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Dr Emma Veale

Research Associate

Medway School of Pharmacy

 

Emma studied biochemistry at Brunel University in West London during which she obtained her first publication. After obtaining her degree she joined Imperial College London as a research technician, working initially in plant research (with the late Dr Gary Warren) as a molecular biologist. Emma then moved into the labs of Professor Brian Robertson and Professor Alistair Mathie as a research assistant, studying the role of mammalian ion channels in neurons, where she combined her molecular biology skills with patch-clamp electrophysiology. In May 2007, she relocated with Professor Mathie to take up her current position as a research associate in the Biological Sciences Group within the Medway School of Pharmacy, where she obtained her PhD by published works.

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Emma’s main research focus has been primarily to understand the role of two-pore domain potassium (K2P) ion channels in controlling the excitability and firing of mammalian cells, particularly neurons. In particular, their regulation by various pharmacological agents, physiological mediators and neurotransmitter substances, using whole-cell patch clamp electrophysiology.

As well as studying the structural, functional and expression properties of these K2P channels, they have a major interest in investigating the role of K2P’s in a range of diverse physiological and pathophysiological conditions, including depression, pain, KCNK9 imprinting syndrome – Birk Barel and Balkan Endemic Nephropathy, which has led to publications in high impact journals (see publication list for more details). Emma is a joint editor with Professor Alistair Mathie and other colleagues of the Concise Guide to Pharmacology.

A number of the labs research projects are also carried out in collaboration with the pharmaceutical industry (LifeArc, Pfizer, Takeda, Galleon) and academic laboratories in the UK, Austria, Germany, USA and Australia.

Currently, we have a major project investigating the mutations in TASK-3 two pore domain potassium (K2P) channels, responsible for KCNK9 imprinting syndrome.  Through clinical collaborators across the world, we are continually informed of new patients with mutations of KCNK9 (TASK-3). About half of these have the same “G236R” mutation as patients originally documented with this syndrome. However, there are now many other mutations identified in different regions of the TASK-3 channel. Two major complications have arisen from this. Firstly, the symptoms displayed by the patients vary quite widely both in their phenotype and in their intensity.

Secondly, some of the mutations do not lead to the same functional alterations in the TASK-3 channel. As such, compounds which activate TASK-3 channels, a suggested therapy for the original patient cohort, may not be efficacious in all patients. At present, together with many colleagues around the world, we are trying to collate the information we have, both in terms of the patients and the properties of the mutated channels, to build as complete a picture as possible of this syndrome, its consequences and its potential treatment. As a direct result of this work, one activator has been adopted in a trial by some patients for use in the treatment of “KCNK9 imprinting syndrome”, a disease resulting from the mutation of the K2P channel, TASK3 (KCNK9, K2P9.1). Because of the diverse physiology of these channels they represent major potential therapeutic targets for current and future research. Emma has developed strong collaborate links with clinicians at the Mayo Clinic, Rochester, MN and Cedars-Sinai Medical centre, Los Angeles, CA. Along with her collaborators, Emma is a moderator of the KCNK9 gene, on the Human Disease Genes Website.

In addition, in the area of K2P channels, we have projects on the role and therapeutic importance of TASK-1 channels in pulmonary hypertension (with Dr Angel Cogolludo and colleagues in Madrid) and, more generally, on the role of infection in pulmonary hypertension as part of an international consortium led by our colleagues Professor Ghazwan Butrous and Professor Sir Magdi Yacoub.

In a separate K2P channel project, we have just begun a formal, funded collaboration with Dr Paul Wright and colleagues at LifeArc Centre for Therapeutics Discovery to investigate novel K2P channel activators for the alleviation of pain

More recently Emma has extended her research interests into practice-based research to look at the detection of atrial fibrillation (AF) in primary care by clinical pharmacists and the development of novel approaches using AI to improve AF screening and detection, supported, primarily, by Bayer. This project was the recent recipient of a 2019 Healthcare Pioneers award from the Atrial Fibrillation Association and has been shortlisted for Excellence in General Practice Pharmacy award at the 8th edition of the Clinical Pharmacy Congress, taking place on the 7th-8th  in June 2019 at ExCeL London. Emma has created strong collaborative links in primary and secondary care and works closely with the cardiologist, Dr Adrian Stewart based at Medway Maritime Hospital.

