hydrogen peroxide to oxidize bromide to hypobromous acid, a strong oxidant which reacts with a multitude of biomolecules. We hypothesize that peroxidasin is involved in cell signalling via the oxidants it generates, causing dysregulated oxidative modifications which increase proliferation, invasion and maladaptive cell signalling.

In this project we aim to identify if oxidants generated by peroxidasin are involved in pro-survival paracrine cell signalling by activating cell signalling pathways in melanoma cells and if this leads to increased proliferation. Cells will be cultured and treated with oxidants and changes in cell signalling pathways will be identified using Western blotting. Cell proliferation assays will be used to determine the effect of oxidants on cell growth, combining colorimetric and microscopy approaches.

Preferred student expertise:

We are looking for a bright and enthusiastic science or health science student with great attention to detail.

Further information:

This is one of a number of projects on offer for the 2022 intake of BBiomedSc(Hons) at the University of Otago, Christchurch campus.

Contact

Dr Martina Paumann-Page
Tel   +64 3 364 1559
Email   martina.paumann-page@otago.ac.nz