Associate Professor Michelle Hill
|Associate Professor Michelle Hill|
With her experience in cell biology, biochemistry, proteomics and mass spectrometry, Associate Professor Michelle Hill is leading her team in two areas of translational cancer research. The clinical diagnostics team aims to develop new clinical tests for the management of cancer, including early detection, prognosis and personalized therapy selection. The cancer mechanisms team is dissecting the link between metabolism (obesity) and cancer, with current focus on the role of cholesterol-rich membrane microdomains in cancer spreading (metastasis).
Hill was an honours student at The University of Queensland (UQ) when a project in insulin signaling introduced her the ways cells use molecular signals for communication. Hooked, she pursued a PhD, then moved to Switzerland to work at the Friedrich Miescher Institute for Biomedical Research in order to further her understanding. There, she focused on a key cell signaling protein known to be dysregulated in diabetes and cancer, and discovered that it was regulated by a factor in lipid rafts. Lipid rafts are cell membrane microdomains enriched with a unique combination of lipids, cholesterol and proteins. Hill's discovery suggested that disturbances in lipid rafts could alter cell signaling, and thereby act as either disease triggers or enablers.
Following a subsequent post at Trinity College, Dublin, where she investigated the building blocks of a key protein complex involved in regulating cell death, Hill returned to Australia to work with Professors Rob Parton and John Hancock at UQ's Institute for Molecular Bioscience. Her focus turned to specialised 'flask-shaped' lipid rafts called caveolae. While it was known that a protein called caveolin-1 is crucial to caveolae formation and function in cell signaling, Hill discovered that a family of proteins, called PTRFs, are equally important.
"Two of the three PTRF family members had already been implicated in cancer, as was caveolin-1," explains Hill. "Our finding suggested a common link via lipid rafts in cancer development."
Seeking to translate her experience to benefit cancer patients, Hill obtained a highly competitive NHMRC Career Development Award to begin a research program to investigate the molecular mechanisms linking obesity and cancer, at the UQ Diamantina Institute in 2009. Together with the support of a Prostate Cancer Foundation Australia Young Investigator Award (2009-2012), her research initially focussed on the role of caveolae proteins and lipid rafts in prostate cancer. Her achievements have been further recognised by award of a prestigious ARC Future Fellowship in 2012, to utilise novel subcellular systems analysis in order to understand lipid raft function.
"We have found that altering lipid rafts not only changes the property of the cancer cell, it also changes molecules that are released by the cancer cells to influence their neighbours," she says.
This leads to changes in the microenvironment surrounding the tumour, and at distant sites where tumours may spread. A recent study from the Hill Group, published in Journal of Extracellular Vesicles demonstrate the functional effects of tumour-released small vesicles on bone cells, a common site of prostate cancer metastasis. As such, Hill's finding suggests that caveolae and lipid rafts are a good place to look for ways to block those signals for tumour spreading.
She believes this approach has broad potential across different cancer types despite the high diversity between them. "Many oncogenes and tumour suppressor gene functions are modulated by altering their location to lipid raft domains, while some may act by changing the lipid rafts themselves. I think it is likely that changes in lipid raft function may be a common event in cancer development and progression," she says.
In addition to searching for new cancer therapies, Hill also wants to improve clinical cancer management by developing new clinical tests. Her experience in biochemistry and proteomics (the large scale study of proteins) has been critical in the development of a new pipeline to discover and validate protein biomarkers.
"A biomarker is any molecule that indicates a disease state. We have developed a new method for finding and confirming new biomarkers for cancer, and we are planning to publish these seminal results very soon."
Using their novel method, the Hill Group has identified new blood biomarkers for oesophageal adenocarcinoma, a cancer of the oesophagus (gullet) with extremely poor survival rate. Working with colleagues from the UQ School of Veterinary Science, the team has also identified diagnostic biomarkers for canine haemangiosarcoma, a common cancer in dogs.
“We are working on clinical blood tests using these discovered biomarkers to improve the diagnosis of these deadly cancers.” With the excellent early results from their novel pipeline, Hill was successful in winning a National Breast Cancer Foundation grant in 2014 to apply the pipeline for breast cancer spreading biomarkers. Watch this space.
The clinical links between UQDI and the Princess Alexandra Hospital are crucial to Hill's work; collaborating clinicians inform her where their greatest diagnostic needs are and provide access to the tumours. Hill believes it's a good balance.
"They have the questions and the samples. We have the methods and technology. By working together, we hope to produce new clinical tests and therapies to combat cancer."
Telephone: +61 7 3443 7049
- Eunju Choi (past PhD student) - Anatomic Pathology Residency, Cornell University College of Veterinary Medicine, Ithaca, New York, USA
- Hyeongsun Moon (past PhD student) - Postdoctoral Fellow, Cornell University, Ithaca, New York, USA
- Dorothy Loo (past Masters student) - Proteomics & Mass Spectrometry Core Facility Manger, Translational Research Institute, Brisbane, Australia
- Dafydd Visscher (past Honours student) - pursuing MD/MSc degree at Utrecht University, The Netherlands
- Lara Petelin (past Honours student) - PhD student, University of Melbourne, Australia
- Kristine Hua (past Honours student) - PhD student, QIMR Berghofer Institute of Medical Research, Brisbane, Australia
Associate Professor Hill's interdisciplinary research in translational oncology focuses on two areas; (1) biomarker discovery and development into clinical tests, and (2) molecular mechanism of obesity on cancer development and progression, with current focus on cholesterol-rich membrane microdomains.
- Mechanisms underlying the beneficial effects of exercise in cancer prevention and treatment.
- Combined computational and experimental studies on the role of cholesterol in cancer progression.
- Clinical cancer diagnostic test development from biomarker discovery and validation using mass spectrometry techniques, clinical assay development and testing, to clinical studies using these biomarkers.
- Lipid raft-mediated regulation and function of tumour cell-derived extracellular vesicles (exosomes) in cancer