Dr Fiona Simpson
Dr Fiona Simpson

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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.

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.

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.
 
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.”

 

Email: f.simpson@uq.edu.au
Telephone: +61 7 3443 6930

Recent Publications

  1. Pera, Elena, Kaemmerer, Elke, Milevskiy, Michael J. G., Yapa, Kunsala T. D. S., O'Donnell, Jake S., Brown, Melissa A., Simpson, Fiona, Peters, Amelia A., Roberts-Thomson, Sarah J. and Monteith, Gregory R. (2016) The voltage gated Ca2+-channel Cav3.2 and therapeutic responses in breast cancer. Cancer Cell International, 16 24: . doi:10.1186/s12935-016-0299-0
  2. Hazar-Rethinam, Mehlika, de Long, Lilia Merida, Gannon, Orla M., Boros, Samuel, Vargas, Ana Cristina, Dzienis, Marcin, Mukhopadhyay, Pamela, Saenz-Ponce, Natalia, Dantzic, Daniel D. E., Simpson, Fiona and Saunders, Nicholas A. (2015) RacGAP1 is a novel downstream effector of E2F7-dependent resistance to doxorubicin and is prognostic for overall survival in squamous cell carcinoma. Molecular Cancer Therapeutics, 14 8: 1939-1950. doi:10.1158/1535-7163.MCT-15-0076
  3. Daniel, James A., Chau, Ngoc, Abdel-Hamid, Mohammed K., Hu, Lingbo, von Kleist, Lisa, Whiting, Ainslie, Krishnan, Sai, Maamary, Peter, Joseph, Shannon R., Simpson, Fiona, Haucke, Volker, McCluskey, Adam and Robinson, Philip J. (2015) Phenothiazine-derived antipsychotic drugs inhibit dynamin and vlathrin-mediated endocytosis. Traffic, 16 6: 635-654. doi:10.1111/tra.12272
  4. Jung, Ji-Won, Overgaard, Nana H., Burke, Michael T., Isbel, Nicole, Frazer, Ian H., Simpson, Fiona and Wells, James W. (2015) Does the nature of residual immune function explain the differential risk of non-melanoma skin cancer development in immunosuppressed organ transplant recipients?. International Journal of Cancer, . doi:10.1002/ijc.29450
  5. Hazar-Rethinam, Mehlika, Merida De Long, Lilia, Gannon, Orla M., Topkas, Eleni, Boros, Samuel, Vargas, Ana Cristina, Dzienis, Marcin, Mukhopadhyay, Pamela, Simpson, Fiona, Endo-Munoz, Liliana and Saunders, Nicholas A. (2015) A novel E2F/sphingosine kinase 1 axis regulates anthracycline response in squamous cell carcinoma. Clinical Cancer Research, 21 2: 417-427. doi:10.1158/1078-0432.CCR-14-1962
  6. Freeman, Andrew, Bridge, Jennifer A., Maruthayanar, Pirashanthini, Overgaard, Nana H., Jung, Ji-Won, Simpson, Fiona, Prow, Tarl W., Soyer, H. Peter, Frazer, Ian H., Freeman, Michael and Wells, James W. (2014) Comparative Immune Phenotypic Analysis of Cutaneous Squamous Cell Carcinoma and Intraepidermal Carcinoma in Immune-Competent Individuals: Proportional Representation of CD8+ T-Cells but Not FoxP3+ Regulatory T-Cells Is Associated with Disease Stage. PLoS One, 9 10: e110928.1-e110928.9. doi:10.1371/journal.pone.0110928
  7. Foote, M. C., McGrath, M., Guminski, A., Hughes, B. G. M., Meakin, J., Thomson, D., Zarate, D., Simpson, F. and Porceddu, S. V. (2014) Phase II study of single-agent panitumumab in patients with incurable cutaneous squamous cell carcinoma. Annals of Oncology, 25 10: 2047-2052. doi:10.1093/annonc/mdu368
  8. Gaffney, Daniel C., Soyer, H. Peter and Simpson, Fiona (2014) The epidermal growth factor receptor in squamous cell carcinoma: an emerging drug target. Australasian Journal of Dermatology, 55 1: 24-34. doi:10.1111/ajd.12025
  9. Hill, Michelle M., Daud, Noor Huda, Aung, Cho Sanda, Loo, Dorothy, Martin, Sally, Murphy, Samantha, Black, Debra M., Barry, Rachael, Simpson, Fiona, Liu, Libin, Pilch, Paul F, Hancock, John F., Marie-Odile Parat and Parton, Robert G. (2012) Co-regulation of cell polarization and migration by caveolar proteins PTRF/cavin-1 and caveolin-1. PLoS One, 7 8: e43041.1-e43041.9. doi:10.1371/journal.pone.0043041
  10. Saunders, Nicholas A., Simpson, Fiona, Thompson, Erik W., Hill, Michelle M., Endo-Munoz, Liliana, Leggatt, Graham, Minchin, Rodney F. and Guminski, Alexander (2012) Role of intratumoural heterogeneity in cancer drug resistance: Molecular and clinical perspectives. EMBO Molecular Medicine, 4 8: 675-684. doi:10.1002/emmm.201101131

 

  • Spatio-temporal signalling of the epidermal growth factor receptor and insulin receptor.
  • EGFR trafficking in squamous cell carcinoma and effects on Cetuximab treatment.