Higher Degree by Research Application Portal

Background  

Mesothelioma is a rare and aggressive cancer with limited treatment options and poor survival outcomes. Although treatments designed to activate the immune system against cancer have demonstrated some clinical benefit, the majority of mesothelioma patients fail to respond. 

Emerging evidence implicates copper as a critical factor in tumour progression. Copper accumulates in mesothelioma tissue, where it promotes tumour growth, immune evasion, and resistance to chemotherapy. Drugs that bind and reduce copper levels (copper chelators) are already approved for non-cancer indications, offering a unique opportunity for drug repurposing. 

This project will explore how manipulating copper availability affects tumour cell behaviour, immune cell function, and overall treatment response. Our goal is to determine whether copper chelation can improve the efficacy of standard therapies and immune-based treatments in mesothelioma. 

Aims 

• Investigate copper levels alters tumour cell behaviour and gene expression, including chemotherapy transporters, MHC-I, and PD-L1.
• Examine how copper affects tumour cell sensitivity to chemotherapy.
• Assess the impact of copper on immune cell function and tumour visibility using in vitro T cell–tumour cell killing assays. 
• Characterise how copper chelation therapy modulates immune cell composition and activity within the tumour microenvironment. 
• Evaluate the in vivo effectiveness of copper chelation therapy, alone or in combination with chemotherapy and/or immunotherapy, and its impact on the tumour microenvironment. 
• Use CRISPR-Cas9 to knock out key copper transporter genes in tumour and immune cells to dissect their role in treatment response. 
• Analyse publicly available datasets to investigate expression of copper-regulatory genes in cancer patients and correlate these with clinical outcomes and treatment responses. 

Outcomes 

Chance to travel to Sydney to work with UNSW collaborators. 

Multiple funding sources from Cancer Council WA, WA Department of Health.

Dr Jonathan Chee

jonathan.chee@uwa.edu.au, Institute for Respiratory Health

Kofi Stevens

Kofi.stevens@uwa.edu.au, Institute for Respiratory Health