Biography
I am an award winning electron microscopist with over thirty years of experience in the principles and practical application of EM in both commercial and research sectors. My interest in microscopy began early with a birthday present of a small light microscope at 12.
Recognising its limitations, I saved up and acquired a more elaborate microscope. These microscopes established an interested in Protozoa, in particular, and so began my career in microscopy. This developed into the desire to be a researcher who used electron microscopes to study cells generally. I completed an undergraduate zoology degree at Manchester University which included Cell Biology and Protozoology courses, and did a third year project on the ultrastructure of rumen Protozoa. I obtained a First Class Honours and won the Zoology prize which was followed by a departmental PhD position to continue my study of rumen ciliates, presenting my work first at a meeting of the Royal Microscopical Society, at which I won a prize for the best young microscopist, and subsequently giving talks at UK protozoology conferences. Also during my PhD I made an early foray into immunofluorescence techniques, then in their infancy, X-ray microanalysis, and high resolution scanning electron microscopy (SEM) on a Phillips 400T TEM which was capable of in-lens imaging. This was the first high resolution imaging of protozoa certainly at Manchester and possibly elsewhere. I wrote three papers on my PhD research before submitting the final thesis and attending an international Protozoology conference in Nairobi.
Immediately after completing my PhD, I took up a post-doctoral position at Keele University, building on my EM and immunofluorescence experience, to study cytoskeletal structures after damaging the ear with strong antibiotics. This introduced me to hearing research, which I have been involved with ever since. At the end of my post-doctoral period I applied for and was awarded a Wellcome Trust lectureship (five years, with a two year extension) and with my start-up funds purchase an X-ray microanalysis system to add to Keele’s growing electron microscope unit. Our research into antibiotic damage and cytoskeletal organisation in the hearing organ continued, with a PhD student whom I co-supervised and we developed immunofluorescence microscopy at Keele and 3D reconstruction techniques to evaluate microtubular organisation in sensory cells of the inner ear. In 1994 I was given a permanent position at Keele University. I have been director of the Electron Microscope Unit (EMU) at Keele since 1995.
About that time, I led on the development of a new Neuroscience Principal Course at Keele, part of the dual honours system, and this has flourished, now boasting an intake of around 60 students p.a. I was course director for Neuroscience until my promotion to Reader in 2001, when I passed on the mantle, but I still organise several modules and teach on many more, having been nominated for student led teaching awards several times.
I was also at that time Director of the MacKay institute for Communication and Neuroscience, leading on research into hearing with grants from the MRC, Wellcome Trust and a number of hearing charities. After changes at Keele in 2006, I became theme lead for Cell and Tissue Engineering, subsequently splitting into a new theme which I led, Neuroscience and Human Metabolism, in the new Institute for Science and Technology in Medicine. Most recently I was promoted to a personal Chair in Cellular Neuroscience and became Research Director for the School of Life Sciences in 2015.
I am passing that mantle on as well in September 2020. I remain a leading researcher in hearing and hearing loss therapies, having held grants from the MRC, Wellcome Trust, BBSRC and a number of hearing charities. I am also responsible for Keele University’s Research Excellence Framework submission for Biological Sciences.
Research and scholarship
My main research interests lie in the field of auditory neuroscience. I am presently investigating the role of fibrocytes in the cochlea. These are cells that are associated with homeostatic mechanisms that regulate the composition of cochlear fluids. These cells appear to go wrong in certain forms of deafness, including age-related deafness (presbyacusis). My group has funding from Deafness Research UK to investigate whether a stem cell/replacement cell strategy might be employed to prevent or ameliorate age-related deafness by replacing defective fibrocytes.
The main techniques we employ are electron microscope, post-embedding immunogold electron microscopy, confocal microscopy and cell culturing. We have received funding for our work from the Wellcome Trust, MRC, Deafness Research UK, Midlands Institute of Otology, Royal Society, Physiological Society, British Tinnitus Association and others.
