Dr Matthew Livesey

PhD

Neuroscience, School of Medicine and Population Health

Research Fellow

M.R.Livesey@Sheffield.ac.uk
+44 114 222 2233

Sheffield Institute for Translational Neuroscience (SITraN)

Full contact details

Dr Matthew Livesey
Neuroscience, School of Medicine and Population Health
Sheffield Institute for Translational Neuroscience (SITraN)
385a Glossop Road
Sheffield
S10 2HQ

Profile

I studied Pharmacology (B.Sc. Hons) at the University of Edinburgh between 2001 – 2005. In 2005, I joined the Department of Neuroscience, University of Dundee, to undertake a BBSRC-Case PhD studentship. Here, using patch-clamp electrophysiology techniques, I examined the structure-function of pentameric ligand-gated ion channels. My time in Dundee included a short post-doctoral position (JBC, 2008 and JBC, 2011).

I joined the University of Edinburgh at the start of 2011 and undertook a postdoctoral position to examine the functional capabilities and developmental properties of pluripotent stem cell-derived cortical neurons (J.Neurosci, 2014; J.Physiol, 2014 and PLoS One, 2014). In this time I became interested in using this technology in order to model disease, specifically amyotrophic lateral sclerosis and frontotemporal dementia, and was awarded a Royal Society of Edinburgh Fellowship (2015) in order to investigate synaptic impairments in ALS-FTD (Nature Neuroscience, 2016; Nature Communications, 2018; J.Pathology, 2020; Molecular Neurodegeneration, 2021). Furthermore, noting the increasing appreciation of the roles of non-neuronal cell types in healthy neuronal health and disease, I have also explored the functional properties of oligodendrocytes-derived from ALS patients (Stem Cells, 2016) and also began to examine the heavily underexplored area of oligodendrocyte physiology (Glia, 2019; Journal of Neuroscience, 2021).

In March 2020, I arrived at SITraN as a principle investigator to lead work on neurophysiological perturbations and their mechanistic bases in ALS-FTD.

Research interests

In neurodegenerative disease, neuronal dysfunction precedes neuronal death. My research interests centre around understanding these functional disturbances in neurons. Furthermore, it is increasingly regarded that such diseases are not ‘purely’ neuronal and often include a role for their supporting cells called glia. Our research also therefore investigates the properties of glia; both their functional properties and their role on neuronal function.

To do this we combine multiple research specialisations; electrophysiology, human in vitro cell models and rodent models.

Current Projects

Glutamatergic dysfunction in ALS patient-derived neurons and glia.
Synaptic pathophysiology in cortical neurons derived from ALS patients.
The physiological role of C9ORF72.
The role of ion channels on oligodendrocyte-lineage cell function.

