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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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
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Defining Physiological Normoxia for Improved Translation of Cell Physiology to Animal Models and Humans.
Journal article
Keeley TP. and Mann GE., (2019), Physiological reviews, 99, 161 - 234
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Reduced SERCA activity underlies dysregulation of Ca2+ homeostasis under atmospheric O2 levels.
Journal article
Keeley TP. et al, (2018), FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 32, 2531 - 2538