Another of my major research interests is cochlear hair cell structure, composition and function. I am focussing on the hair bundle and how the hairs (stereocilia - see picture) function to convert mechanical action from sound stimulation into electrical signals and nerve impulses in nerve fibres going to the brain.
I am also director of the Keele University Electron Microscope Unit which offers a range of microscopy facilities.
For some examples of our electron microscopy please visit the galleries on the EM Unit web pages:
Selected Publications
- 2020.
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Forgotten Fibrocytes: A Neglected, Supporting Cell Type of the Cochlea With the Potential to be an Alternative Therapeutic Target in Hearing Loss. Front Cell Neurosci, 532, vol. 13. link> doi> full text>2019.
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A Tmc1 mutation reduces calcium permeability and expression of mechanoelectrical transduction channels in cochlear hair cells. Proc Natl Acad Sci U S A, 20743-20749, vol. 116(41). link> doi> full text>2019.
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Ultrastructural localization of the likely mechanoelectrical transduction channel protein, transmembrane-like channel 1 (TMC1) during development of cochlear hair cells. Sci Rep, 1274, vol. 9(1). link> doi> full text>2019.
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The microRNA-183/96/182 Cluster is Essential for Stereociliary Bundle Formation and Function of Cochlear Sensory Hair Cells. Sci Rep, 18022, vol. 8(1). link> doi> full text>2018.
Full Publications Listshow
Journal Articles
- 2020.
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Forgotten Fibrocytes: A Neglected, Supporting Cell Type of the Cochlea With the Potential to be an Alternative Therapeutic Target in Hearing Loss. Front Cell Neurosci, 532, vol. 13. link> doi> full text>2019.
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A Tmc1 mutation reduces calcium permeability and expression of mechanoelectrical transduction channels in cochlear hair cells. Proc Natl Acad Sci U S A, 20743-20749, vol. 116(41). link> doi> full text>2019.
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Ultrastructural localization of the likely mechanoelectrical transduction channel protein, transmembrane-like channel 1 (TMC1) during development of cochlear hair cells. Sci Rep, 1274, vol. 9(1). link> doi> full text>2019.
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The microRNA-183/96/182 Cluster is Essential for Stereociliary Bundle Formation and Function of Cochlear Sensory Hair Cells. Sci Rep, 18022, vol. 8(1). link> doi> full text>2018.
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Mechanotransduction is required for establishing and maintaining mature inner hair cells and regulating efferent innervation. NATURE COMMUNICATIONS, Article ARTN 4015, vol. 9. link> doi> full text>2018.
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Mechanotransduction is required for establishing and maintaining mature inner hair cells and regulating efferent innervation. Nature Communications, Article 4015, vol. 9(1). link> doi> link> full text>2018.
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Spatiotemporal changes in the distribution of LHFPL5 in mice cochlear hair bundles during development and in the absence of PCDH15. PLoS ONE. doi>2017.
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Modeling and Preventing Progressive Hearing Loss in Usher Syndrome III. Sci Rep, 13480, vol. 7(1). link> doi> full text>2017.
- 2017.
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Strategies for immunohistochemical protein localization using antibodies: What did we learn from neurotransmitter transporters in glial cells and neurons. Glia, 2045-2064, vol. 64(12). link> doi> full text>2016.
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Neuronal vs glial glutamate uptake: Resolving the conundrum. Neurochem Int, 29-45, vol. 98. link> doi> full text>2016.
- 2016.
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Local mechanisms for loud sound-enhanced aminoglycoside entry into outer hair cells. Frontiers in cellular neuroscience, 130, vol. 9. doi> full text>2015.
- 2015.
- 2015.
- 2014.
- 2014.
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The role of transmembrane channel-like proteins in the operation of hair cell mechanotransducer channels. J Gen Physiol, 493-505, vol. 142(5). link> doi> full text>2013.
- 2013.
