Dr Ewan Smith


University position

Reader

Dr Ewan Smith is pleased to consider applications from prospective PhD students.

Departments

Department of Pharmacology

Home page

http://www.phar.cam.ac.uk/researc...

Research Themes

Cellular and Molecular Neuroscience

Clinical and Veterinary Neuroscience

Interests

The main interest of the Smith lab is to understand the molecular mechanisms by which sensory neurones detect noxious stimuli, so-called nociceptors. We are particularly interested in how acid activates nociceptors in both physiological and pathophysiological states.

A further area of interest in the Smith lab is the unusual physiology of the naked mole-rat, an animal that is cold-blooded, lives for 30+ years, is resistant to cancer and is also eusocial! We aim to conduct comparative physiology and genetics with the naked mole-rat in order to identify molecules and circuits that underlie aspects of their “odd” physiology, results from such work will lead to a greater understanding of how “normal” physiology works in other mammals including humans.

Research Focus

Keywords

nociception

ion channels

acid

arthritis

inflammation

Clinical conditions

Cancers

Genetic disorders

Neurodegeneration

Pain

Equipment

Behavioural analysis

Calcium imaging

Cell culture

Confocal microscopy

Electrophysiological recording techniques

Fluorescence microscopy

Immunohistochemistry

Whole cell patch clamp

Collaborators

Cambridge

David Bulmer

Frances Henson

Tony Jackson

Deepak Jadon

Walid Khaled

Michael Lee

Taufiq Rahman

Mathew Van de Pette

Geoff Woods

United Kingdom

Franziska Denk Web: https://www.franziskadenk.com/iqp7p6x...

Daniel Frankel Web: http://www.ncl.ac.uk/ceam/st...

Kenny Rankin Web: http://www.ncl.ac.uk/medical...

International

Ishmail Abdus-Saboor Web: https://www.abdus-saboorlab.com/new-page-2

Victoria Abraira Web: https://www.abrairalab.org/

Nicolas Cenac Web: https://www.irsd.fr/nicolas...

Paul Heppenstall Web: http://phdneurobiology.sissa.it/eng/fac...

Associated News Items


Publications

2020

Browe BM, Olsen AR, Ramirez C, Rickman RH, Smith ES and Park TJ (2020), “The naked mole-rat has a functional purinergic pain pathway despite having a non-functional peptidergic pain pathway.” Neurobiology of Pain 100051

Callejo G, Pattison LA, Greenhalgh JC, Chakrabarti S, Andreopoulou E, Hockley JRF, Smith ES and Rahman T (2020), “In silico screening of GMQ-like compounds reveals guanabenz and sephin1 as new allosteric modulators of acid-sensing ion channel 3. ” Biochemical Pharmacology 174: 113834

Chakrabarti S, Hore Z, Pattison LA, Lalnunhlimi S, Bhebhe CN, Callejo G, Bulmer DC, Taams LS Denk F and Smith ES (2020), “Sensitization of knee-innervating sensory neurons by tumor necrosis factor-α activated fibroblast-like synoviocytes: an in vitro, co-culture model of inflammatory pain.” Pain 161: 2129-2141

Chakrabarti S, Jadon D, Bulmer DC and Smith ES (2020), “Human osteoarthritic synovial fluid increases excitability of mouse dorsal root ganglion sensory neurons: an in-vitro translational model to study arthritic pain” Rheumatology 59: 62-67

Chakrabarti S, Pattison LA, Doleschall B, Rickman RH, Callejo G, Heppenstall PA and Smith ES (2020), “Intra-articular AAV-PHP.S mediated chemogenetic targeting of knee-innervating DRG neurons alleviates inflammatory pain in mice.” Arthritis and Rheurmatology

Du Z, Chakrabarti S, Kulaberoglu Y, Smith ES, Dobson CM, Itzhaki L and Kumita J (2020), “Probing the unfolded protein response in long-lived naked mole-rats. ” Biochem Biophys Res Comm 529: 1151-1157

