Junior Research Fellow (Post-doctoral)
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.
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.
Comparative analysis of N-terminal cysteine dioxygenation and prolyl-hydroxylation as oxygen-sensing pathways in mammalian cells
Tian Y-M. et al, (2023), Journal of Biological Chemistry, 105156 - 105156
Monitoring ADO dependent proteolysis in cells using fluorescent reporter proteins.
Smith E. and Keeley TP., (2023), 686, 267 - 295
The developmental role of PHD2 in the pathogenesis of pseudohypoxic PPGLs
Prange-Barczynska M. et al, (2022), ACTA PHYSIOLOGICA, 236, 25 - 25
Nrf2-regulated redox signaling in brain endothelial cells adapted to physiological oxygen levels: Consequences for sulforaphane mediated protection against hypoxia-reoxygenation.
Warpsinski G. et al, (2020), Redox biology, 37
Defining Physiological Normoxia for Improved Translation of Cell Physiology to Animal Models and Humans.
Keeley TP. and Mann GE., (2019), Physiological reviews, 99, 161 - 234