Publications

Journal articles

Zhang S, Cooper-Knock J, Weimer AK, Shi M, Moll T, Marshall JNG, Harvey C, Nezhad HG, Franklin J, Souza CDS , Ning K et al (2022) Genome-wide identification of the genetic basis of amyotrophic lateral sclerosis. Neuron. View this article in WRRO
Pasniceanu I-S, Atwal MS, Souza CDS, Ferraiuolo L & Livesey MR (2021) Emerging mechanisms underpinning neurophysiological impairments in C9ORF72 repeat expansion-mediated amyotrophic lateral sclerosis/frontotemporal dementia. Frontiers in Cellular Neuroscience, 15. View this article in WRRO
Barton SK, Magnani D, James OG, Livesey MR, Selvaraj BT, James OT, Perkins EM, Gregory JM, Cleary E, Ausems CRM , Carter R et al (2021) Transactive response DNA-binding protein-43 proteinopathy in oligodendrocytes revealed using an induced pluripotent stem cell model. Brain Communications, 3(4).
Castelli LM, Cutillo L, Souza CDS, Sanchez-Martinez A, Granata I, Lin Y-H, Myszczynska MA, Heath PR, Livesey MR, Ning K , Azzouz M et al (2021) SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export : genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis. Molecular Neurodegeneration, 16(1). View this article in WRRO
Swire M, Assinck P, McNaughton PA, Lyons DA, ffrench-Constant C & Livesey MR (2021) Oligodendrocyte HCN2 channels regulate myelin sheath length. The Journal of Neuroscience. View this article in WRRO
Perkins EM, Burr K, Banerjee P, Mehta AR, Dando O, Selvaraj BT, Suminaite D, Nanda J, Henstridge CM, Gillingwater TH , Hardingham GE et al (2021) Altered network properties in C9ORF72 repeat expansion cortical neurons are due to synaptic dysfunction. Molecular Neurodegeneration, 16(1).
Das Sharma S, Pal R, Reddy BK, Selvaraj BT, Raj N, Samaga KK, Srinivasan DJ, Ornelas L, Sareen D, Livesey MR , Bassell GJ et al (2020) Cortical neurons derived from human pluripotent stem cells lacking FMRP display altered spontaneous firing patterns. Molecular Autism, 11(1).
Marshall-Phelps KLH, Kegel L, Baraban M, Ruhwedel T, Almeida RG, Rubio-Brotons M, Klingseisen A, Benito-Kwiecinski SK, Early JJ, Bin JM , Suminaite D et al (2020) Neuronal activity disrupts myelinated axon integrity in the absence of NKCC1b. Journal of Cell Biology, 219(7). View this article in WRRO
Gregory JM, Livesey MR, McDade K, Selvaraj BT, Barton SK, Chandran S & Smith C (2020) Dysregulation of AMPA receptor subunit expression in sporadic ALS post‐mortem brain. The Journal of Pathology, 250(1), 67-78.
Gregory JM, McDade K, Livesey MR, Croy I, Marion de Proce S, Aitman T, Chandran S & Smith C (2020) Spatial transcriptomics identifies spatially dysregulated expression of GRM3 and USP47 in amyotrophic lateral sclerosis. Neuropathology and Applied Neurobiology, 46(5), 441-457.
Vasistha NA, Johnstone M, Barton SK, Mayerl SE, Thangaraj Selvaraj B, Thomson PA, Dando O, Grünewald E, Alloza C, Bastin ME , Livesey MR et al (2019) Transplanted t(1;11) patient-derived OPCs form shorter myelin internodes in the hypomyelinated shiverer mice. Molecular Psychiatry, 24(11), 1567-1567.
Suminaite D, Lyons DA & Livesey MR (2019) Myelinated axon physiology and regulation of neural circuit function. Glia, 67(11), 2050-2062.
Vasistha NA, Johnstone M, Barton SK, Mayerl SE, Thangaraj Selvaraj B, Thomson PA, Dando O, Grünewald E, Alloza C, Bastin ME , Livesey MR et al (2019) Familial t(1;11) translocation is associated with disruption of white matter structural integrity and oligodendrocyte–myelin dysfunction. Molecular Psychiatry, 24(11), 1641-1654.
Johnstone M, Vasistha NA, Barbu MC, Dando O, Burr K, Christopher E, Glen S, Robert C, Fetit R, Macleod KG , Livesey MR et al (2019) Reversal of proliferation deficits caused by chromosome 16p13.11 microduplication through targeting NFκB signaling: an integrated study of patient-derived neuronal precursor cells, cerebral organoids and in vivo brain imaging. Molecular Psychiatry, 24(2), 294-311.