Hadi F, Kulaberoglu Y, Lazarus K, Bach K, Ugur R, Beattie P, Smith ES and Khaled WT (2020), “Transformation of naked mole-rat cells” Nature 583: E1-E7

Lee M, Nahorski M, Hockley JRF, Lu V, Ison G, Pattison LA, Callejo G, Stouffer K, Fletcher E, Drissi I, Wheeler D, Ernfors P, Menon D, Reimann F, Smith ES and Woods CG (2020), “Human labour pain is influenced by the voltage-gated potassium channel KV6.4 subunit. ” Cell Reports 32: 107941

Smith ES, Park TJ and Lewin GR (2020), “Independent evolution of pain insensitivity in African mole-rats: origins and mechanisms.” Journal of Comparative Physiology A 313-325

Taylor TS, Konda P, John SS, Bulmer DC, Hockley JRF and Smith ES (2020), “Galanin suppresses visceral afferent responses to noxious mechanical and inflammatory stimuli. ” Physiological Reports 8: e14326

2019

Hockley JRF, Taylor TS, Callejo G, Wilbrey AL, Gutterridge A, Bach K, Winchester WJ, Bulmer DC, McMurray G, and Smith ES (2019), “Single-cell RNAseq reveals seven classes of colonic sensory neuron. ” Gut 68: 633-644

Kulaberoglu Y, Bhushan B, Hadi F, Chakrabarti S, Khaled WT, Rankin K, Smith ES and Frankel D (2019), “The material properties of naked mole-rat hyaluronan” Scientific Reports 9: 6632

Pattison, LA, Callejo G and Smith ES (2019), “Evolution of acid nociception: ion channels and receptors for detecting acid” Phil Trans Roc Soc B 374: 20190291

2018

Bautzova T, Hockley JR, Perez-Berezo T, Pujo J, Tranter MM, Desormeaux C, Barbaro MR, Basso L, Le Faouder P, Rolland C, Malapert P, Moqrich A, Eutamene H, Denadi-Souza A, Vergnolle N, Smith ES, Hughes DI, Barabara G, Dietrich G, Bulmer DC and Cenac N (2018), “5-oxoETE triggers nociception in constipation predominant irritable bowel syndrome through MAS-related G protein coupled receptor D” Science Signalling 11: eaal2171

Chakrabarti S, Pattison LA, Singhal K, Hockley JRF, Callejo G and Smith ES (2018), “Acute inflammation sensitizes knee-innervating sensory neurons and decreases mouse digging behavior in a TRPV1-dependent manner. ” Neuropharmacology 143: 49-62

Hockley, JRF, Smith, ES and Bulmer, DC (2018), “Human visceral nociception: findings from translational studies in human tissue. ” Am J Physiol Gastro Liv Physiol G464-G472

Husson Z and Smith ES (2018), “Naked mole-rat cortical neurons are resistant to acid-induced cell death. ” Molecular Brain 11: 26

Schuhmacher, LN, Callejo, G, Srivats, S and Smith, ES (2018), “Naked mole-rat acid-sensing ion channel 3 forms nonfunctional homomers, but functional heteromers. ” J Biol Chem 293: 1756-66

Wright AJ, Husson ZM, Hu DE, Callejo G, Brindle KM and Smith E S (2018), “Increased hyperpolarized [1-13C]lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized 13C-labeled bicarbonate. ” NMR Biomedicine e3892

2017

Park TJ, Reznick J, Peterson BL, Blass G, Omerbašić D, Bennett NC, Kuich PHJL, Zasada C, Browe BM, Hamann W, Applegate DT, Radke MH, Kosten T, Lutermann H, Gavaghan V, Eigenbrod O, Bégay V, Amoroso VG, Govind V, Minshall RD, Smith ESJ, Larson J, Gotthardt M, Kempa S, and Lewin GR (2017), “Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat.” Science 356: 307-311