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Differences in magnetic particle uptake by CNS neuroglial subclasses: implications for neural tissue engineering. Nanomedicine (Lond), 951-968, vol. 8(6). link> doi> full text>2013.
- 2013.
- 2013.
- 2013.
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Marshalin, a microtubule minus-end binding protein, regulates cytoskeletal structure in the organ of Corti. Biol Open, 1192-1202, vol. 2(11). link> doi> full text>2013.
- 2012.
- 2012.
- 2012.
- 2011.
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QUANTIFICATION AND LOCALIZATION OF THE EAAC1 GLUTAMATE TRANSPORTER IN BRAIN. GLIA, S66, vol. 59. link>2011.
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Eps8 regulates hair bundle length and functional maturation of mammalian auditory hair cells. PLoS Biol, e1001048, vol. 9(4). link> doi> full text>2011.
- 2011.
- 2011.
- 2011.
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Mutations in protocadherin 15 and cadherin 23 affect tip links and mechanotransduction in mammalian sensory hair cells. PLoS One, e19183, vol. 6(4). link> doi> full text>2011.
- 2011.
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Abstracts of the british society of audiology short papers meeting on experimental studies of hearing and deafness. Int J Audiol, 672-722, vol. 49(9). doi>2010.
- 2010.
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Rapid, learning-induced inhibitory synaptogenesis in murine barrel field. J Neurosci, 1176-1184, vol. 30(3). link> doi> full text>2010.
- 2010.
- 2009.
- 2009.
- 2008.
- 2008.
- 2008.
- 2007.
- 2005.
- 2005.
- 2005.
- 2003.
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Synaptic distribution of glutamate transporters. Journal of Neurochemistry (Suppl)..2004.
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Distribution of the Glutamate/Aspartate Transporter GLAST in Relation to the Afferent Synapses of Outer Hair Cells in the Guinea Pig Cochlea. Journal of the Association for research in Otolaryngology, 234-247, vol. 3(3). doi>2002.
- 2002.
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An immunogold investigation of the distribution of calmodulin in the apex of cochlear hair cells. Hearing Research, 10-20, vol. 173(1-2). doi>2002.
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Roles of glutamate transporters in the brain. JOURNAL OF NEUROCHEMISTRY, 115, vol. 78. link>2001.
- 2000.
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Distribution of tropomyosin in guinea-pig cochlear hair cells. JOURNAL OF PHYSIOLOGY-LONDON, 92P-93P, vol. 527. link>2000.
- 2000.
- 1999.
- 1998.
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Supporting cell processes at the base of cochlear inner hair cells label for the glutamate/aspartate transporter (GLAST). EUROPEAN JOURNAL OF NEUROSCIENCE, 285, vol. 10. link>1998.
- 1998.
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The effects of lowering extracellular [Ca2+] on the structure of the stereociliary bundle of turtle cochlear hair cells. JOURNAL OF PHYSIOLOGY-LONDON, P131, vol. 504P. link>1997.
- 1997.
- 1997.
- 1996.
- 1996.
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A COMPARISON OF THE IMMUNOLABELING PATTERNS WITH ANTIBODIES TO KERATAN SULFATE AND ELASTIN IN GUINEA-PIG COCHLEA HAIR BUNDLES. JOURNAL OF PHYSIOLOGY-LONDON, P32-P33, vol. 485P. link>1995.
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FIELD-EMISSION SCANNING ELECTRON-MICROSCOPY OF COCHLEAR HAIR-CELLS - TIP LINKS, LATERAL LINKS AND TIP JUNCTIONS ON STEREOCILIA. JOURNAL OF PHYSIOLOGY-LONDON, P2, vol. 485P. link>1995.
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MECHANOTRANSDUCTION CHANNELS ON COCHLEAR HAIR-CELLS COULD BE OPERATED BY SHEAR DISPLACEMENT. JOURNAL OF PHYSIOLOGY-LONDON, P16-P17, vol. 485P. link>1995.