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Recent Publications

  • Cunningham KP, Holden RG, Escribano-Subias P, Cogolludo A, Veale EL, Mathie A (2019). Characterisation and regulation of wild type and mutant TASK-1 two pore domain potassium channels indicated in pulmonary arterial hypertension. J Physiol 597: 1087-1101.
  • Veale EL, Stewart AJ, Mathie A, Lall SK, Rees-Roberts M, Savickas V, Bhamra SK, Corlett SA (2018). Pharmacists Detecting Atrial Fibrillation (PDAF) in primary care during the flu vaccination season: a multi-site, cross-sectional screening protocol BMJ Open 8(3): e021121. 
  • Fernández-Fernández D, Cadaveira-Mosquera A, Rueda-Ruzafa L, Herrera-Pérez S, Veale EL,Reboreda A, Mathie A, Lamas JA (2018) Activation of TREK currents by riluzole in three subgroups of cultured mouse nodose ganglion neurons. PLOS ONE 13(6):e0199282.
  • Loucif A, Saintot P-P, Liu J, Antonio BM, Zellmer SG, Yoger K, Veale EL, Wilbrey A, Omoto K, Cao L, Gutteridge A, Castle NA, Stevens EB, Mathie A (2018). GI-530159, a novel, selective, mechano-sensitive two-pore-domain potassium (K2P) channel opener, reduces rat dorsal root ganglion (DRG) neuron excitability. Br J Pharmacol 175: 2272-2283. 
  • Olschewski A, Veale EL, Nagy BM, Nagaraj C, Kwapiszewska G, Antigny F, Lambert M, Humbert M, Czirjak G, Enyedi P, Mathie A (2017). TASK-1 (KCNK3) channels in the lung: from cell biology to clinical implications. European Respiratory Journal 50 (5): 1700754.
  • Wright PD, Veale EL, McCoull D, Large J, Tickle D, Gothard G, Ococks E, Kettleborough C, Mathie A, Jerman J (2017). Terbinafine is a novel and selective activator of the two-pore domain potassium channel TASK3. Biochemical and Biophysical Research Communications  493: 444-450.
  • Veale EL, Mathie A (2016) Aristolochic acid, a plant extract used in the treatment of pain and linked to Balkan Endemic Nephropathy, is a regulator of K2P channels.  Br. J. Pharmacol 173: 1639-1652.
  • Mathie A, Veale EL (2015). Two-pore domain potassium channels: Potential therapeutic targets for the treatment of pain. Pflug Arch Eur J Physiol. 467, 5, 931-943
  • Veale EL, Al Moubarak E, Bajaria N, Omoto K, Cao L, Tucker SJ, Stevens EB, Mathie A (2014). Influence of the N-terminus on the Biophysical Properties and Pharmacology of TREK1 Potassium Channels. Mol Pharmacol doi:10.1124/mol.113.091199.
  • Veale EL, Al Moubarak E, Bajaria N, Omoto K, Cao L, Tucker SJ, Stevens EB, Mathie A (2014). Influence of the N-terminus on the Biophysical Properties and Pharmacology of TREK1 Potassium Channels. Mol Pharmacol 85: 671-681.
  • Veale EL, Hassan M, Walsh Y, Al Moubarak E, Mathie A (2014). Recovery of current through mutated TASK3 potassium channels underlying Birk Barel syndrome. Mol Pharmacol 85: 397-407.
  • El Hachmane MF, Rees KA, Veale EL, Sumbayev VV, Mathie A (2014). Enhancement of TWIK-related acid sensitive potassium channel 3 (TASK3) two pore domain potassium channel activity by TNFa. J Biol Chem 289: 1388-1401.