Peiris M, Hockley JR, Reed DE, Smith ESJ, Bulmer DC, Blackshaw LA. (2017), “Peripheral KV7 channels regulate visceral sensory function in mouse and human colon.” Molecular Pain 13:1744806917709371

Prato V, Taberner FJ, Hockley JRF, Callejo G, Arcourt A, Tazir B, Hammer L, Schad P, Heppenstall PA, Smith ES and Lechner, S.G. (2017), “Functional and molecular characterization of mechanoinsensitive "silent" nociceptors.” Cell Reports 21: 3102-3115

Wetzel C, Pifferi S, Picci C, Gök C, Hoffmann D, Bali KK, Lampe A, Lapatsina L, Fleischer R, Smith ES, Bégay V, Moroni M, Estebanez L, Kühnemund J, Walcher J, Specker E, Neuenschwander M, von Kries JP, Haucke V, Kuner R, Poulet JF, Schmoranzer J, Poole K, Lewin GR. (2017), “Small-molecule inhibition of STOML3 oligomerization reverses pathological mechanical hypersensitivity.” Nature Neuroscience 20:209-218

2016

da Silva Serra I, Husson Z, Bartlett JD, Smith ES (2016), “Characterization of cutaneous and articular sensory neurons” Molecular Pain 12: 1-14

Mason MJ, Cornwall HL and Smith ES (2016), “Ear Structures of the Naked Mole-Rat, Heterocephalus glaber, and Its Relatives (Rodentia: Bathyergidae)” PLoS One 11: e0167079

Omerbašić D, Smith ES, Moroni M, Homfeld J, Eigenbrod O, Bennett NC, Reznick J, Faulkes CG, Selbach M, Lewin GR. (2016), “Hypofunctional TrkA Accounts for the Absence of Pain Sensitization in the African Naked Mole-Rat.” Cell Reports 17: 748-758

Schuhmacher LN and Smith ES (2016), “Expression of acid-sensing ion channels and selection of reference genes in mouse and naked mole rat” Molecular Brain 9: 97

2015

Jeggle P, Smith ES, Stewart AP, Haerteis S, Korbmacher C, Edwardson JM (2015), “Atomic force microscopy imaging reveals the formation of ASIC/ENaC cross-clade ion channels.” Biochem Biophys Res Commun 464(1):38-44 Details

Omerbašić D, Schuhmacher LN, Bernal Sierra YA, Smith ES, Lewin GR (2015), “ASICs and mammalian mechanoreceptor function.” Neuropharmacology 94:80-86 Details

Schuhmacher LN, Srivats S, Smith ES (2015), “Structural domains underlying the activation of Acid-sensing ion channel 2a.” Mol Pharmacol 87(4):561-71 Details

Schuhmacher, L. N., Husson, Z. and Smith, E. S (2015), “The naked mole-rat as an animal model in biomedical research: current perspectives. ” Open Access Animal Physiology 137-148

2014

Kozlenkov A, Lapatsina L, Lewin GR, Smith ES (2014), “Subunit-specific inhibition of acid sensing ion channels by stomatin-like protein 1.” J Physiol 592(Pt 4):557-69 Details

Lewin GR, Lechner SG, Smith ES (2014), “Nerve growth factor and nociception: from experimental embryology to new analgesic therapy.” Handb Exp Pharmacol 220:251-82 Details

Rahman T, Smith ES (2014), “In silico assessment of interaction of sea anemone toxin APETx2 and acid sensing ion channel 3.” Biochem Biophys Res Commun 450(1):384-9 Details

2013

Smith ES, Martinez-Velazquez L, Ringstad N (2013), “A chemoreceptor that detects molecular carbon dioxide.” J Biol Chem 288(52):37071-81 Details

2012

Brand J, Smith ES, Schwefel D, Lapatsina L, Poole K, Omerbašić D, Kozlenkov A, Behlke J, Lewin GR, Daumke O (2012), “A stomatin dimer modulates the activity of acid-sensing ion channels.” EMBO J 31(17):3635-46 Details