Selvaraj BT, Livesey MR, Zhao C, Gregory JM, James OT, Cleary EM, Chouhan AK, Gane AB, Perkins EM, Dando O , Lillico SG et al (2018) C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable AMPA receptor-mediated excitotoxicity. Nature Communications, 9(1).
Etherington L-A, Mihalik B, Pálvölgyi A, Ling I, Pallagi K, Kertész S, Varga P, Gunn BG, Brown AR, Livesey MR , Monteiro O et al (2017) Selective inhibition of extra-synaptic α5-GABA A receptors by S44819, a new therapeutic agent. Neuropharmacology, 125, 353-364.
Selvaraj BT, Livesey MR & Chandran S (2017) Modeling the C9ORF72 repeat expansion mutation using human induced pluripotent stem cells. Brain Pathology, 27(4), 518-524.
Johnstone M, Vasistha N, Livesey M, Burr K, Whalley H, Clair DS, Blackwood D, Wyllie D, Lawrie S, Johnstone EC , McIntosh AM et al (2017) Modelling a Genetic Risk for Schizophrenia in Human Induced Pluripotent Stem Cells (Ipscs): Phenotypic Differences in Patients with Mutations in Nde1. European Neuropsychopharmacology, 27, S509-S510.
Livesey MR, Magnani D, Hardingham GE, Chandran S & Wyllie DJA (2016) Functional properties ofin vitroexcitatory cortical neurons derived from human pluripotent stem cells. The Journal of Physiology, 594(22), 6573-6582.
Qiu J, McQueen J, Bilican B, Dando O, Magnani D, Punovuori K, Selvaraj BT, Livesey M, Haghi G, Heron S , Burr K et al (2016) Author response: Evidence for evolutionary divergence of activity-dependent gene expression in developing neurons.
Sances S, Bruijn LI, Chandran S, Eggan K, Ho R, Klim JR, Livesey MR, Lowry E, Macklis JD, Rushton D , Sadegh C et al (2016) Modeling ALS with motor neurons derived from human induced pluripotent stem cells. Nature Neuroscience, 19(4), 542-553.
Livesey MR, Magnani D, Cleary EM, Vasistha NA, James OT, Selvaraj BT, Burr K, Story D, Shaw CE, Kind PC , Hardingham GE et al (2016) Maturation and electrophysiological properties of human pluripotent stem cell-derived oligodendrocytes. STEM CELLS, 34(4), 1040-1053.
Rzechorzek NM, Connick P, Livesey MR, Borooah S, Patani R, Burr K, Story D, Wyllie DJA, Hardingham GE & Chandran S (2016) Hypothermic modulation of human cortical neurons to explore a role for tau protein in neuroprotection. The Lancet, 387, S88-S88.
Rzechorzek NM, Connick P, Livesey MR, Borooah S, Patani R, Burr K, Story D, Wyllie DJA, Hardingham GE & Chandran S (2016) Hypothermic Preconditioning Reverses Tau Ontogenesis in Human Cortical Neurons and is Mimicked by Protein Phosphatase 2A Inhibition. EBioMedicine, 3, 141-154.
James OT, Livesey MR, Qiu J, Dando O, Bilican B, Haghi G, Rajan R, Burr K, Hardingham GE, Chandran S , Kind PC et al (2014) Ionotropic GABA and glycine receptor subunit composition in human pluripotent stem cell‐derived excitatory cortical neurones. The Journal of Physiology, 592(19), 4353-4363.
Sharma R, Livesey MR, Wyllie DJA, Proudfoot C, Whitelaw CBA, Hay DC & Donadeu FX (2014) Generation of Functional Neurons from Feeder-Free, Keratinocyte-Derived Equine Induced Pluripotent Stem Cells. Stem Cells and Development, 23(13), 1524-1534.
Livesey MR, Bilican B, Qiu J, Rzechorzek NM, Haghi G, Burr K, Hardingham GE, Chandran S & Wyllie DJA (2014) Maturation of AMPAR Composition and the GABAAR Reversal Potential in hPSC-Derived Cortical Neurons. Journal of Neuroscience, 34(11), 4070-4075.
Carland JE, Cooper MA, Livesey MR, Hales TG, Peters JA & Lambert JJ (2013) Mutagenic Analysis of the Intracellular Portals of the Human 5-HT3A Receptor. Journal of Biological Chemistry, 288(44), 31592-31601.
Wyllie DJA, Livesey MR & Hardingham GE (2013) Influence of GluN2 subunit identity on NMDA receptor function. Neuropharmacology, 74, 4-17.