Full List of Refereed Papers

  • Veale EL, Rees KA, Mathie A, Trapp S (2010). Dominant negative effects of a non-functional TREK1 splice variant expressed in brain. J Biol Chem 285: 29295-29304.
  • Mathie A, Al Moubarak E, Veale EL (2010). Gating of two pore domain potassium channels. J Physiol 588: 3149-3156.
  • Mathie A, Rees KA, El Hachmane MF, Veale EL (2010). Trafficking of neuronal two pore domain potassium channels. Curr Neuropharmacol 8: 276-286.
  • Cao L, Veale EL, Mathie A, Stevens E (2010). Differential modulation of TREK-1, TASK-3 and TRESK K2P ion channels by BL-1249. Program No. 174.6/KK13. 2010 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2010. Online.
  • Rees KA, Veale EL, Mathie A (2010). Stimulation of heteromeric TASK channel trafficking by 14-3-3(beta) protein. Basic and Clinical Pharmacology & Toxicology 107 (Suppl. 1), 119.
  • Clarke CE, Veale EL*, Wyse K, Vandenberg JI, Mathie A (2008). The M1P1 loop of TASK3 K2P channels apposes the selectivity filter and influences channel function. J Biol Chem 283: 16985-16992. * joint first author.
  • Mathie A, Veale EL (2008). Neuronal Potassium Channels. In Encyclopedia of Neuroscience: 2792-2797. eds. Binder M, Hirokawa N, Windhorst U, Hirsch MC, Springer-Verlag (Berlin).
  • Veale EL, Aller MI, Mathie A (2008). Functional characteristics and regulation of mouse THIK1 two-pore-domain potassium channels. Acta Physiol Sinica 60 S1: 229.
  • Veale EL, Buswell R, Clarke CE, Mathie A (2007). Identification of a region in the TASK3 two pore domain potassium channel that is critical for its blockade by methanandamide. Br J Pharmacol 152: 778-786.
  • Brickley SG, Aller MI, Sandu C, Veale EL, Alder FG, Sambi H, Mathie A, Wisden W (2007). TASK-3 two-pore domain potassium channels enable sustained high-frequency firing in cerebellar granule neurons. J Neurosci 27: 9329-9340.
  • Mathie A, Veale EL (2007). Therapeutic potential of neuronal two pore domain potassium channel modulators. Curr Opin Invest Drugs 8: 555-562.
  • Veale EL, Kennard LE, Sutton GL, MacKenzie G, Sandu C, Mathie A (2007). G(alpha)q mediated regulation of TASK3 two pore domain potassium channels: the role of protein kinase C. Mol Pharmacol 71: 1666-1675.
  • Veale EL, Buswell R, Clarke CE, Mathie A (2007). Identification of a region in the TASK3 two pore domain potassium channel that is critical for its blockade by methanandamide. Brit J Pharmacol advanced online publication doi:10.1038/sj.bjp.0707436.
  • Brickley SG, Aller MI, Sandu C, Veale EL, Alder FG, Sambi H, Mathie A, Wisden W (2007). TASK-3 two-pore domain potassium channels enable sustained high-frequency firing in cerebellar granule neurons. J Neurosci 27:9329-9340.
  • Mathie A, Veale EL (2007). Therapeutic potential of neuronal two-pore domain potassium-channel modulators. Curr Opin Investig Drugs 8:555-562.
  • Veale EL, Kennard LE, Sutton GL, MacKenzie G, Sandu C, Mathie A (2007). G(alpha)q-mediated regulation of TASK3 two-pore domain potassium channels: the role of protein kinase C. Mol Pharmacol 71:1666-1675.
  • Mathie A, Sutton GL, Clarke CE, Veale EL (2006). Zinc and copper: pharmacological probes and endogenous modulators of neuronal excitability. Pharmacol Ther 111:567-583.
  • Linden AM, Aller MI, Leppa E, Vekovischeva O, Aitta-Aho T, Veale EL, Mathie A, Rosenberg P, Wisden W, Korpi ER (2006). The contributions of TASK-1-containing channels to the actions of inhalation anesthetics, the alpha(2) adrenergic sedative dexmedetomidine, and cannabinoid agonists. J Pharmacol Exp Ther 317:615-626.
  • Aller MI, Veale EL, Linden AM, Sandu C, Schwaninger M, Evans LJ, Korpi ER, Mathie A, Wisden W, Brickley SG (2005). Modifying the subunit composition of TASK channels alters the modulation of a leak conductance in cerebellar granule neurons. J Neurosci 25:11455-11467.
  • Kennard LE, Chumbley JR, Ranatunga KM, Armstrong SJ, Veale EL, Mathie A (2005). Inhibition of the human two-pore domain potassium channel, TREK-1, by fluoxetine and its metabolite norfluoxetine. Br J Pharmacol 144:821-829.
  • Clarke CE, Veale EL, Green PJ, Meadows HJ, Mathie A (2004). Selective block of the human 2-P domain potassium channel, TASK-3, and the native leak potassium current, IKSO, by zinc. J Physiol 560:51-62.
  • Mathie A, Clarke CE, Ranatunga KM, Veale EL (2003). What are the roles of the many different types of potassium channel expressed in cerebellar granule cells? Cerebellum 2:11-25.

