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Associate Professor of Cell Signalling
After graduating with a degree in Chemistry from the University of Oxford, I undertook a research project in the Ecuadorian rainforest. This was followed by work in the USA on how genes function in normal and diseased states, using the fruit fly as an in vivo model system. I was involved in investigating early embryonic patterning events and then the regulation of neuronal survival.
During my doctoral degree at the University of Kent, I continued to work with the fly model and developed an interest in the control of cell growth and its significance for cancer cells. My findings showed that the homologue of the major human tumour suppressor gene PTEN acts as a brake on the oncogenic PI3-kinase pathway. The giant cells observed in PTEN mutant tissue highlighted cell growth control as a central feature of cancer biology.
In my postdoctoral years, I focused on the regulation of the microenvironmental sensor mTORC1, which is a downstream target of PI3-kinase/PTEN and acts to co-ordinate growth and metabolism. Collaborative work revealed that members of the Proton-assisted Amino acid Transporter (PAT or solute carrier SLC36) family acted as growth promoters via their ability to signal as ‘transceptors’ that can regulate mTORC1 activity.
By 2005, I was running an independent research group to investigate the role of the PATs in cancer biology and tumour progression. My group is now working on a Cancer Research UK Programme investigating the links between amino acid sensing, changes in mTORC1 signalling and communication between cells involving small secreted vesicles known as exosomes, which can promote cancer progression. This work involves parallel analysis in human cancer cells and an in vivo fly cellular model of exosome secretion. DPhil students and our clinical collaborators are extending this research, through complementary studies on mechanisms involved in exosome regulation, using several cancer cell types. With support from the BBSRC, we are also undertaking related work, including the investigation of the cellular mechanisms leading to exosome heterogeneity. In 2016, I co-founded ‘Oxosome: the Oxford extracellular vesicle interest group’ to promote interactions between research groups working on extracellular vesicles,
In addition to undertaking research, I sit on the Cancer Research UK Oxford Centre Research Committee, teach courses for first and third year Medical and Biomedical Sciences undergraduate students and am involved in coordinating Public Engagement work for the department, as the academic Public Engagement Lead.
PAT4 levels control amino-acid sensitivity of rapamycin-resistant mTORC1 from the Golgi and affect clinical outcome in colorectal cancer.
Fan S-J. et al, (2016), Oncogene, 35, 3004 - 3015
Amino Acid Sensing by mTORC1: Intracellular Transporters Mark the Spot.
Goberdhan DCI. et al, (2016), Cell Metab, 23, 580 - 589
Fine-Tuning of PI3K/AKT Signalling by the Tumour Suppressor PTEN Is Required for Maintenance of Flight Muscle Function and Mitochondrial Integrity in Ageing Adult Drosophila melanogaster.
Mensah LB. et al, (2015), PLoS One, 10
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