Dr Ewan Smith University positionReader Dr Ewan Smith is pleased to consider applications from prospective PhD students. DepartmentsHome pagehttp://www.phar.cam.ac.uk/researc... Research ThemesInterestsThe 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
EquipmentBehavioural analysis Calcium imaging Cell culture Confocal microscopy Electrophysiological recording techniques Fluorescence microscopy Immunohistochemistry Whole cell patch clamp Collaborators
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Publications2022Buffenstein R, Amoroso V, Andziak B, Avdieiev S, Azpurua J, Barker AJ, Bennett NC, Brieño-Enríquez MA, Bronner GN, Coen C, Delaney MA, Dengler-Crish CM, Edrey YH, Faulkes CG, Frankel D, Friedlander G, Gibney PA, Gorbunova V, Hine C, Holmes MM, Jarvis JUM, Kawamura Y, Kutsukake N, Kenyon C, Khaled WT, Kikusui T, Kissil J, Lagestee S, Larson J, Lauer A, Lavrenchenko LA, Lee A, Levitt JB, Lewin GR, Lewis Hardell KN, Lin TD, Mason MJ, McCloskey D, McMahon M, Miura K, Mogi K, Narayan V, O'Connor TP, Okanoya K, O'Riain MJ, Park TJ, Place NJ, Podshivalova K, Pamenter ME, Pyott SJ, Reznick J, Ruby JG, Salmon AB, Santos-Sacchi J, Sarko DK, Seluanov A, Shepard A, Smith M, Storey KB, Tian X, Vice EN, Viltard M, Watarai A, Wywial E, Yamakawa M, Zemlemerova ED, Zions M and Smith ESJ (2022), “The naked truth: a comprehensive clarification and classification of current ‘myths’ in naked mole-rat biology” Biological Reviews 97: 115-140 Cagan A, Baez-Ortega A, Brzozowska N, Abascal F, Coorens THH, Sanders MA, Lawson ARJ, Harvey LMR, Bhosle S, Jones D, Alcantara RE, Butler TM, Hooks Y, Roberts K, Anderson E, Lunn S, Flach E, Spiro S, Januszczak I, Wrigglesworth E, Jenkins H, Dallas T, Masters N, Perkins MW, Deaville R, Druce M, Bogeska R, Milsom MD, Neumann B, Gorman F, Constantino-Casas F, Peachey L, Bochynska D, Smith ESJ, Gerstung M, Campbell PJ, Murchison EP, Stratton MR and Martincorena I (2022), “Somatic mutation rates scale with lifespan across mammals” Nature 604: 517-24 Latragna A, Sabaté San José A, Tsimpos P, Vermeiren S, Gualdani R, Chakrabarti S, Callejo G, Desiderio S, Shomroni O, Sitte M, Kricha S, Luypaert M, Vanhollebeke B, Laumet G, Salinas G, Smith ESJ, Ris L and Bellefroid EJ. (2022), “Prdm12 modulates pain-related behavior by remodeling gene expression in mature nociceptors” Pain 163: 927-941 2021Chakrabarti S, Ai M, Wong WYK, Newell K, Henson FMD and Smith ES (2021), “Functional characterization of ovine dorsal root ganglion neurons reveals peripheral sensitization after osteochondral defect. ” eNeuro ENEURO.0237-21.2021 Dulai JS, Smith ES and Rahman T (2021), “Acid-sensing ion channel 3: An analgesic target” Channels 15: 94-127 Pattison LA, Krock E, Svensson CI and Smith, ES (2021), “Cell–cell interactions in joint pain: rheumatoid arthritis and osteoarthritis” Pain 162: 714-717 Tan SL, Barri M, Atakpa-Adaji P, Taylor CW, Smith ES, and Murrell-Lagnado RD (2021), “P2X4 receptors mediate Ca2+ release from lysosomes in response to stimulation of P2X7 and H1 histamine receptors” Int J Mol Sci 22: 10492 2020Browe 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-? 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 2019Hockley 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 2018Bautzova 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 2017Park TJ, Reznick J, Peterson BL, Blass G, Omerbaši? 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 2016da 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 Omerbaši? 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 2015Jeggle 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 Omerbaši? 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 2014Kozlenkov 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 2013Smith ES, Martinez-Velazquez L, Ringstad N (2013), “A chemoreceptor that detects molecular carbon dioxide.” J Biol Chem 288(52):37071-81 Details 2012Brand J, Smith ES, Schwefel D, Lapatsina L, Poole K, Omerbaši? 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 2011Lechner 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, Omerbaši? 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 2010Brand 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 2009Smith ES, Lewin GR (2009), “Nociceptors: a phylogenetic view.” J Comp Physiol A Neuroethol Sens Neural Behav Physiol 195(12):1089-106 Details 2008Park 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 2007Cadiou 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 |