Edman S, McKay S, MacDonald LJ, Samadi M, Livesey MR, Hardingham GE & Wyllie DJA (2012) TCN 201 selectively blocks GluN2A-containing NMDARs in a GluN1 co-agonist dependent but non-competitive manner. Neuropharmacology, 63(3), 441-449.
Chia PW, Livesey MR, Slawin AMZ, van Mourik T, Wyllie DJA & O'Hagan D (2012) 3-Fluoro-N-methyl-D-aspartic acid (3F-NMDA) Stereoisomers as Conformational Probes for Exploring Agonist Binding at NMDA Receptors. Chemistry - A European Journal, 18(28), 8813-8819.
Livesey MR, Cooper MA, Lambert JJ & Peters JA (2011) Rings of Charge within the Extracellular Vestibule Influence Ion Permeation of the 5-HT3A Receptor. Journal of Biological Chemistry, 286(18), 16008-16017.
Peters JA, Cooper MA, Carland JE, Livesey MR, Hales TG & Lambert JJ (2010) Novel structural determinants of single channel conductance and ion selectivity in 5-hydroxytryptamine type 3 and nicotinic acetylcholine receptors. The Journal of Physiology, 588(4), 587-596.
Livesey MR, Cooper MA, Deeb TZ, Carland JE, Kozuska J, Hales TG, Lambert JJ & Peters JA (2008) Structural Determinants of Ca2+Permeability and Conduction in the Human 5-Hydroxytryptamine Type 3A Receptor. Journal of Biological Chemistry, 283(28), 19301-19313.
Chen PE, Geballe MT, Katz E, Erreger K, Livesey MR, O'Toole KK, Le P, Lee CJ, Snyder JP, Traynelis SF & Wyllie DJA (2008) Modulation of glycine potency in rat recombinant NMDA receptors containing chimeric NR2A/2D subunits expressed inXenopus laevisoocytes. The Journal of Physiology, 586(1), 227-245.
Deeb TZ, Carland JE, Cooper MA, Livesey MR, Lambert JJ, Peters JA & Hales TG (2007) Dynamic Modification of a Mutant Cytoplasmic Cysteine Residue Modulates the Conductance of the Human 5-HT3AReceptor. Journal of Biological Chemistry, 282(9), 6172-6182.
Peters JA, Carland JE, Cooper MA, Livesey MR, Deeb TZ, Hales TG & Lambert JJ (2006) Novel structural determinants of single-channel conductance in nicotinic acetylcholine and 5-hydroxytryptamine type-3 receptors. Biochemical Society Transactions, 34(5), 882-886.
Bin J, Suminaite D, Benito-Kwiecinski S, Kegel L, Rubio-Brotons M, Early J, Soong D, Livesey M, Poole R & Lyons D () Importin 13-dependent axon diameter growth regulates conduction speeds along myelinated CNS axons. Nature Communications.
Bauer CS, Cohen RN, Sironi F, Livesey MR, Gillingwater TH, Highley JR, Fillingham DJ, Coldicott I, Smith EF, Gibson YB , Webster CP et al () An interaction between synapsin and C9orf72 regulates excitatory synapses and is impaired in ALS/FTD. Acta Neuropathologica.
Marrone L, Marchi PM, Webster CP, Marroccella R, Coldicott I, Reynolds S, Alves-Cruzeiro J, Yang Z-L, Higginbottom A, Khundadze M , Shaw PJ et al () SPG15 protein deficits are at the crossroads between lysosomal abnormalities, altered lipid metabolism and synaptic dysfunction. Human Molecular Genetics.
Madden ME, Suminaite D, Ortiz E, Early JE, Koudelka S, Livesey MR, Bianco IH, Granato M & Lyons DA () Central nervous system hypomyelination disrupts axonal conduction and behaviour in larval zebrafish. The Journal of Neuroscience.
Bilican B, Livesey MR, Haghi G, Qiu J, Burr K, Siller R, Hardingham GE, Wyllie DJA & Chandran S () Physiological Normoxia and Absence of EGF Is Required for the Long-Term Propagation of Anterior Neural Precursors from Human Pluripotent Cells. PLoS ONE, 9(1), e85932-e85932.
Vasistha NA, Johnstone M, Barton SK, Mayerl S, Selvaraj BT, Thomson PA, Dando O, Grünewald E, Alloza C, Bastin ME , Livesey MR et al () Familial t(1;11) translocation is associated with disruption of white matter structural integrity and oligodendrocyte-myelin dysfunction.
Qiu J, McQueen J, Bilican B, Dando O, Magnani D, Punovuori K, Selvaraj BT, Livesey M, Haghi G, Heron S , Burr K et al () Evidence for evolutionary divergence of activity-dependent gene expression in developing neurons. eLife, 5.