- 1995.
- 1995.
- 1993.
- 1993.
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THE FUNCTIONAL-MORPHOLOGY OF STEREOCILIARY BUNDLES ON COCHLEAR HAIR-CELLS OF THE TURTLE. JOURNAL OF PHYSIOLOGY-LONDON, P352, vol. 467. link>1993.
- 1992.
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BINDING OF A POLYCLONAL ANTIBODY RAISED AGAINST AN AMILORIDE-SENSITIVE NA+ CHANNEL TO GUINEA-PIG COCHLEAR HAIR-CELLS INVITRO IS REDUCED BY DRUGS KNOWN TO AFFECT MECHANOELECTRICAL TRANSDUCTION. JOURNAL OF PHYSIOLOGY-LONDON, P113, vol. 446. link>1992.
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LOCALIZATION OF PUTATIVE MECHANOELECTRICAL TRANSDUCER CHANNELS IN COCHLEAR HAIR-CELLS BY IMMUNOELECTRON MICROSCOPY. SCANNING MICROSCOPY, 741-746, vol. 5(3). link>1991.
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Localisation of putative mechanoelectrical transducer channels in cochlear hair cells by immunoelectron microscopy. Scanning Microsc, 741-745, vol. 5(3). link>1991.
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ANTIBODIES TO AMILORIDE-SENSITIVE SODIUM-CHANNELS REVEAL THE POSSIBLE LOCATION OF THE MECHANOELECTRICAL TRANSDUCER CHANNELS IN GUINEA-PIG COCHLEAR HAIR-CELLS. JOURNAL OF PHYSIOLOGY-LONDON, P124, vol. 438. link>1991.
- 1990.
- 1990.
- 1989.
- 1989.
- 1988.
- 1988.
- 1988.
- 1988.
- 1988.
- 1986.
- 1986.
- 1986.
- 1986.
- 1986.
- 1985.
- 1985.
- 1985.
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MORPHOGENETIC ASPECT OF ASEXUAL DIVISION IN EUDIPLODINIUM-MAGGII. JOURNAL OF PROTOZOOLOGY, A45, vol. 31(4). link>1984.
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MORPHOLOGY OF THE ORAL-REGION IN RUMEN CILIATES. JOURNAL OF PROTOZOOLOGY, A45, vol. 31(4). link>1984.
- 1983.
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ULTRASTRUCTURAL ASPECTS OF ASEXUAL DIVISION IN EUDIPLODINIUM-MAGGII. JOURNAL OF PROTOZOOLOGY, A37, vol. 30(3). link>1983.
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THE STRUCTURE AND MORPHOLOGY OF SHEEP RUMEN CILIATES. JOURNAL OF PROTOZOOLOGY, 322, vol. 29(2). link>1982.
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ULTRASTRUCTURE OF THE RUMEN CILIATE EPIDINIUM-CAUDATUM. JOURNAL OF PROTOZOOLOGY, 636-637, vol. 29(4). link>1982.
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Changes in the distribution of lipoma HMGIC fusion partner-like 5 (Lhfpl5) in mice cochlear hair bundles during development and in the absence of protocadherin 15.2017.
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Ultrastructural organisation and composition of the extracellular matrix surrounding fibrocytes in the spiral ligament of the mouse cochlea.2017.
Chapters
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Hearing and Balance:The vestibular system. In Signals and Perception:The Fundamentals of Human Sensation. Roberts D (Ed.). Palgrave MacMillan, Basingstoke.2002.
Other
- 2009.
- 2009.
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Glutamate transporters around synapses. JOURNAL OF NEUROCHEMISTRY (p. 87, vol. 96). link>2006.
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Comparative uptake of FM1-43 and methylene blue by developing auditory hair cells. British Society of Audiology Short Papers Meetings Abstracts.2004.
