Dr Alan Harper

Title: Lecturer in Bioscience
Phone: +44 (0)1782 734654 or 674472
Email: a.g.s.harper@keele.ac.uk
Location: Institute for Science & Technology in Medicine, Keele University,
Guy Hilton Research Centre, Thornburrow Drive, Hartshill, Stoke-on-Trent, Staffordshire ST4 7QB United Kingdom

Role: ISTM Research theme: Therapeutics
Contacting me: By E-mail please
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I was appointed to a lecturer in biosciences in Keele at the end of 2010. Before arriving in Keele I obtained a first class BA(Hons) in Natural Sciences (specialising in Physiology in the final year) from Queens’ College, University of Cambridge. I was then awarded a British Heart Foundation PhD studentship to investigate the molecular mechanisms underlying the activation of store-operated calcium entry in human platelets in the Department of Physiology, Development and Neuroscience, University of Cambridge.  I completed my PhD in 2007 and was elected to a Junior Research Fellowship at St Catharine’s College, University of Cambridge in October of the same year. During my time at St Catharine’s, I was actively involved in both university and college teaching in physiology for medical, veterinary and natural science students, and In 2009, I was appointed as the Director of Studies for first year Preclinical medicine at St Catharine’s College.

ISTM Research theme: Therapeutics

My research interests lie in the calcium signalling mechanisms that control the activation and aggregation of human platelets in responses to physiological stimuli.  These calcium signals are crucial to allow platelets to clot upon damage to the blood vessel wall.  However platelets can also be triggered to clot inside intact, inflamed blood vessles.  This aberrant clotting can lead to a person suffering from deep vein thrombosis, pulmonary embolism, heart attack and stroke. These cardiovascular disorders are the main cause of death in adults in the United Kingdom. Therefore understanding the calcium signalling mechanisms of platelets may allow us to identify novel targets for drugs to help prevent this unwanted platelet activity.  

Calcium signalling is the result of a complex interplay between a number of direct and indirect factors that can affect the flux of calcium into and out of the cytosol, therefore solely interpreting data measuring the cytosolic calcium concentration can lead to incorrect conclusions to how this signal was brought about (Harper & Sage, 2007; Harper et al.,2009; Harper et al., 2010; Sage et al., 2011). Therefore my research has become interested in developing and utilising a systems-level analysis of platelet calcium signalling in which all the factors that can influence platelet cytosolic calcium concentration are systematically measured.  We believe this methodology will help us more reliably decode the mechanisms by which calcium signals are shaped in these cells. We want to develop this systems-level analysis further, and in the future we hope to use it to further delineate the calcium signalling system of platelets from healthy individuals, as well as to help identify areas of the calcium signalling system which are dysregulated in situations where platelet calcium signalling is known to be abnormal such as in patients suffering from diabetes mellitus, hypertension and stroke.

Selected Publications

  • Harper AGS. 2017. Platelet Signalling: Calcium. In Platelets in Thrombotic and Non-Thrombotic Disorders. Springer Link. doi> link>
  • Harper AGS and Sage SO. 2016. TRP-Na(+)/Ca(2+) Exchanger Coupling. (vol. 898). link> doi>
  • Koivula FNM, McClenaghan NH, Harper AGS, Kelly C. Islet-intrinsic effects of CFTR mutation. Diabetologia, vol. 59(7), 1350-1355. link> doi>
  • Musa F, Harper AGS, Yang Y. 2016. A real-time monitoring system to assess the platelet aggregatory capacity of components of a tissue-engineered blood vessel wall. Tissue Engineering Part C: Methods. doi>
  • Lever RA, Hussain A, Sun BB, Sage SO, Harper AGS. 2015. Conventional protein kinase C isoforms differentially regulate ADP- and thrombin-evoked Ca²⁺ signalling in human platelets. Cell Calcium, vol. 58(6), 577-588. link> doi> full text>

