Modelling MND using human induced pluripotent stem cells

About the project

The main focus of the Chandran lab is regenerative neurology: using patient derived iPSCs to investigate the behaviour of neurons and glial cells of the CNS in neurological diseases. We use state-of-the-art technologies, such CRISPR-Cas9 genome editing and transcriptomics, to interrogate the molecular mechanisms by which mutations in C9ORF72, the most common cause of familial ALS, and TDP43 genes affect motor neurons and the macro-glial cells of the CNS (astrocytes and oligodendrocytes). In particular, we aim to understand the intricate neuron-glial crosstalk in neurodegenerative diseases.

In addition to discovery-based research, we also undertake a translational approach wherein we use automated high-throughput phenotypic evaluation to screen for therapeutic compounds, to develop neuroprotective therapies that target the neurons, as well as the glial cells.

Funder(s)

MND Scotland, The Euan MacDonald Centre

Publication(s)

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
C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca(2+)-permeable AMPA receptor-mediated excitotoxicity
Nat Commun. 2018 Jan 24;9(1):347
Livesey MR, Magnani D, Cleary EM, Vasistha NA, James OT, Selvaraj BT, Burr K, Story D, Shaw CE, Kind PC, Hardingham GE, Wyllie DJ, Chandran S
Maturation and electrophysiological properties of human pluripotent stem cell-derived oligodendrocytes
Stem Cells. 2016 Apr;34(4):1040-53
Serio A, Bilican B, Barmada SJ, Ando DM, Zhao C, Siller R, Burr K, Haghi G, Story D, Nishimura AL, Carrasco MA, Phatnani HP, Shum C, Wilmut I, Maniatis T, Shaw CE, Finkbeiner S, Chandran S
Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy
Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4697-702

Primary location

Edinburgh

Principal Investigator

Other people involved

Dr. Bhuvaneish T. Selvaraj

Dr. Matthew R. Livesey

Dr. Dario Magnani

Dr. Arpan R. Mehta

James D. Cooper


Other lab members who are working on related projects:

Owen. G. James

Dr. Emma Perkins


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