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Refereed Conference Contributions

  • Veale EL, Mathie A (2015) Aristolochic acid, a plant extract used in the treatment of pain, is a potent regulator of K2P channels. Proceedings of the British Pharmacological Society, www.pA2online.org/abstracts/vol13 in press.
  • Mathie A, Veale EL (2015) A mutation of TASK2 K2P channels (T108P), found in certain patients predisposed to Balkan Endemic Nephropathy, reduces TASK2 current density and alters ion selectivity. Proceedings of the British Pharmacological Society, www.pA2online.org/abstracts/vol13 in press.
  • Loucif AJ, Saintot P-P, Liu J, Antonio BM, Zellmer SG, Veale EL, Mathie A, Cao L, Castle NA, Stevens EB (2015). A newly identified selective mechano-sensitive K2P opener reduces rat dorsal root ganglion (DRG) neurone excitability. Society for Neuroscience (USA) annual meeting, Chicago.
  • Mathie A, Veale EL (2014). Pharmacological and genetic recovery of current through truncated and mutated K2P channels. Acta Physiologica 211 (S697): 39P.
  • Hassan M, Walsh Y, Al-Moubarak E, Frimpong S, Golledge R, Kehoe B, Prestwich S, Rothou D, Sutcliffe D, Mathie A, Veale EL (2014). Inward Rectification of Birk Barel mutated human and mouse TASK3 potassium channels. Physiology 2014, PCB053.
  • Al Moubarak E, Veale, EL, Mathie A (2013). Regulation of TREK1 two pore domain potassium channels by amitriptyline. IUPS 2013 PCD131.
  • Al Moubarak E, Veale, EL, Mathie A (2013). Regulation of TREK1 two pore domain potassium channels by citalopram. FASEB J 27: 913.31.
  • Rees KA, Veale EL, Mathie A (2011). Modulation of surface expression of two pore domain potassium channels by N-linked glycosylation. NCMLS 5th New Frontiers Symposium: Ion channels in health and disease. P25.
  • Cao L, Veale EL, Mathie A, Stevens E (2010). Differential modulation of TREK-1, TASK-3 and TRESK K2P ion channels by BL-1249. Program No. 174.6/KK13. 2010 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience Online.
  • Rees KA, Veale EL, Mathie A (2010). Stimulation of heteromeric TASK channel trafficking by 14-3-3β protein. Basic and Clinical Pharmacology & Toxicology 107 (Suppl. 1), 119.

