Research
My work focuses on intracellular calcium signalling mechanisms and the roles of calcium signals in platelet function. Much of my work has concerned the mechanisms which generate calcium entry and in particular on the mechanisms which couple the depletion of the intracellular calcium stores to the activation of calcium entry. This work employs fluorescent indicators and protein chemistry. Most recently, working with Dr Alan Harper (a former Research Fellow in my lab and now at the Institute for Science and Technology in Medicine, Keele University), I have been studying platelet calcium signalling at a systems level by investigating agonist-evoked changes in the concentration of calcium and ions which influence calcium movements, in various cellular and pericellular compartments. This work has revealed a calcium recycling system in platelets that appears to involve nanojunctions between the dense tubular system and open canalicular system at the platelet membrane complex.
Collaborators
Dr Alan Harper (Institute for Science and Technology in Medicine, Keele University)
Dr Gavin Jarvis (PDN)
Dr Mike Mason (PDN)
Prof Richard Farndale (Department of Biochemistry, University of Cambridge)
Dr Nick Pugh (Department of Life Sciences, Anglia Ruskin University, Cambridge)
Dr Juan Rosado and colleagues (Department of Physiology, University of Extremadura, Spain)
Publications
Sage SO, Jarvis GE, Jardín I, Rosado JA, Harper AGS, (2014), The TRPV1 ion channel is expressed in human but not mouse platelets, Platelets, 25, 390-392
Sage SO, Pugh N, Farndale RF, Harper AGS, (2013), Pericellular Ca2+ recycling potentiates thrombin-evoked Ca2+ signals in human platelets, Physiological Reports, 1, e00085
Sage SO, Pugh N, Mason MJ, Harper AGS, (2011), Monitoring the intracellular store Ca2+ concentration in agonist-stimulated, intact human platelets using Fluo-5N, Journal of Thrombosis and Haemostasis, 9, 540-551
Harper MT, Mason MJ, Sage SO, Harper AGS, (2010), Phorbol ester-evoked Ca signaling in human platelets is via autocrine activation of P receptors, not a novel non-capacitative Ca entry, Journal of Thrombosis and Haemostasis, 8, 1604-13
Harper MT, Sage SO, (2010), Src family tyrosine kinases activate thrombin-induced non-capacitative cation entry in human platelets, Platelets, 21, 445-450
Harper AGS, Brownlow SL, Sage SO, (2009), A role for TRPV1 in agonist-evoked activation of human platelets, Journal of Thrombosis and Haemostasis, 7, 330-339
Harper AGS, Mason MJ, Sage SO, (2009), A key role for dense granule secretion in potentiation of the Ca2+ signal arising from store-operated calcium entry in human platelets, Cell Calcium, 45, 413-420
Gilio K, Munnix IC, Mangin P, Cosemans JM, Feijge MA, van der Meijden PE, Olieslagers, Chrzanowska-Wodnicka MB, Lillian R, Schoenwaelder S, Koyasu S, Sage SO, Jackson SP, Heemskerk JWM, (2009), Non-redundant Roles of Phosphoinositide 3-Kinase Isoforms alpha and beta in Glycoprotein VI-induced Platelet Signaling and Thrombus Formation, Journal of Biological Chemistry, 284, 33750-33762
Harper MT, Sage SO, (2008), Is calcium-independent phospholipase A2 required for store-operated calcium entry in human platelets? Journal of Thrombosis and Haemostasis, 6, 1819-1821
Harper AGS, Sage SO, (2007), A role for the intracellular protease calpain in the activation of store-operated calcium entry in human platelets, Cell Calcium, 41, 169-178
Harper AGS, Sage SO, (2007), A key role for reverse Na+ /Ca2+ exchange influenced by the actin cytoskeleton in store-operated Ca2+ entry in human platelets: Evidence against the de novo conformational coupling hypothesis, Cell Calcium, 42, 606-617
Redondo PC, Harper MT, Rosado JA, Sage SO, (2006), A role for cofilin in the activation of store-operated calcium entry by de novo conformational coupling in human platelets, Blood, 107, 973-979
Teaching and Supervisions
Course Organiser, Part II PDN and Part II BBS PDN
Lecturer in Part II PDN Modules P1 (Cellular Physiology- Calcium Signalling) and P8 (Systems & Clinical Physiology – Renal Physiology), NST Part IB Physiology (Renal Physiology & Body Fluid Homeostasis), MVST Part IA (Body Fluid Homeostasis) and NST Part IA Physiology of Organisms (Osmoregulation in Animals).
