Tom Keeley
Junior Research Fellow (Post-doctoral)
Research Interest
Mammals have evolved complex mechanisms to sense and respond to changes in oxygenation on a variety of different time scales, ranging from seconds to thousands of years. Adaptation to a hypoxic environment occurs within 24 hours of exposure and is coordinated by the hypoxia-inducible factor (HIF) transcription factors. Preceding this are a range of ‘reactive’ responses to hypoxia which, although well-grounded in physiology, are generally poorly understood at a molecular level. My work seeks to understand the biochemistry and physiology of acute and short-term cellular and organismal responses to hypoxia, focusing on two main areas: (i) rapid electrophysiological responses in specialised O2 sensing cell types, and (ii) control of G-protein signalling by via ADO-dependent proteasomal regulation. I employ a range of biochemistry, molecular biology and physiological techniques to study these processes in cultured cells and in isolated tissues ex vivo.
Background
I received a B.Sc. in Physiology from King’s College London, where I then undertook a Ph.D with Prof. Giovanni Mann exploring responses to low O2 conditions in endothelial cells. After a brief post-doc at KCL, I joined the Ratcliffe Lab in 2018 to work on novel hypoxia signalling pathways. In 2020 I took up a Junior Research Fellowship in medical sciences at St. Catherine’s College.
Recent publications
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Comparative analysis of N-terminal cysteine dioxygenation and prolyl-hydroxylation as oxygen-sensing pathways in mammalian cells
Journal article
Tian Y-M. et al, (2023), Journal of Biological Chemistry, 105156 - 105156
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Monitoring ADO dependent proteolysis in cells using fluorescent reporter proteins.
Chapter
Smith E. and Keeley TP., (2023), 686, 267 - 295
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The developmental role of PHD2 in the pathogenesis of pseudohypoxic PPGLs
Conference paper
Prange-Barczynska M. et al, (2022), ACTA PHYSIOLOGICA, 236, 25 - 25
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Nrf2-regulated redox signaling in brain endothelial cells adapted to physiological oxygen levels: Consequences for sulforaphane mediated protection against hypoxia-reoxygenation.
Journal article
Warpsinski G. et al, (2020), Redox biology, 37
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Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants
Journal article
Masson N. et al, (2019), Science, 365, 65 - 69