Matthew White

Matthew.white@kcl.ac.uk

MattWhiteKCL

Website

Research Interests

Our lab is interested in the role RNA-binding proteins play in the development and function of the nervous system. We begin by identifying rare variants that are linked to neurological diseases, including ALS-FTD and the dementias. By combining CRISPR/Cas9 gene editing and neuronal differentiation, we study how these variants alter RNA-binding protein function and ultimately modify disease risk. These findings feed into the development of novel drug screening assays to bridge the gap between mechanistic insight and early-stage drug development to correct disease-associated phenotypes.

Most significant discovery

A subset of mutations in the low complexity domain of the key ALS-FTD protein TDP-43 fundamentally alter its autoregulation, expression, and cause widespread transcriptomic instability (PMID:29556029). This work highlights how a single point mutation can alter an RNA binding protein’s function, cause far reaching transcriptomic modifications, and contribute to neurodegeneration.

Educational Interests

Top 4 Publications

White & Kim et al. 2018. TDP-43 gains function due to perturbed autoregulation in a Tardbp knock-in mouse model of ALS-FTD.Nature neuroscience,21(4), 552– 563

White et al. 2019. Sarm1 deletion suppresses TDP-43-linked motor neuron degeneration and cortical spine loss. Acta neuropathologica communications,7(1), 166

Kim & White et al. 2020. Coexistence of perseveration and apathy in the TDP-43Q331K knockin mouse model of ALSFTD. Translational Psychiatry, 10(377)

White & Sreedharan, 2016. Amyotrophic lateral sclerosis: recent genetic highlights. Curr opin Neurol, 29(5), 557-564

Methods / Expertise

• Gene editing iPSCs – tags, point mutants, transgenes
• Inducible neuron differentiation
• Molecular biology & transcriptomics
• Imaging