Dr Jonathan Gale
Hair cells are the sensory receptors of the ear that enable us to hear and balance. The main focus of my lab is to determine the signalling events that control repair and regeneration of hair cells after cell damage or loss. The avian inner ear has a powerful ability to regenerate hair cells after injury whereas in mammals that regenerative potential is absent. We are taking a comparative approach. By studying the signalling processes in these two species we aim to discover the essential elements that control hair cell repair and regeneration.
A combination of dynamic imaging, cellular and molecular techniques are being used to study intracellular signalling in and between support cells. Why the support cells you may ask? These are the progenitor cells that divide or undergo phenotypic conversion to produce hair cells.A range of different techniques are used to damage hair cells. We measure spatio-temporal changes in a number of candidate signaling pathways and molecules e.g. intracellular calcium and cyclic AMP in response to hair cell damage or loss. Inhibitor and promotor molecules of different signalling pathways are used to investigate the mechanisms underlying hair cell regeneration. Other projects related include investigating the potential for hair cells to repair after damage, and the role of Rho proteins and of gap junction proteins in hair cell repair and regeneration. Some projects involve collaborative work with Dr Sally Dawson here at the UCL Ear Institute
Calcium signalling and mitochondrial function in cell physiology and pathophysiology.
Identifying Candidates for Hair Cell Protection
Intracellular and intercellular signalling mechanisms in health and disease
Sensory cell death in the inner ear, repair of the sensory epithelia and protection and regeneration of hair cells
I have taught on the Biomedical Sciences program since 2000 and now run the Anatomy and Physiology of the Audiovestibular System Modules for the BSc and MSc's at the the UCL Ear Institute.
Mr Hashim Ahmed; Dr David Werring; Prof Michael Duchen; Dr Emily Towers; Dr Dan Jagger; Prof Andrew Forge; Dr Sally Dawson; Prof Stephen Moss; Prof Mark Lythgoe; Dr Adam Badar; Dr Nicolas Daudet
- Marinari E, Mehonic A, Curran S, Gale J, Duke T, Baum B (2012). Live-cell delamination counterbalances epithelial growth to limit tissue overcrowding.. Nature, 484(7395), 542 - 545. doi:10.1038/nature10984
- Chrysostomou E, Gale JE, Daudet N (2012). Delta-like 1 and lateral inhibition during hair cell formation in the chicken inner ear: evidence against cis-inhibition.. Development, 139(20), 3764 - 3774. doi:10.1242/dev.074476
- Mao Y, Tournier AL, Gale JE, Bates PA, Tapon N, Thompson BJ (2011). Planar polarisation of the atypical myosin Dachs orients cell divisions in Drosophila. Genes & Dev, , - . doi:10.1101/gad.610511
- Towers ER, Kelly JJ, Sud R, Gale JE, Dawson SJ (2011). Caprin-1 is a target of the deafness gene Pou4f3 and is recruited to stress granules in cochlear hair cells in response to ototoxic damage. Journal of Cell Science, 124(7), 1145 - 1155.
- Housley G, Gale J (2010). Purinergic signalling in the inner ear-perspectives and progress. Purinergic Signalling, 6(2), 151 - 153.
- Gale JE, Burden M, Mann Z, Lahne M (2010). Aminoglycoside Induced Hair Cell Death in Neonatal Rat Cochlea Explants Is Dependent on the Extracellular Calcium Concentration.
- Goodyear RJ, Legan PK, Christiansen JR, Xia B, Korchagina J, Gale JE, Warchol ME, Corwin JT, Richardson GP (2010). Identification of the Hair Cell Soma-1 Antigen, HCS-1, as Otoferlin.. J Assoc Res Otolaryngol., 11(4), 573 - 586.
- Gale J, Jagger D (2010). Cochlear supporting cells. In Fuchs P (Ed.), The Ear (pp. 307 - 327). : Oxford Univ Pr.
