Prof Thomas Gillingwater
BSc, MBA, PhD, FRMS, FAS
Professor of Neuroanatomy
University of Edinburgh
Centre for Integrative Physiology & Euan MacDonald Centre for Motor Neurone Disease Resarch
Old Medical School, Teviot Place, Edinburgh, EH8 9XD
Telephone: 44 (0) 131 650 3724
Click for a 1-page printable CV
Lecturer in Anatomy, School of Biomedical Sciences, University of Edinburgh (2004)
MBA, University of Edinburgh (2006)
PhD in Neuroscience, University of Edinburgh (2001)
BSc (Hons) in Human Biology, University of Leeds
Principle Teaching Responsibilities: Human Gross Anatomy & Neuroanatomy (MBChB) and Course Director for Anatomy & Pathology 2 (BSc Medical Sciences)
Editot in Chief - Journal of Anatomy (2011-present )
Academic Editor - PLoS One (2011-present )
Research OverviewRecent advances in neurobiological research have demonstrated that axonal and synaptic compartments of neurons are capable of independently regulating their own development, stabilization and degeneration. These findings have significant implications for many neurodegenerative diseases including motor neuron disease, Batten disease and Alzheimer’s disease where axons and synapses are now regarded as primary pathological targets.
Our research aims to identify the incidence and importance of axon/synapse-specific regulation of neuronal form and function in the developing, normal and degenerating nervous system. We combine quantitative imaging (confocal and electron microscopy) and molecular biology techniques to study the structure and function of axons and synapses from the central and peripheral nervous systems, both in vivo and in vitro.
At present the lab is concentrating on two main research areas. First, we are examining the cellular and molecular pathways that regulate synaptic and axonal vulnerability in several mouse models of motor neuron disease (including Spinal Muscular Atrophy [SMA] and Amyotrophic Lateral Sclerosis [ALS]) and Batten disease. And second, we are attempting to identify novel therapeutic strategies for the treatment of neurodegenerative diseases in humans with axonal and/or synaptic involvement. In particular, we are investigating the mechanism of action, and therapeutic value, of a spontaneous, neuroprotective genetic mutation known as Wallerian Degeneration-Slow (Wlds).
Other Members in the GroupGillian Hamilton
CollaboratorsJ. Cooper: Institute of Psychiatry, King's College London
M. Freeman:University of Massachusetts
. Robinson:University of Plymouth
K. Talbot: University of Oxford
J. Tyynela: University of Helsinki
B. Wirth: University of Cologne
GrantsMuscular Dystrophy Campaign (MDC)
Sylvia Aitken Charitable Trust
Select Recent Publications
Kay K, Smith C, Wright AK, Serrano-Pozo A, Pooler A, Koffie R, Bastin ME, Bak TH, Abrahams S, Kopeikina KJ, Frosch M, Gillingwater TH, Hyman BT & Spires-Jones TL (2013) Studying synapses in human brain with array tomography and electron microscopy. Nature Protocols In Press.
Hamilton G & Gillingwater TH (2013) Spinal muscular atrophy: going beyond the motor neuron. Trends in Molecular Medicine 19:40-50.
Simpson AH, Gillingwater TH, Anderson H, Cottrell D, Sherman DL, Ribchester RR & Brophy PJ (2013) Effect of limb lengthening on internodal length and conduction velocity of peripheral nerve. Journal of Neuroscience 33:4536-4539.
Wishart TM, Rooney T, Lamont DJ, Wright AK, Morton AJ, Jackson M, Freeman MR & Gillingwater TH (2012) Combining Comparative Proteomics and Molecular Genetics Uncovers Regulators of Synaptic and Axonal Stability and Degeneration In Vivo. PLoS Genetics 8:e1002936.
Avery M, Rooney TM, Pandya JD, Wishart TM, Gillingwater TH, Geddes JW, Sullivan P & Freeman MR (2012) WldS prevents axon degeneration through increased mitochondrial flux and enhanced mitochondrial Ca2+ buffering. Current Biology 22:596-600.
Mutsaers CA, Wishart TM, Lamont DJ, Riessland M, Schreml J, Comley LH, Murray LM, Parson SH, Lochmüller H, Wirth B, Talbot K, Gillingwater TH (2011) Reversible molecular pathology of skeletal muscle in spinal muscular atrophy. Human Molecular Genetics 20:4334-4344.