Lapatsina L, Jira JA, Smith ES, Poole K, Kozlenkov A, Bilbao D, Lewin GR, Heppenstall PA (2012), “Regulation of ASIC channels by a stomatin/STOML3 complex located in a mobile vesicle pool in sensory neurons.” Open Biol 2(6):120096 Details

St John Smith E, Purfürst B, Grigoryan T, Park TJ, Bennett NC, Lewin GR (2012), “Specific paucity of unmyelinated C-fibers in cutaneous peripheral nerves of the African naked-mole rat: comparative analysis using six species of Bathyergidae.” J Comp Neurol 520(12):2785-803 Details

Stock K, Kumar J, Synowitz M, Petrosino S, Imperatore R, Smith ES, Wend P, Purfürst B, Nuber UA, Gurok U, Matyash V, Wälzlein JH, Chirasani SR, Dittmar G, Cravatt BF, Momma S, Lewin GR, Ligresti A, De Petrocellis L, Cristino L, Di Marzo V, Kettenmann H, Glass R (2012), “Neural precursor cells induce cell death of high-grade astrocytomas through stimulation of TRPV1.” Nat Med Details

2011

Lechner SG, Markworth S, Poole K, Smith ES, Lapatsina L, Frahm S, May M, Pischke S, Suzuki M, Ibañez-Tallon I, Luft FC, Jordan J, Lewin GR (2011), “The molecular and cellular identity of peripheral osmoreceptors.” Neuron 69(2):332-44 Details

Smith ES, Omerbašić D, Lechner SG, Anirudhan G, Lapatsina L, Lewin GR (2011), “The molecular basis of acid insensitivity in the African naked mole-rat.” Science 334(6062):1557-60 Details

2010

Brand A, Smith ES, Lewin GR, Park TJ (2010), “Functional neurokinin and NMDA receptor activity in an animal naturally lacking substance P: the naked mole-rat.” PLoS One 5(12):e15162 Details

Smith ES, Blass GR, Lewin GR, Park TJ (2010), “Absence of histamine-induced itch in the African naked mole-rat and "rescue" by Substance P.” Mol Pain 6:29 Details

Stürzebecher AS, Hu J, Smith ES, Frahm S, Santos-Torres J, Kampfrath B, Auer S, Lewin GR, Ibañez-Tallon I (2010), “An in vivo tethered toxin approach for the cell-autonomous inactivation of voltage-gated sodium channel currents in nociceptors.” J Physiol 588(Pt 10):1695-707 Details

2009

Smith ES, Lewin GR (2009), “Nociceptors: a phylogenetic view.” J Comp Physiol A Neuroethol Sens Neural Behav Physiol 195(12):1089-106 Details

2008

Park TJ, Lu Y, Jüttner R, Smith ES, Hu J, Brand A, Wetzel C, Milenkovic N, Erdmann B, Heppenstall PA, Laurito CE, Wilson SP, Lewin GR (2008), “Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber).” PLoS Biol 6(1):e13 Details

Smith ES, Momin A (2008), “Persistent pain: the contribution of Na(V)1.9.” J Physiol 586(9):2249-50 Details

2007

Cadiou H, Studer M, Jones NG, Smith ES, Ballard A, McMahon SB, McNaughton PA (2007), “Modulation of acid-sensing ion channel activity by nitric oxide.” J Neurosci 27(48):13251-60 Details

Smith ES, Cadiou H, McNaughton PA (2007), “Arachidonic acid potentiates acid-sensing ion channels in rat sensory neurons by a direct action.” Neuroscience 145(2):686-98 Details

Smith ES, Zhang X, Cadiou H, McNaughton PA (2007), “Proton binding sites involved in the activation of acid-sensing ion channel ASIC2a.” Neurosci Lett 426(1):12-7 Details