Email: s.el-khamisy@sheffield.ac.uk

Research profile and key clinical specialties

I am a Wellcome Trust investigator studying the mechanisms underpinning neuronal demise due defective DNA repair with the goal of developing novel disease modifying strategies.

We also harness this knowledge to develop new approaches to treat cancer since most chemo and radiotherapy kill cancer cells by inducing DNA damage.

We achieve these aims by using a combined biochemical and genetic approach coupled with the utilisation of yeast, mouse and Zebrafish as model organisms.

We developed particular interest in protein-linked DNA breaks since their progressive accumulation causes neuronal death and their acute accumulation has been widely utilised to treat cancer.

The lab identified mechanisms by which DNA breaks cause cerebellar and spinocerebellar ataxias (e.g. Nature 2005, Nature 2006, Hum Mol Genet 2010, EMBO Mol Med 2011, Science Advances 2017), mental retardation (Nature 2009, Nature Genetics 2014), motor neuron disease (e.g. Nature Neuroscience 20017) and how can we exploit this knowledge to treat cancer (Nucleic Acids Research 2014, 2017, Nature Rev Cancer 2015, Nature communications 2021).

Two key publications

• Jurga M, Abugable AA, Goldman ASH, El-Khamisy SF (2021).USP11 controls R-loops by regulating senataxin proteostasis. Nature Communications, 12: 5156

• Walker C, Herranz-Martin S, Karyka E, Liao C, Lewis K, Elsayed W, Lukashchuk V, Chiang S-C, Ray S, Mulcahy PJ, Jurga M, Tsagakis I, Iannitti T, Chandran J, Coldicott I, De Vos K, Hassan MK, Higginbottom A, ShawPJ, Hautbergue GM, Azzouz M, El-Khamisy SF. (2017). C9orf72 Expansion Disrupts ATM-mediated Chromosomal Break Repair. Nature Neuroscience, 45: 1159

Possible PhD projects

• Modulating DNA repair as a novel approach to combat neurological disease
• The role of transcription associated DNA repair in hormone-driven cancer

More information

• View my full research profile

Keywords: DNA, chemotherapy, radiotherapy, cerebellar, spinocerebellar, ataxias, Zebrafish, retardation, Sherif, El-Khamisy, Sheffield

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