HYPOXIA AND CANCER
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, supervise DPhil students 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.
Hypoxia inducible factors regulate infectious SARS-CoV-2, epithelial damage and respiratory symptoms in a hamster COVID-19 model
Wing PAC. et al, (2022), PLOS Pathogens, 18, e1010807 - e1010807
Absolute quantitation of individual SARS-CoV-2 RNA molecules provides a new paradigm for infection dynamics and variant differences
Lee JY. et al, (2022), eLife, 11
Developmental role of PHD2 in the pathogenesis of pseudohypoxic pheochromocytoma.
Eckardt L. et al, (2021), Endocrine-related cancer, 28, 757 - 772
Hypoxia compromises the mitochondrial metabolism of Alzheimer’s disease microglia via HIF1
March-Diaz R. et al, (2021), Nature Aging, 1, 385 - 399
Hypoxic and pharmacological activation of HIF inhibits SARS-CoV-2 infection of lung epithelial cells
Wing PAC. et al, (2021), Cell Reports, 35, 109020 - 109020