Patani R, Hollins AJ, Wishart TM, Puddifoot CA, Alvarez S, de Lera AR, Wyllie DJ, Compston DA, Pedersen RA, Gillingwater TH, Hardingham GE, Allen ND, Chandran S (2011) Retinoid-independent motor neurogenesis from human embryonic stem cells reveals a medial columnar ground state. Nature Communications 2:214.
Comley LH, Fuller HR, Wishart TM, Mutsaers CA, Thomson D, Wright AK, Morris GE, Parson SH, Horsburgh K, Gillingwater TH (2011) ApoE isoform-specific regulation of regeneration in the peripheral nervous system. Human Molecular Genetics 20:2406-2421.
Key Earlier Publications
Wishart TM, Huang J P-W, Murray LM, Lamont DJ, Mutsaers CA, Ross J, Geldsetzer P, Ansorge O, Talbot K, Parson SH, Gillingwater TH (2010) SMN deficiency disrupts brain development in a mouse model of severe spinal muscular atrophy. Human Molecular Genetics 19:4216-4228.
Murray LM, Lee S, Baumer D, Parson SH, Talbot K, Gillingwater TH (2010) Pre-symptomatic development of lower motor neuron connectivity in a mouse model of severe spinal muscular atrophy. Human Molecular Genetics 19:420-433.
de Waard MC, van der Pluijm I, Zuiderveen Borgesius N, Comley LH, Haasdijk ED, Rijksen Y, Ridwan Y, Zondag G, Hoeijmakers JH, Elgersma Y, Gillingwater TH, Jaarsma D (2010) Age-related motor neuron degeneration in DNA repair-deficient Ercc1 mice. Acta Neuropathologica 120:461-475.
Bäumer D, Lee S, Nicholson G, Davies JL, Parkinson NJ, Murray LM, Gillingwater TH, Ansorge O, Davies KE, Talbot K (2009) Alternative splicing events are a late feature of pathology in a mouse model of spinal muscular atrophy. PLoS Genetics 5:e1000773.
Kielar C, Wishart TM, Palmer A, Dihanich S, Wong AM, Macauley SL, Chun C-H, Sands MS, Pearce D, Cooper JD & Gillingwater TH (2009) Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease. Human Molecular Genetics 18:4066-4080.
Murray LM, Comley LH, Thomson D, Parkinson N, Talbot K, Gillingwater TH (2008) Selective vulnerability of motor neurons and dissociation of pre- and post-synaptic pathology at the neuromuscular junction in mouse models of spinal muscular atrophy. Human Molecular Genetics 17:949-962.
Wishart TM, Pemberton HN, James SR, McCabe CJ & Gillingwater TH (2008) Modified cell cycle status in a mouse model of altered neuronal vulnerability (Wallerian Degeneration Slow; Wlds). Genome Biology 9(6):R101.
Wishart TM, Paterson JM, Short DM, Meredith S, Robertson KA, Sutherland C, Cousin MA, Dutia MB, Gillingwater TH (2007) Differential proteomics analysis of synaptic proteins identifies potential cellular targets and protein mediators of synaptic neuroprotection conferred by the slow Wallerian degeneration (Wlds) gene. Molecular & Cellular Proteomics 6:1318-1330.
Gillingwater TH, Ingham CA, Parry KE, Wright AK, Haley JE, Wishart TM, Arbuthnott GW, Ribchester RR (2006) Delayed synaptic degeneration in the CNS of Wlds mice after cortical lesion. Brain 129:1546-1556.
Mi W, Beirowski B, Gillingwater TH, Adalbert R, Wagner D, Grumme D, Osaka H, Conforti L, Arnhold S, Addicks K, Wada K, Ribchester RR, Coleman MP (2005) The slow Wallerian degeneration gene, WldS, inhibits axonal spheroid pathology in gracile axonal dystrophy mice. Brain 128:405-416.
Nishimura AL, Mitne-Neto M, Silva HCA, Richieri-Costa A, Middleton S, Cascio D, Kok F, Oliveira JRM, Gillingwater T, Webb J, Skehel P, Zatz M (2004) A mutation in the vesicle trafficking protein VAP-B causes late onset spinal muscular atrophy and amyotrophic lateral sclerosis. American Journal of Human Genetics 75:822-831.
Mack TG, Reiner M, Beirowski B, Mi W, Emanuelli M, Wagner D, Thomson D, Gillingwater T, Court F, Conforti L, Fernando FS, Tarlton A, Andressen C, Addicks K, Magni G, Ribchester RR, Perry VH, Coleman MP (2001) Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene. Nature Neuroscience 4:1199-1206.
A full list of publications is available here.