- Lahne M, Gale JE (2010). Damage-induced cell-cell communication in different cochlear cell types via two distinct ATP-dependent Ca2+ waves. PURINERG SIGNAL, 6(2), 189 - 200. doi:10.1007/s11302-010-9193-8
- Bird JE, Daudet N, Warchol ME, Gale JE (2010). Supporting cells eliminate dying sensory hair cells to maintain epithelial integrity in the avian inner ear. Journal of Neuroscience, 30(37), 12545 - 12556.
- Chrysostomou E, Gale J, Daudet N (2009). Investigating the dynamics of Notch signalling in the embryonic chick inner ear using a reporter-based approach. doi:10.1016/j.mod.2009.06.594
- Mann Z, Jagger D, Duchen M, Gale J (2009). Neomycin Mediates Changes in Cytosolic and Mitochondrial Calcium in Rat Hair Cells in Vitro.
- Mann ZF, Duchen MR, Gale JE (2009). Mitochondria modulate the spatio-temporal properties of intra- and intercellular Ca2+ signals in cochlear supporting cells. Cell Calcium, 46(2), 136 - 146.
- Tornari C, Towers E, Gale J, Dawson S (2008). The Hair Cell Transcription Factor POU4F3 (Brn-3c) Is a Transcriptional Activator of the Orphan Steroid/thyroid Nuclear Receptor NR2F2.
- Gburcik V, Towers E, Gale J, Dawson S (2008). A Targeted Strategy for Identifying and Evaluating Molecular Candidates of Sensory Hair Cell Protection.
- Lahne M, Gale JE (2008). Damage-induced activation of ERK1/2 in cochlear supporting cells is a hair cell death-promoting signal that depends on extracellular ATP and calcium. Journal of Neuroscience, 28(19), 4918 - 4928.
- Goodyear RJ, Gale JE, Ranatunga KM, Kros CJ, Richardson GP (2008). Aminoglycoside-induced phosphatidylserine externalization in sensory hair cells is regionally restricted, rapid, and reversible. Journal of Neuroscience, 28(40), 9939 - 9952.
- Piazza V, Ciubotaru CD, Gale JE, Mammano F (2007). Purinergic signalling and intercellular Ca2+ wave propagation in the organ of Corti. Cell Calcium, 41(1), 77 - 86.
- Drew LJ, Rugiero F, Cesare P, Gale JE, Abrahamsen B, Bowden S, Heinzmann S, Robinson M, Brust A, Colless B, Lewis RJ, Wood JN (2007). High-Threshold Mechanosensitive Ion Channels Blocked by a Novel Conopeptide Mediate Pressure-Evoked Pain. PLoS ONE, 2(6), - .
- Lahne M, Gale J (2007). Inhibiting Neomycin-Induced ERK Activation Delays IHC Death in Neonatal Rat Cochlear Cultures.
- Tritsch NX, Yi E, Gale JE, Glowatzki E, Bergles DE (2007). The origin of spontaneous activity in the developing auditory system. Nature, 450(7166), 50 - 55.
- Ricci AJ, Kachar B, Gale J, Van Netten SM (2006). Mechano-electrical transduction: New insights into old ideas. Journal of Membrane Biology, 209(2-3), 71 - 88.
- Bird J, Warchol M, Gale J (2006). Mitogen-Activated Protein Kinases Regulate Both Wound Closure and Damage-Induced Proliferation in Epithelial Cultures of Mature Avian Utricle.
- Mann Z, Duchen M, Gale J (2006). Mitochondria Regulate Agonist Induced Cytoplasmic Calcium Signals in Cochlear Support Cells.
- Lahne M, Gale J (2005). Gap Junction Involvement in Damage-Induced ERK1/2 Activation in Neonatal Mammalian Cochlear Cultures.
- Gale JE, Ciubotaru CD, Piazza V, Mammano F (2004). Sensing noise damage in the inner ear through intercellular calcium waves.
- Ashmore J, Gale J (2004). The cochlear amplifier.. Current biology : CB, 14(11), R403 - 404.
