Sheffield Institute for Nucleic Acids

Professor Sherif El-Khamisy

Research Interests

Professor El-Khamisy is a pharmacist by training and currently holds a Wellcome Trust investigator,  studying the mechanisms underpinning human disorders arising from defective DNA repair.  His work led to the conceptual hypothesis that fixing single-strand breaks, the most abundant form of endogenous DNA breakage, is critical for the genetic integrity in post-mitotic tissue. He and his group also study how cancer cells respond to therapies that cause DNA breaks such as chemotherapy and radiotherapy, with the view to develop new strategies for diagnosis and treatment.

Professor El-Khamisy’s specific aim is to address the impact of oxidative and protein-linked DNA breaks on pathological and age-associated organ dysfunction. His group use a combined biochemical and genetic approach coupled with the utilisation of yeast, mouse and zebrafish as model organisms.


Publications

  • Meisenberg C, Gilbert DC, Chalmers A, Haley V, Gollins S, Ward SE, El-Khamisy SF (2015). Clinical and cellular roles for TDP1 and TOP1 in modulating colorectal cancer response to irinotecan. Mol Cancer Ther. 14(2): 575-85
  • Carroll J, Page TK, Chiang SC, Kalmar B, Bode D, Greensmith L, Mckinnon PJ, Thorpe JR, Hafezparast M, El-Khamisy SF (2015). Expression of a pathogenic mutation of SOD1 sensitizes aprataxin-deficient cells and mice to oxidative stress and triggers hallmarks of premature ageing. Hum Mol Genet. 24(3): 828-40 [The first to show a neuroprotective role of aprataxin in a mouse model]
  • Ashour ME, Atteya R, El-Khamisy SF (2015). Topoisomerase-mediated chromosomal break repair: an emerging player in many games. Nat Rev Cancer. 15(3): 137-51
  • Gómez-Herreros F, Schuurs-Hoeijmakers JH, McCormack M, Greally MT, Rulten S, Romero-Granados R, Counihan TJ, Chaila E, Conroy J, Ennis S, Delanty N, Cortés-Ledesma F, de Brouwer AP, Cavalleri GL, El-Khamisy SF*, de Vries BB*, Caldecott KW* (2014). TDP2 protects transcription from abortive topoisomerase activity and is required for normal neural function. Nat Genet. 46: 516–52 *Corresponding author [identifies the first human disease with defects in TDP2 with concomitant accumulation of protein-linked DNA breaks (PDBs) during transcription]
  • Alagoz M, Wells OS, El-Khamisy SF (2014). TDP1 deficiency sensitizes human cells to base damage via distinct topoisomerase I and PARP mechanisms with potential applications for cancer therapy. Nucleic Acids Res 1; 42(5): 3089-103.
  • Zeng, Z., Sharma, A., Murai, J., Pommier, Y., Takeda, S., Huylebroeck, D., Caldecott, K., El-Khamisy, SF (2012). TDP2 Promotes Repair of Topoisomerase 1-mediated DNA damage in the absence of TDP1. Nucleic Acids Res, 40(17): 8371-80
  • Hudson, J.R., Chiang, S., Wells, O.S., Rookyard, C., El-Khamisy, SF (2012). SUMO modification of the neuroprotective protein TDP1 facilitates chromosomal single-strand break repair. Nature Commun, 13; 3:733 [the first to show a role for SUMO modification of a single-strand break repair protein and illustrates its importance during the repair of transcription-blocking DNA breaks]
  • Cortes-Ledesma F.*, El-Khamisy, SF *, Zuma, M., Osbourne, K., Caldecott, K.W. (2009). Identification of a Human 5’-Tyrosyl DNA Phosphodiesterase That Repairs Topoisomerase- Mediated DNA Damage. Nature, 461(7264):674-8 * Equal contributions. [Discovery of the PDB repair factor TDP2]
  • Lee, Y., Katyal, S., Li, Y., Russell, H.R., El-Khamisy, S.F., Caldecott, K.W., Mckinnon, P.J. (2009). Genesis of cerebellar interneurons and the prevention of neural DNA damage require XRCC1. Nature Neuroscience. 12(8):973-80. [The first report of the importance of XRCC1 in the nervous system]
  • Katyal, S.*, El-Khamisy, SF*, Russel, H.R., Li, Y., Ju, L., Caldecott, K.W., McKinnon, P.J. (2007). TDP1 facilitates chromosomal single-strand break repair in neurons and is neuroprotective in vivo. EMBO J, 14; 26(22):4720-31. * Equal contributions. [Identification of the importance of SSB repair in neurons]
  • Ahe,l I., Rass, U., El-Khamisy, SF, Katyal, S., Clements, P.M., McKinnon, P.J., Caldecott, K.W., West, S.C (2006). The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates. Nature, 443, 713-6. [Discovery of the enzymatic activity of aprataxin]
  • El-Khamisy, SF, Saifi, G.M., Weinfeld, M., Johansson, F., Helleday, T., Lupski,J.R., and Caldecott, K.W. (2005) Defective DNA Single-Strand Break Repair in Spinocerebellar Ataxia with Axonal Neuropathy-1. Nature, 434, 108-113. [Discovery of the first DNA single-strand break repair defect in a human disease]
Professor Sherif El-Khamisy
Professor of Molecular Medicine, Centre Scientific Meeting Co-ordinator
Department of Molecular Biology and Biotechnology
+44 (0)114 222 2791
s.el-khamisy@sheffield.ac.uk