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The Effect of Mild Hair-Cell damage and Long-Term Hair-Cell Loss on the Expressoin of the Glutamate Transporter GLAST in the Cochlea. Association for Research in Otolaryngology.2004.
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Tonotopic Differences in Synaptic Release as Measured by Membrane Capacitance Changes in Hair Cells from the Turtle Auditory Papilla. Association for Research in Otolaryngology.2004.
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An investigation of the cochleotopic distributions of GLAST, VGLUT1 and GluR4 in the guinea pig organ of Corti using immuncytochemistry. Abstracts of the 26th Midwinter meeting of the Association for Research in Otolaryngology.2003.
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The relative distribution of $BETA$ and $gamma$-actin isoforms in the guinea-pig organ of Corti.2003.
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Distribution of the Glutamate/Aspartate Transporter GLAST in Relation to the Afferent Synapses of Outer Hair Cells in the Guinea Pig Cochlea. Journal of the Association for Research in Otolaryngology. doi>2001.
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Confocal imaging of alpha-bungarotoxin-tagged acetylcholine receptors in outer hair cells. International Journal of Audiology.2002.
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Factors influencing the distribution of the glutamate-aspartate transporter, GLAST, in the mammalian cochlea. International Journal of Audiology.2002.
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Immunocytochemical investigations of the distribution of calcium buffers in the basilar papilla of the turtle. International Journal of Audiology.2002.
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Immunocytochemical investigations of the distribution of calcium buffers in the basilar papilla of the turtle. International Journal of Audiology.2002.
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Putative cellular targets in autoimmune inner ear disease caused by ulcerative colitis. International Journal of Audiology.2002.
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An immunocytochemical analysis of collagen IV within the mammalian inner ear. British Journal of Audiology.2001.
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Comparative distribution of the glutamate-aspartate transporter GLAST in apical and basal turns of the CD-1 mouse cochlea. British Journal of Audiology.2001.
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The influence of external calcium concentration on the acetylcholine receptor current in mammalian outer hair cells. British Journal of Audiology.2001.
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Regeneration of the mammalian vestibular sensory epithelium following gentamicin-induced damage. J Otolaryngol (pp. 351-360, vol. 29). link>2000.
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Physiological and anatomical investigation of acetylcholine receptor localization in mammalian cochlear outer hair cells. BRITISH JOURNAL OF AUDIOLOGY (pp. 81-82, vol. 34). link>2000.
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The distribution of calmodulin in cochlear hair cells after exposure to high or low extracellular calcium. BRITISH JOURNAL OF AUDIOLOGY (p. 80, vol. 34). link>2000.
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The distribution of collagen IV in the mammalian utricle. BRITISH JOURNAL OF AUDIOLOGY (pp. 82-83, vol. 34). link>2000.
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The composition of linkages between stereocilia. PROCEEDINGS OF THE INTERNATIONAL SYMPOSIUM ON RECENT DEVELOPMENTS IN AUDITORY MECHANICS (pp. 302-306). link>2000.
- 1998.
- 1997.
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Immunocytochemical localization of the high affinity glutamate/aspartate transporter, GLAST, in the rat and guinea-pig cochlea. BRITISH JOURNAL OF AUDIOLOGY (pp. 120-121, vol. 31). link>1997.
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Localization of beta-cytoplasmic actin in guinea pig organ of Corti using post-embedding immunogold labelling. BRITISH JOURNAL OF AUDIOLOGY (pp. 74-75, vol. 31). link>1997.
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Localization of cadherin in guinea-pig organ of Corti using post-embedding immunogold labelling. BRITISH JOURNAL OF AUDIOLOGY (pp. 73-74, vol. 31). link>1997.
- 1996.
- 1990.
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STRUCTURAL ABNORMALITIES IN INNER HAIR-CELLS FOLLOWING KANAMYCIN-INDUCED OUTER HAIR CELL LOSS. MECHANICS AND BIOPHYSICS OF HEARING (pp. 10-17, vol. 87). link>1990.