Professor Sherif El-Khamisy

Research

I am a pharmacist interested in understanding how cells maintain genomic integrity. I use interdisciplinary approach fusing genetics, cell biology, biochemistry and spectroscopy with clinical expertise. To further strengthen our translational agenda, I recently took up a joint appointment between the University of Sheffield and the University of Bradford to head the Institute of Cancer Therapeutics. My contributions led to discovery of novel genetic pathways, influenced healthcare practice and developed new technologies. My early work demonstrated a role for PARP1 and CK2 during chromosomal single-strand break (SSB) repair (NAR 2003, Cell 2004). I then moved into more translational aspects, which led to the identification, for the first time, of a defect in SSB repair in two human disorders (Nature 2005 and 2006). Following training at St Jude Hospital in the US, I employed mice to demonstrate the importance of SSB repair for organismal function (EMBO J 2007 and Nature Neuroscience 2009). My interest in this area led to a search for novel activities that repair topoisomerase-linked DNA breaks and resulted in the discovery of the enzyme that repairs topoisomerase 2 - mediated DNA damage, TDP2 (Nature 2009). This seminal finding is critical for a broad range of human disease including cancer. I demonstrated that topoisomerase-induced DNA breaks are pathogenic in other disorders (Hum Mol Gent 2010, Nature Genetics 2014, Nature Neuroscience 2017) and identified key posttranslational modifications and functions (Nature Communications 2012, NAR 2012 & 2016 and Cell Reports 2018). I reviewed the importance of topoisomerase-mediated DNA repair (Nature Rev Cancer 2015, Brain 2018) and described how it maintains mitochondrial gene transcription (Science Advances 2017). We uncovered a novel mechanism by which typhoid toxin exhausts the DNA repair machinery (Nature Communications 2019) and identified TEX264 as a novel component of the topoisomerase-mediated DNA repair pathway (Nature Communications 2020).