Research Interests

Biomarkers of tumour development and the response to chemotherapy in triple-negative breast cancer (TNBC)

• The bottom line. TNBC is an unpredictable type of breast cancer that is defined by negative diagnostic tests for hormone receptor levels and HER2 gene amplification. These tumours do not respond to classical breast cancer drugs that target hormone dependence (e.g., tamoxifen) or the HER2 protein (e.g., trastuzumab), leaving chemotherapy as the only option for systemic treatment in most cases. Another dilemma for this group is that it is still not possible to predict which patients will be amongst the 60 per cent of ‘responders’, and which patients are unlikely to have a lasting response. So, despite enduring the toxicity and fatigue of chemotherapy, some patients relapse within a few years anyway, with disease spreading to critical organs like the liver, lungs, and/or brain. This advanced stage of disease (stage IV) is very difficult to control, and usually leads to death within months or years.
• The details. Using tumour tissue donated by Brisbane breast cancer patients, along with published breast tumour genetic data, my work involves correlating simple or complex tumour traits with biological features and treatment outcomes. Previously, I explored the potential clinical significance of single proteins, groups of proteins, and hub genes identified through mathematical modelling of transcriptional networks in TNBC. My work with Mater Research involves trying to elucidate how epigenetic mechanisms confer plasticity and resilience to the TNBC genome, how this knowledge could be exploited to improve the prescription of chemotherapy, and whether certain epigenetic features can be therapeutically targeted to improve chemotherapy response.

Developing innovative therapeutics to prevent or treat brain metastases 

• The bottom line. Breast cancer that spreads to the brain is a serious complication that produces neurological side-effects and a significant decline in quality-of-life. Brain metastases are becoming increasingly common in advanced breast cancer because after spreading and establishing new ‘colonies’ within normal brain tissue, breast cancer tends to be quite resistant to existing treatments. In the early stages of cancer spread, the brain provides a sanctuary for microscopic clusters of tumour cells, protecting them from circulating drugs. In larger, symptomatic brain metastases, research indicates that blood flow is particularly sluggish, slowing down the delivery of systemic drug therapies. We need new, innovative ways to treat brain metastases, preferably when they are still small.
• The details. In collaboration with experts in immuno-oncology, radiotherapy, and engineered biologic therapies, I am exploring ways to reactivate tumour immunity in metastatic patients with brain involvement. This can involve administering a semi-tailored, exogenous vaccine; or engineered nano-carriers that deliver an immunogenic payload directly to the tumour. This is an ambitious approach that aims to achieve sustained intracranial treatment efficacy, with minimal or no side-effects.

Available PhD projects

Development of new theranostic agents for metastatic breast cancer surveillance and treatment

Most of the time, treatments for early breast cancer successfully prevent metastatic spread, but 10% of Australian patients still develop lethal recurrences within 5 years. Rather than waiting to see which patients develop symptoms of a possible relapse (e.g., headaches, respiratory symptoms), we are getting better at detecting metastasis early. Patients deemed to be at ‘high risk’ are offered regular PET or MRI scans, allowing earlier intervention and better quality-of-life. PET imaging of radioactive tracers is more specific than MRI, but the standard tracer used in oncology – [18F]fluorodeoxyglucose (FDG) – is not useful for imaging the brain. We are seeking a student to help us develop agents that seek out tumour cells more specifically than FDG and can also be engineered to function as therapeutics. The project is flexible depending on the successful candidate’s expertise and interest (e.g., in-vivo models of metastatic breast cancer, protein chemistry and/or molecular biology).