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El-Khamisy Lab

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DNA Repair to the Rescue

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Sherif's background

Sherif El-Khamisy is a pharmacist who has been studying how cells maintain genomic integrity and their impact on health for the past 20 years. His lab uses multidisciplinary approach fusing genetics, chemistry and biology with clinical expertise. The work led to discovery of novel genetic pathways, influenced healthcare practice and developed new technologies. His early work demonstrated a role for PARP1 and CK2 during chromosomal single-strand break repair (NAR 2003, Cell 2004). El-Khamisy then moved into more clinical aspects, which led to the identification, for the first time, of a defect in single-strand break repair in two human neurological disorders (Nature 2005 and 2006). Following training at St Jude Hospital in the US, he employed mice to demonstrate the importance of DNA repair for neurological function (EMBO J 2007 and Nature Neuroscience 2009). El-Khamisy's interest in this area led to a search for novel pathways and resulted in the discovery of the enzyme that repairs topoisomerase 2 - mediated DNA damage, TDP2 (Nature 2009). This seminal finding has broad implications in multiple disciplines including aging, neuroscience, infections and cancer.

The lab demonstrated that topoisomerase-linked DNA breaks are pathogenic in other neurological disorders (Hum Mol Gent 2010, Nature Genetics 2014, Nature Neuroscience 2017) and identified key post-translational modifications (Nature Communications 2012, NAR 2012 & 2016, Cell Reports 2018). The lab reviewed the importance of oxidative and topoisomerase mediated repair during transcription (Nature Rev Cancer 2015, Brain 2018) and identified the mechanism by which they maintain mitochondrial gene transcription (Science Advances 2017). With colleagues in Sheffield and Oxford, they uncovered a novel mechanism by which the typhoid toxin exhausts the DNA repair machinery (Nature Communications 2019), identified TEX264 as a novel topoisomerase-mediated DNA repair factor (Nature communications 2020), and revealed the role of nucleotides in maintaining stem cell genomic integrity (Stem Cell Rep 2020). The lab received drug discovery awards from AstraZeneca and CRUK. Fusing their expertise with clinicians and nanotechnology led to development of new technologies and influenced healthcare policies (publications in Biosensors 2017 and Ebiomedicine 2018).

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Nobel Laurette Dr Zewail

                        Nobel Prize 1999

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Sir Alex Markham

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