Contact information
David Gordon
Senior Scientist
Utilising a high throughput screening pipeline to identify drugs promoting survival in ALS motor neurons
My research is focused on using mouse models to understand the mechanisms underlying motor neuron loss in amyotrophic lateral sclerosis (ALS). My ultimate aim is to identify new pathways driving ALS, or drugs that can improve translational outcomes for people living with the disease. I am particularly interested in the role of a protein called TDP-43, in which the presence of mutations drive onset and progression of ALS, as well as the adverse effects of oxidative stress on motor neuron loss.
Most recently we have utilised a cell culture model in which an ALS-associated mutant human TDP-43 is expressed in mouse embryonic stem cells, which can then be programmed to become motor neurons in vitro. Using these cells as a drug-discovery platform in high throughput screens, we have identified several pro-survival drugs, and are currently validating candidate drugs in our mouse and human cell culture models.
Recent publications
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An ALS-linked mutation in TDP-43 disrupts normal protein interactions in the motor neuron response to oxidative stress.
Journal article
Feneberg E. et al, (2020), Neurobiol Dis, 144
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Mice Carrying ALS Mutant TDP-43, but Not Mutant FUS, Display In Vivo Defects in Axonal Transport of Signaling Endosomes.
Journal article
Sleigh JN. et al, (2020), Cell Rep, 30, 3655 - 3662.e2
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Neuronal over-expression of Oxr1 is protective against ALS-associated mutant TDP-43 mislocalisation in motor neurons and neuromuscular defects in vivo.
Journal article
Williamson MG. et al, (2019), Hum Mol Genet, 28, 3584 - 3599
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The interactome of human TDP-43 in a cellular model of amyotrophic lateral sclerosis
Conference paper
Feneberg E. et al, (2019), EUROPEAN JOURNAL OF NEUROLOGY, 26, 221 - 222
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Single-copy expression of an amyotrophic lateral sclerosis-linked TDP-43 mutation (M337V) in BAC transgenic mice leads to altered stress granule dynamics and progressive motor dysfunction.
Journal article
Gordon D. et al, (2019), Neurobiol Dis, 121, 148 - 162
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Absence of wide-spread mis-splicing in the preclinical phase of a native promoter driven TDP-43 mouse model of ALS
Conference paper
Scaber J. et al, (2016), EUROPEAN JOURNAL OF NEUROLOGY, 23, 797 - 797