My research interests are in understanding the role of hypoxia in cancer. Specifically, we are interested in defining the circumstances and molecular pathways by which hypoxia and hypoxia signalling directly promote cell proliferation. Genetic mutations of hypoxia/HIF signalling pathway components are commonly associated with certain types of cancer e.g. carotid body paragangliomas, adrenal medullary pheochromocytomas, kidney clear cell carcinomas and understanding the mechanisms involved may help with treatment of these cancers. We have shown that Type I cells in the carotid body proliferate in response to hypoxia and that this (like VHL-associated kidney cancer) is dependent on a specific isoform of HIF, HIF-2alpha (Fielding et al., 2018; Hodson et al., 2016). Further, we have shown that unrestrained activation of HIF-2alpha in the mouse carotid body leads to a paraganglioma-like growth (Fielding et al., 2018), mimicking the human genetic condition and providing the first such mouse model to explore the mechanisms and potential therapeutic treatments of this and other HIF-2 dependent cancers.
I read Natural Sciences at Trinity Hall, Cambridge University followed by a PhD at Cambridge University in mitochondrial bioenergetics with Professor Martin Brand. I subsequently came to Oxford as a postdoctoral research scientist to study hypoxia/HIF signalling with Professor Sir Peter Ratcliffe. I currently head a group investigating the role of HIF-2 in hypoxic responses of the carotid body and lecture undergraduate medical students at Oxford about the HIF pathway.
I am actively involved in public engagement, for example, giving academic talks to secondary school students as part of Magdalen College, Oxford’s outreach programme.
Systemic silencing of HIF hydroxylase PHD2 causes reversible immunoregulatory dysfunction
YAMAMOTO A. et al, (2019), Journal of Clinical Investigation
PHD2 inactivation in Type I cells drives HIF-2α-dependent multilineage hyperplasia and the formation of paraganglioma-like carotid bodies.
Fielding JW. et al, (2018), J Physiol
Hypoxia-inducible factor 1-alpha does not regulate osteoclastogenesis but enhances bone resorption activity via prolyl-4-hydroxylase 2.
Hulley PA. et al, (2017), J Pathol, 242, 322 - 333
How does hypoxia-inducible factor (HIF) regulate osteoclastogenesis and bone erosion?
Knowles HJ. et al, (2016), Frontiers in Endocrinology: Bone Research
Regulation of ventilatory sensitivity and carotid body proliferation in hypoxia by the PHD2/HIF-2 pathway.
Hodson EJ. et al, (2016), J Physiol, 594, 1179 - 1195