Dr Matthew Livesey
PhD
School of Medicine and Population Health
Research Fellow
+44 114 222 2233
Full contact details
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
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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
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Journal articles
- Genome-wide identification of the genetic basis of amyotrophic lateral sclerosis. Neuron. View this article in WRRO
- 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
- Transactive response DNA-binding protein-43 proteinopathy in oligodendrocytes revealed using an induced pluripotent stem cell model. Brain Communications, 3(4).
- 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
- Oligodendrocyte HCN2 channels regulate myelin sheath length. The Journal of Neuroscience. View this article in WRRO
- Altered network properties in C9ORF72 repeat expansion cortical neurons are due to synaptic dysfunction. Molecular Neurodegeneration, 16(1).
- Cortical neurons derived from human pluripotent stem cells lacking FMRP display altered spontaneous firing patterns. Molecular Autism, 11(1).
- Neuronal activity disrupts myelinated axon integrity in the absence of NKCC1b. Journal of Cell Biology, 219(7). View this article in WRRO
- Dysregulation of AMPA receptor subunit expression in sporadic ALS post‐mortem brain. The Journal of Pathology, 250(1), 67-78.
- Spatial transcriptomics identifies spatially dysregulated expression of
GRM3
and
USP47
in amyotrophic lateral sclerosis. Neuropathology and Applied Neurobiology, 46(5), 441-457.
- Transplanted t(1;11) patient-derived OPCs form shorter myelin internodes in the hypomyelinated shiverer mice. Molecular Psychiatry, 24(11), 1567-1567.
- Myelinated axon physiology and regulation of neural circuit function. Glia, 67(11), 2050-2062.
- Familial t(1;11) translocation is associated with disruption of white matter structural integrity and oligodendrocyte–myelin dysfunction. Molecular Psychiatry, 24(11), 1641-1654.
- 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.
- C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable AMPA receptor-mediated excitotoxicity. Nature Communications, 9(1).
- Selective inhibition of extra-synaptic α5-GABA A receptors by S44819, a new therapeutic agent. Neuropharmacology, 125, 353-364.
- Modeling the C9ORF72
repeat expansion mutation using human induced pluripotent stem cells. Brain Pathology, 27(4), 518-524.
- 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.
- Functional properties ofin vitroexcitatory cortical neurons derived from human pluripotent stem cells. The Journal of Physiology, 594(22), 6573-6582.
- Author response: Evidence for evolutionary divergence of activity-dependent gene expression in developing neurons.
- Modeling ALS with motor neurons derived from human induced pluripotent stem cells. Nature Neuroscience, 19(4), 542-553.
- Maturation and electrophysiological properties of human pluripotent stem cell-derived oligodendrocytes. STEM CELLS, 34(4), 1040-1053.
- Hypothermic modulation of human cortical neurons to explore a role for tau protein in neuroprotection. The Lancet, 387, S88-S88.
- Hypothermic Preconditioning Reverses Tau Ontogenesis in Human Cortical Neurons and is Mimicked by Protein Phosphatase 2A Inhibition. EBioMedicine, 3, 141-154.
- Ionotropic GABA and glycine receptor subunit composition in human pluripotent stem cell‐derived excitatory cortical neurones. The Journal of Physiology, 592(19), 4353-4363.
- Generation of Functional Neurons from Feeder-Free, Keratinocyte-Derived Equine Induced Pluripotent Stem Cells. Stem Cells and Development, 23(13), 1524-1534.
- Maturation of AMPAR Composition and the GABAAR Reversal Potential in hPSC-Derived Cortical Neurons. Journal of Neuroscience, 34(11), 4070-4075.
- Mutagenic Analysis of the Intracellular Portals of the Human 5-HT3A Receptor. Journal of Biological Chemistry, 288(44), 31592-31601.
- Influence of GluN2 subunit identity on NMDA receptor function. Neuropharmacology, 74, 4-17.
- TCN 201 selectively blocks GluN2A-containing NMDARs in a GluN1 co-agonist dependent but non-competitive manner. Neuropharmacology, 63(3), 441-449.
- 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.
- Rings of Charge within the Extracellular Vestibule Influence Ion Permeation of the 5-HT3A Receptor. Journal of Biological Chemistry, 286(18), 16008-16017.
- 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.
- Structural Determinants of Ca2+Permeability and Conduction in the Human 5-Hydroxytryptamine Type 3A Receptor. Journal of Biological Chemistry, 283(28), 19301-19313.
- 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.
- Dynamic Modification of a Mutant Cytoplasmic Cysteine Residue Modulates the Conductance of the Human 5-HT3AReceptor. Journal of Biological Chemistry, 282(9), 6172-6182.
- Novel structural determinants of single-channel conductance in nicotinic acetylcholine and 5-hydroxytryptamine type-3 receptors. Biochemical Society Transactions, 34(5), 882-886.
- Importin 13-dependent axon diameter growth regulates conduction speeds along myelinated CNS axons. Nature Communications.
- An interaction between synapsin and C9orf72 regulates excitatory synapses and is impaired in ALS/FTD. Acta Neuropathologica.
- SPG15 protein deficits are at the crossroads between lysosomal abnormalities, altered lipid metabolism and synaptic dysfunction. Human Molecular Genetics.
- Central nervous system hypomyelination disrupts axonal conduction and behaviour in larval zebrafish. The Journal of Neuroscience.
- 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.
- Familial t(1;11) translocation is associated with disruption of white matter structural integrity and oligodendrocyte-myelin dysfunction.
- Evidence for evolutionary divergence of activity-dependent gene expression in developing neurons. eLife, 5.
Chapters
- In Vitro Generation and Electrophysiological Characterization of OPCs and Oligodendrocytes from Human Pluripotent Stem Cells, Oligodendrocytes (pp. 65-77). Springer New York
Preprints
- Profiling human hypothalamic neurons reveals a candidate combination drug therapy for weight loss, Cold Spring Harbor Laboratory.
- Importin 13-dependent Axon Diameter Growth Regulates Conduction Speeds along Myelinated CNS Axons, Cold Spring Harbor Laboratory.
- Central nervous system hypomyelination disrupts axonal conduction and behaviour in larval zebrafish, Cold Spring Harbor Laboratory.
- Safety and efficacy of C9ORF72-repeat RNA nuclear export inhibition in amyotrophic lateral sclerosis, Cold Spring Harbor Laboratory.
- Disruption to NKCC1 impairs the response of myelinating Schwann cells to neuronal activity and leads to severe peripheral nerve pathology, Cold Spring Harbor Laboratory.
- Genome-wide identification of the genetic basis of amyotrophic lateral sclerosis. Neuron. View this article in WRRO
- 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
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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
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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.