Dr Fiona Simpson

Australian born but growing up in Scotland, Dr Fiona Simpson intended to become a country vet, but was advised to get a biochemistry degree first. “After going to the local chemist to find out what biochemistry was, I enrolled and found I loved science. When I got my vet school offer, I turned it down and went to Cambridge to do my PhD instead,” she says.

Simpson was awarded a Wellcome Trust International Postdoctoral Fellowship to work with Professor Sandra Schmid, Chair of Cell Biology at the Scripps Institute in the US. Together they developed assays that enabled functional characterisation of novel proteins in endocytosis, the process by which cells internalise substances. She led a collaboration that determined the roles and functional stages of crucial endocytosis proteins, many of which are now known to be essential in neural signalling. Simpson then came to the University of Queensland (UQ) to work with Professor David James, where she further developed protein characterisation assays and expanded her expertise in cellular trafficking. She investigated the translocation mechanism of Glut4, the glucose transporter that responds to insulin, in order to identify ways to overcome insulin resistance in diabetes. As part of this work, she developed a plasma membrane purification method that is now widely used.

Following a Fellowship at UQ’s Institute for Molecular Bioscience, where she identified a novel protein in the skin’s UV-induced DNA-damage response, an opportunity arose to start her own research group at the UQ Diamantina Institute (UQDI).

“I began working on EGFR immediately,” says Simpson. EGFR is a cell surface receptor known to be integral in regulating numerous cellular functions and is a central molecule in tumourigenesis. In collaboration with oncologists at the Princess Alexandra Hospital (PAH), she demonstrated that both EGFR endocytosis and trafficking within the cell are dysregulated in Squamous Cell Carcinoma (SCC), the most common form of head and neck cancer.

The internalisation of cell surface receptors into cells, a process termed endocytosis, is a major mechanism for signalling regulation. We have assembled a number of reagents and constructs which allow us to hold receptors at various localisations on their trafficking itinerary in order to analyse the spatial regulation of signalling. We have a particular interest in the epidermal growth factor receptor (EGFR). EGFR is over-expressed in a number of tumors. EGFR inhibitors such as monoclonal antibodies targeting the extracellular domain of EGFR as well as small molecule inhibitors are used as a treatment option for various tumors. However, significant variance is found in patient responses to these treatments. We are investigating the role of EGFR trafficking in squamous cell carcinoma and its role in patient treatment responses.

There, she specialised in cellular trafficking and discovered a new protein complex integral to pigmentation: AP-3. “We were the first to describe how eye colour and coat colour in mice were melanosome trafficking mutations,” explains Simpson. “It opened up a new field.” It is now known that human mutations in AP-3 are involved in platelet deficiencies, albinism, melanoma biology, and synaptic vesicle formation in neurons.

Although anti-EGFR antibodies are used in SCC treatment, patient response varies widely. As such, Simpson’s group has developed an assay that determines whether EGFR trafficking dysregulation correlates with individual treatment responses. She explains that anti-EGFR therapy can have harsh side-effects so it’s important to know who will benefit and who won’t. She aims to develop a prognostic test for anti –EGFR therapy that will guide clinical decisions. “In the longer term,” she adds, “we hope to use our mechanistic information to increase responses to therapy and bypass resistance.” Access to clinicians, patients, and tumour samples are crucial to Simpson’s work. She explains that the biochemistry of a tumour changes rapidly once removed from the patient, so analysis within half-an-hour of removal is essential. The collaboration between UQDI and PAH enables this. Simpson believes her findings will have implications for numerous forms of cancer and is passionate about her work. “I have lost family members, including my mother, to cancer. Seeing the patients down in the clinics is also a driver. I love research and find it stimulating, and I enjoy teaching our next generation of research scientists.”