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 predominantly combine two research specialisations; electrophysiology and in vitro cell models, including human stem cell technology and primary cell culture.
- 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.
Gregory JM*, Livesey MR*, McDade K, Selvaraj BT, Barton S, Chandran S, Smith C. (2020). Calcium permeable AMPA receptor subunit dysregulation in in sporadic ALS patients. J.Pathol. 250:67-78.
Selvaraj BT*, Livesey MR*, Zhao C, Gregory JM, James OT, Cleary EM, Chouhan AK, Gane AB, Perkins EM, Dando O, Lillico SG, Lee YB, Nishimura AL, Poreci U, Thankamony S, Pray M, Vasistha NA, Magnani D, Borooah S, Burr K, Story D, McCampbell A, Shaw CE, Kind PC, Aitman TJ, Whitelaw CBA, Wilmut I, Smith C, Miles GB, Hardingham GE, Wyllie DJA, Chandran S. (2018) C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable AMPA receptor-mediated excitotoxicity. Nature Comms. 9:347.
Sances S, Bruijn LI, Chandran S, Eggan K, Ho R, Klim JR, Livesey MR, Lowry E, Macklis JD, Rushton D, Sadegh C, Sareen D, Wichterle H, Zhang SC, Svendsen CN. (2016) Modeling ALS with motor neurons derived from induced pluripotent stem cells. Nature Neuroscience. 16: 542-553.
Livesey MR*, Magnani D*, Cleary E, Vasistha NA, James OT, Selvaraj BT, Burr K, Story D, Shaw CE, Hardingham GE, Wyllie DJ, Chandran S. (2016). Maturation and electrophysiological properties of human pluripotent stem cell-derived oligodendrocytes. Stem Cells. 34: 1040-1053.
Livesey MR*, Bilican B*, Qiu J, Rzechorzek NM, Haghi G, Burr K, Hardingham GE, Chandran S, Wyllie DJ. (2014). Maturation of AMPAR composition and the GABAAR reversal potential in hPSC-derived cortical neurons. J. Neurosci. 34: 4070-4075.
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.
I studied Pharmacology (B.Sc. Hons) at the University of Edinburgh between 2001 – 2005. I undertook my undergraduate project at the, then, Centre for Integrative Physiology, under the supervision of Prof. David Wyllie, with whom I developed a strong interest in electrophysiology and the functional nature of ion channels.
In 2005, I joined the Department of Neuroscience, University of Dundee, to undertake a BBSRC-Case PhD studentship under the supervision of Professor’s John Peters and Jeremy Lambert. 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 in the laboratories of Professors David Wyllie, Giles Hardingham and Siddharthan Chandran 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 amytrophic lateral sclerosis and frontotemporal dementia, and was awarded a Royal Society of Edinburgh Fellowship (2015) in order to develop and continue this research line (Nature Neuroscience, 2016; Nature Communications, 2018 and J.Pathology, 2020). 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).
In March 2020, I arrived at SITraN as a principle investigator to lead work on neurophysiological perturbations and their mechanistic bases in neurological disease.
Department of Neuroscience
University of Sheffield
385a Glossop Road
T: +44 (0) 114 2222233