- Matsui JI, Gale JE, Warchol ME (2004). Critical signaling events during the aminoglycoside-induced death of sensory hair cells in vitro. Journal of Neurobiology, 61(2), 250 - 266.
- Gale JE, Piazza V, Ciubotaru CD, Mammano F (2004). A mechanism for sensing noise damage in the inner ear. Current Biology, 14(6), 526 - 529.
- Bird J, Wong Y, Gale J (2003). Laser Lesioning of Chick Vestibular Epithelial Cultures Triggers Localised MAPK Phosphorylation and Proliferative Activity.
- Ako EO, Gale JE (2003). UTP and ATP evoke increases in intracellular Ca2+ via P2Y receptors in cultured chick utricular epithelia.
- Gale J, Ako E (2003). ATP Acts as an Intercellular Signalling Molecule After Laser Lesioning of Cultured Chick Utricular Epithelia.
- Bird JE, Gale JE (2003). Spatio-temporal aspects of damage-induced proliferation in chick vestibular epithelial cultures.
- Gale JE, Meyers JR, Periasamy A, Corwin JT (2002). Survival of bundleless hair cells and subsequent bundle replacement in the bullfrog's saccule. Journal of Neurobiology, 50(2), 81 - 92.
- Piazza V, Ciubotaru CD, Gale JE, Mammano F (2002). Oscillatory behaviour of intracellular Ca2+ in supporting cells of the organ of Corti.
- Gale JE, Marcotti W, Kennedy HJ, Kros CJ, Richardson GP (2001). FM1-43 dye behaves as a permeant blocker of the hair-cell mechanotransducer channel. Journal of Neuroscience, 21(18), 7013 - 7025.
- Gale JE, Warchol ME (2001). Rapid intercellular calcium signalling and actin cable formation at wound sites after laser lesioning in chick vestibular epithelial cultures.
- Gale JE, Faucheux F, Kennedy HJ, Richardson GP (2000). FM1-43 loading of mouse cochlear hair cells in vitro is rapid, blocked by pretreating cultures with EGTA and recovers from Ca2+-chelation over 24 hours.
- Gale JE, Meyers JR, Corwin JT (2000). Solitary hair cells are distributed throughout the extramacular epithelium in the bullfrog's saccule. JARO - Journal of the Association for Research in Otolaryngology, 1(2), 172 - 182.
- Ashmore J, Gale J (2000). The cochlea. Current Biology, 10(9), - .
- Gale JE, Ashmore JF (1997). An intrinsic frequency limit to the cochlear amplifier. Nature, 389(6646), 63 - 66.
- Gale JE, Ashmore JF (1997). The outer hair cell motor in membrane patches. European Journal of Physiology, 434, 267 - .
- Ashmore JF, Gale JE (1997). The intrinsic limit for active cochlear mechanics. In Lewis ER, Long GR, Lyon RF, Narins PM, Steele CR, Hecht-Poinar E (Ed.), Diversity in Auditory Mechanics (pp. 481 - 486). : .
- Tunstall MJ, Gale JE, Ashmore JF (1995). Action of salicylate on membrane capacitance of outer hair cells from the guinea-pig cochlea. Journal of Physiology, 485(3), 739 - 752.
- Ashmore JF, Mammano F, Gale JE, Tunstall MJ (1995). The pharmacology of the outer hair cell motor. In Flock A, Ottoson D, Ulfendahl M (Ed.), Active Hearing (pp. 337 - 348). : .
- Gale JE, Ashmore JF (1994). Charge displacement induced by rapid stretch in the basolateral membrane of the guinea-pig outer hair cell.. Proc Biol Sci., 255, 243 - 249.
- Gburcik V, Towers E, Gale JE, Dawson S (). XXXX (subject to patent application) is a target of the hair cell transcription factor Barhl1 and its expression is induced in response to ototoxic damage.. J. Biol. Chem, , - .
- Mann ZF, Ushakov K, Jagger DJ, Duchen MJ, Gale JE (). Aminoglycosides mediate physiological and pathological changes in hair cell cytosolic and mitochondrial calcium.. , , - .