Full Publications List show

Journal Articles

  • Koivula FNM, McClenaghan NH, Harper AGS, Kelly C. Islet-intrinsic effects of CFTR mutation. Diabetologia, vol. 59(7), 1350-1355. link> doi>
  • Musa F, Harper AGS, Yang Y. 2016. A real-time monitoring system to assess the platelet aggregatory capacity of components of a tissue-engineered blood vessel wall. Tissue Engineering Part C: Methods. doi>
  • Lever RA, Hussain A, Sun BB, Sage SO, Harper AGS. 2015. Conventional protein kinase C isoforms differentially regulate ADP- and thrombin-evoked Ca²⁺ signalling in human platelets. Cell Calcium, vol. 58(6), 577-588. link> doi> full text>
  • Walford T, Musa FI, Harper AGS. 2016. Nicergoline inhibits human platelet Ca(2+) signalling through triggering a microtubule-dependent reorganization of the platelet ultrastructure. Br J Pharmacol, vol. 173(1), 234-247. link> doi> full text>
  • Sage SO, Jarvis GE, Jardín I, Rosado JA, Harper AGS. 2014. The TRPV1 ion channel is expressed in human but not mouse platelets. Platelets, vol. 25(5), 390-392. link> doi>
  • Sage SO, Pugh N, Farndale RW, Harper AGS. 2013. Pericellular Ca(2+) recycling potentiates thrombin-evoked Ca(2+) signals in human platelets. Physiol Rep, vol. 1(5), e00085. link> doi> full text>
  • Harper AGS, Pugh N, Farndale RW, Sage SO. 2011. Evidence for a role for the open canalicular system in generating pericellular ca(2+) signals in human platelets. JOURNAL OF THROMBOSIS AND HAEMOSTASIS, vol. 9, 309. link>
  • HARPER A. 2011. Monitoring the intracellular store Ca2+ concentration in agonist-stimulated, intact human platelets by using Fluo-5N. Journal of Thrombosis and Haemostasis, 540-551. doi>
  • Harper MT, Mason MJ, Sage SO, Harper AGS. 2010. Phorbol ester-evoked Ca2+ signaling in human platelets is via autocrine activation of P(2X1) receptors, not a novel non-capacitative Ca2+ entry. J Thromb Haemost, vol. 8(7), 1604-1613. link> doi>
  • 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, vol. 45(5), 413-420. link> doi>
  • Harper AGS, Brownlow SL, Sage SO. 2009. A role for TRPV1 in agonist-evoked activation of human platelets. J Thromb Haemost, vol. 7(2), 330-338. link> doi>
  • Harper AGS and 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, vol. 42(6), 606-617. link> doi>
  • Redondo PC, Harper AGS, Harper MT, Brownlow SL, Rosado JA, Sage SO. 2007. hTRPC1-associated alpha-actinin, and not hTRPC1 itself, is tyrosine phosphorylated during human platelet activation. J Thromb Haemost, vol. 5(12), 2476-2483. link> doi>
  • Redondo PC, Harper AGS, Sage SO, Rosado JA. 2007. Dual role of tubulin-cytoskeleton in store-operated calcium entry in human platelets. Cell Signal, vol. 19(10), 2147-2154. link> doi>
  • Harper AGS and Sage SO. 2007. A role for the intracellular protease calpain in the activation of store-operated calcium entry in human platelets. Cell Calcium, vol. 41(2), 169-178. link> doi>
  • Cauwenberghs S, Feijge MAH, Harper AGS, Sage SO, Curvers J, Heemskerk JWM. 2006. Shedding of procoagulant microparticles from unstimulated platelets by integrin-mediated destabilization of actin cytoskeleton. FEBS Lett, vol. 580(22), 5313-5320. link> doi>
  • Rosado JA, López JJ, Harper AGS, Harper MT, Redondo PC, Pariente JA, Sage SO, Salido GM. 2004. Two pathways for store-mediated calcium entry differentially dependent on the actin cytoskeleton in human platelets. J Biol Chem, vol. 279(28), 29231-29235. link> doi>
  • Redondo PC, Harper AGS, Salido GM, Pariente JA, Sage SO, Rosado JA. 2004. A role for SNAP-25 but not VAMPs in store-mediated Ca2+ entry in human platelets. J Physiol, vol. 558(Pt 1), 99-109. link> doi>
  • Brownlow SL, Harper AGS, Harper MT, Sage SO. 2004. A role for hTRPC1 and lipid raft domains in store-mediated calcium entry in human platelets. Cell Calcium, vol. 35(2), 107-113. link> doi>

Chapters

  • Harper AGS. 2017. Platelet Signalling: Calcium. In Platelets in Thrombotic and Non-Thrombotic Disorders. Springer Link. doi> link>
  • Harper AGS and Sage SO. 2016. TRP-Na(+)/Ca(2+) Exchanger Coupling. (vol. 898). link> doi>

I teach elements of the undergraduate curriculum for the Keele University MBChB in the School of Medicine.

Research Grants Held: 

British Heart Foundation Project Grant – Molecular and functional characterization of sodium-calcium exchangers and their role in secretion and calcium signaling in human platelets (PG/07/100/23759). Coheld with Dr Stewart Sage and Dr Michael Mason.