Full List of Refereed Conference Contributions

  • Veale EL, Aller MI, Mathie A (2008). Functional characteristics and regulation of mouse THIK1 two-pore-domain potassium channels. Beijing Joint Conference of Physiological Sciences 2008, Acta Physiol Sinica 60 S1: 229.
  • Clarke CE, Veale EL, Mathie A, Wyse, K, Torres A, Pages G, Kuchel PW, Vandenberg JI (2007). A link to two-pore domain potassium channel regulation.  AuPS Proceedings 38: 36P
  • Veale EL, Clarke CE, Mathie A (2007). Identification of a region of TASK3 two pore domain K channels critical for their modulation by methanandamide. Life Sci Conference (Glasgow): PC187.
  • Brickley SG, Aller MI, Veale EL, Sandu C, Alder FG, Sambi H, Mathie A, Wisden W (2007). Two-pore domain potassium channels enable sustained high-frequence firing. Brit Neurosci Assoc Abstr 19: P87.
  • Aller MI, Brickley SG, Mathie A, Sandu C, Veale EL, Wisden W (2006). Two-pore potassium channel expression enables sustained high-frequency firing. FENS Abstr 3: A189.1.
  • Veale EL, Sutton GL, Mathie A (2006). Inhibition of TASK3 two pore domain potassium channels following activation of protein kinase C. Proc Physiol Soc 3: PC28.
  • Evans LJ, Veale EL, Mathie A (2006). Differential inhibition of TASK K2P channels by copper. Acta Physiologica 186 (S1): 189P.
  • Brickley SG, Veale EL, Aller MI, Linden A-M, Sandu C, Schwaninger M, Evans L, Korpi E, Wisden, W, Mathie A (2005). Modifying the subunit composition of TASK channels alters the modulation of a leak conductance in adult cerebellar granule neurons. Program No. 609.11. 2005 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience Online.
  • Veale EL, Clarke CE, Mathie A (2005). A key glutamate residue (E30), conserved in many K channels, regulates the gating of TASK3 two pore domain potassium channels. J Physiol 567: PC196.
  • Kennard LE, Veale EL, Mathie A (2005). Muscarinic inhibition of TASK-3 two-pore domain potassium channels. Biophys J 88: 2281-Pos.
  • Veale EL, Clarke CE, Mathie A (2005). Block of TASK1 and TASK3 K2P channels by zinc: interactions with pHo and [K]o. J Physiol Biochem 61: 109-110.
  • Kennard LE, Veale EL, Mathie A (2004). Inhibition of the human two-pore domain potassium channel, TREK1, by fluoxetine and its metabolite norfluoxetine. FENS Abstr 2: A082.9.
  • Clarke CE, Green PJ, Veale EL, Meadows HJ, Mathie A (2003). The involvement of residues H98 and E70 in the block of the human two pore domain potassium channel, TASK-3, by zinc. J Physiol 547P: C46.
  • Mathie A, Veale EL (2003). Voltage-gated ion channels. ICNIRP/WHO International Workshop on ELF Weak Electric Field Effects on the Body (National Radiological Protection Board, Oxford): 7-8.
  • Mathie A, Clarke CE, Ranatunga KM, Veale EL (2003).Two-pore domain potassium channels in mammalian neurons. J Physiol 547P: SA7.
  • Mathie A, Clarke CE, Kennard LE, Ranatunga KM, Veale EL (2003). Two-pore domain potassium channels and their role in the regulation of neuronal excitability. 3rd Federation of European Physiological Societies meeting (Nice): S23-1.
  • Morris NP, Veale, E, Heintz N, Rudy B. & Robertson B (2003).Cerebellar Purkinje cell voltage-gated potassium currents are significantly reduced in Kv3.3 knockout mice. 16th Meeting of the British Neuroscience Association. 20.01.
  • Morris NP, Veale E, Chiu SY & Robertson B (2002). Effects of subunit selective dendrotoxins on spontaneous inhibitory postsynaptic currents in cerebellar Purkinje cells of Kv1.1 null mutant mice. J.Physiol. 544 73P.
  • Coombs ID, Veale EL & Robertson B (2001). External cations influence deactivation rates of the HCN-1 channel expressed in tSA cells. Biophys J. 82 578a.
  • Veale E, Morris N, Fyffe R & Robertson B (2001). Electrophysiological and molecular characteristics of the hyperpolarization-activated cation current in the medial septum/diagonal band complex in the mouse. 34th International Union of Physiological Sciences Congress (Christchurch) 699.
  • Whittle AJ, Coombs ID, Martin HGS, Veale EL & Robertson B (2000). Properties of the murine hyperpolarization-activated channel mHCN1 expressed in xenopus laevis oocytes. J.Physiol. 528 55-56P.

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Refereed Reviews

  • Warren G, McKown R, Teutonico R, Kuroki G, Veale E & Sagen K (1997). Arabidposis mutants impaired in freezing tolerance after cold acclimation. in Plant Cold Hardiness. pp 45-56, Springer, New York

 

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Last Updated 01/08/2019