Chapters

Magnani D, Chandran S, Wyllie DJA & Livesey MR (2019) In Vitro Generation and Electrophysiological Characterization of OPCs and Oligodendrocytes from Human Pluripotent Stem Cells, Oligodendrocytes (pp. 65-77). Springer New York

Preprints

Chen H-JC, Yang A, Mazzaferro S, Mali I, Cahn O, Kentistou K, Rowley C, Stewart N, Seah JWE, Pisupati V , Kirwan P et al (2023) Profiling human hypothalamic neurons reveals a candidate combination drug therapy for weight loss, Cold Spring Harbor Laboratory.
Bin JM, Suminaite D, Benito-Kwiecinski SK, Kegel L, Rubio-Brotons M, Early JJ, Soong D, Livesey MR, Poole RJ & Lyons DA (2023) Importin 13-dependent Axon Diameter Growth Regulates Conduction Speeds along Myelinated CNS Axons, Cold Spring Harbor Laboratory.
Madden ME, Suminaite D, Ortiz E, Early JJ, Koudelka S, Livesey MR, Bianco IH, Granato M & Lyons DA () Central nervous system hypomyelination disrupts axonal conduction and behaviour in larval zebrafish, Cold Spring Harbor Laboratory.
Castelli LM, Cutillo L, Souza CDS, Sanchez-Martinez A, Granata I, Myszczynska MA, Heath PR, Livesey MR, Ning K, Azzouz M , Shaw PJ et al () Safety and efficacy of C9ORF72-repeat RNA nuclear export inhibition in amyotrophic lateral sclerosis, Cold Spring Harbor Laboratory.
Kegel L, Marshall-Phelps KLH, Baraban M, Almeida RG, Rubio-Brotons M, Klingseisen A, Benito-Kwiecinski S, Early JJ, Bin J, Livesey MR , Poole RJ et al () Disruption to NKCC1 impairs the response of myelinating Schwann cells to neuronal activity and leads to severe peripheral nerve pathology, Cold Spring Harbor Laboratory.

Research group

Ms Iris Pasniceanu (PhD student)
Mr Manpreet Atwal (PhD student)
Ms Marilina Douloudi (PhD Student)

Research Lab Alumni (including current position where known)
Ms Niamh Conway (MSc student)
Ms Zahra Shather (MSc student, Research assistant at Samsara Therapeutics)
Ms Ergita Bali (Technician, PhD student at University of Sheffield)
Ms Amelia Potter (MSc student)

Grants

The lab is currently funded by the following sources;

Motor Neurone Disease Association
MRC
Industrial collaboration with MSD

Previous funders

ARUK
Royal Society
Rosetrees Trust

Professional activities and memberships

Internal:

Post-graduate research tutor
MSc teaching

External:

Peer reviewer for journals including Nature Communications, Cell Reports, Journal of Neuroscience and Journal of Physiology.
Peer reviewer for grant funding bodies including MRC, BBSRC, NC3Rs, MNDA and ARUK.

School of Medicine and Population Health