Professor Sherif El-Khamisy

Department of Molecular Biology and Biotechnology

Chair in Molecular Medicine

Deputy Director of the Healthy Lifespan Institute

Chair in Molecular Medicine, Sherif El-Khamisy
S.El-Khamisy@sheffield.ac.uk
+44 114 222 2791

Full contact details

Professor Sherif El-Khamisy
Department of Molecular Biology and Biotechnology
Firth Court
Western Bank
Sheffield
S10 2TN
Profile

Career history

  • 2015 - present: Director of Research and Innovation
  • 2014 - present: Chair of Molecular Medicine, Krebs Institute, University of Sheffield
  • 2014 - present: Wellcome Trust Investigator, Krebs Institute, University of Sheffield
  • 2014 - present: Lister Research Fellow, Krebs Institute, University of Sheffield
  • 2013 - 2015: Wellcome Trust Group Leader, Genome Center, University of Sussex
  • 2013 - 2014: Reader, Krebs Institute, University of Sheffield
  • 2008 - 2013: Wellcome Trust Fellow, Genome Center, University of Sussex
  • 2007 - 2008: MRC Post-doctoral Fellow, Genome Center, University of Sussex, UK
  • 2006: Post-doctoral Fellow, Dept. of Genetics, St Jude Children’s Research Hospital, USA
  • 2005: Lecturer, Dept. of Biochemistry, Ain Shams University, Egypt
  • 2002 - 2005: PhD in Biochemistry, University of Sussex, UK

Video animations summarising recent research discoveries

This video describes how DNA repair guards us against ALS, in particular the most common genetic cause for ALS and frontotemporal dementia caused by expansion in a gene called C9orf72. It summarises the work published in Nature Neuroscience on 17 July 2017.

How can the cells' powerhouse - mitochondria - protect their DNA? This video summarises a recent publication in Science Advances.


Major scientific accomplishments

  • Discovery of the mechanism of genomic instability and neural cell death in C9orf72 ALS (Nature Neuroscience 2017)
  • Discovery of protein-linked chromosomal break repair in the mitochondria (Science Advances 2017)
  • Discovery of a novel therapeutic strategy for ALS by inhibiting nuclear export (Nature communications 2017)
  • Elucidation of an epigenetic mechanism underlying irinotecan resistance in colorectal cancer (Nucleic Acids Research 2016)
  • Development of a nano-genomic technology to diagnose nucleic acid based infections (Biosensors 2016)
  • Discovery of the first human diseases resulting from accumulation of Top2-linked DNA breaks (Nature Genetics 2014)
  • Elucidation of the mechanisms underlying temozolomide therapy in brain tumors (Nucleic Acids Research 2014)
  • Development of techniques to measure protein-linked chromosomal breaks (Plos One 2013)
  • Identification of the molecular role of SUMOylation during single-strand break repair (Nature Communications 2012)
  • Identification of the role of XRCC1 during neural development and maintenance (Nature Neuroscience 2010)
  • Discovery of the enzyme that disjoins abortive topoisomerase 2 DNA breaks (Nature 2009)
  • Discovery of the function of the neuroprotective enzyme aprataxin (Nature 2006)
  • Identification of the first human disease with defects in chromosomal single-strand break repair (Nature 2005)
  • Elucidation of the role of CK2 in chromosomal single-strand break repair (Cell 2003)
Qualifications

Honours and distinctions

  • Wellcome Trust Investigator Award
  • Fellow of the Royal Society of Chemistry
  • Fellow of the Royal Society of Biology
  • Fellow of the Lister Institute of Preventative Medicine
  • Shoman Award for Medical Sciences
  • Sir Richard Stapley Award, UK
  • Lorne Duncan Award, UK
Research interests

The intertwined nature of the DNA double helix creates topological barriers that need to be resolved during all types of DNA transactions, in all forms of life from plant to man.

DNA topoisomerases achieve this by breaking and sealing the double helix, allowing the DNA to become untangled or unwound. During their normal catalytic cycle DNA topoisomerases become covalently attached to the DNA 3’-end (Top1) or to the 5’-end (Top2) via a reversible covalent phosphotyrosyl bond.

The presence of nearby oxidative DNA breaks (red circles) or collision with elongating RNA polymerases (RNA POL) during transcription results in ‘trapping’ of topoisomerases on DNA, causing protein-linked DNA breaks (PDBs), which are potent blocks to transcription and cell viability.

PDBs are repaired by a nucleolytic cleavage of DNA releasing the stalled Top and a fragment of DNA. Since this process results in an inevitable loss of genetic material, it is inherently error-prone.

Alternatively, PDBs can be repaired by an error-free mechanism in which the covalent phosphotyrosyl bond linking DNA to the stalled Top is cleaved by specific enzymes, such as tyrosyl DNA phosphodiesterases (TDP1 and TDP2). Interestingly, defects in TDPs cause neurological disease in man (see Fig.2).

In addition to maintaining genetic integrity in post-mitotic non cycling cells, accumulation of PDBs in cycling cells has been widely exploited to treat cancer (e.g. topoisomerase poisons such as Irinotecan and Topotecan), and therefore small molecule inhibitors of TDPs are emerging as attractive strategies to improve cancer therapy.

Publications

Show: Featured publications All publications

Journal articles

All publications

Journal articles

Chapters

Conference proceedings papers

  • Hegazy MT, Allam W, Hussein MA, Zoheir N, Quartuccio L, Cacoub P, Doss W, Ellawindi MI, Fawzy M, Guillevin L , El Ray A et al (2018) DNA Damage and Repair in Patients with Cryoglobulinemic Vasculitis Treated with Direct Anti-HCV Drugs. ARTHRITIS & RHEUMATOLOGY, Vol. 70 RIS download Bibtex download
  • Hassan M, Mohamed Z, Okasha S, Watari H & EL-Khamisy S (2017) COMPARATIVE MIRNA MICROARRAY PROFILING INDICATES MIR-363 PROMOTES CHEMORESISTANCE IN OVARIAN CANCER CELLS BY TARGETING THE HIPPO MEMBER, LATS2. INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol. 27 (pp 1952-1952) RIS download Bibtex download
  • Sakuragi N, Farah MK, Mohamed Z, Okasha S, Watari H, Mitamura T, Khamisy SE & Ohba Y (2017) Abstract LB-323: Comparative miRNA microarray profiling indicates miR-363 promotes chemoresistance in ovarian cancer cells by targeting the Hippo member, LATS2. Molecular and Cellular Biology, Genetics RIS download Bibtex download
  • Hegazy MT, Hussein MA, Quartuccio L, Fawzy M, Zoheir N, Ellawindi MI, Bond M, Mazzaro C, El Ray A, El Raziky MES , El Serafy M et al (2016) Treatment of Cryoglobulinemic Vasculitis with Sofosbuvir in Four Combination Protocols. ARTHRITIS & RHEUMATOLOGY, Vol. 68 RIS download Bibtex download
  • Lebedeva N, Rechkunova N, El-Khamisy S & Lavrik O (2013) Tyrosyl-DNA phosphodiesterase 1-a new player in base excision repair. FEBS JOURNAL, Vol. 280 (pp 63-64) RIS download Bibtex download
Research group

I welcome applications from self-funded prospective home and international PhD students; see examples of possible projects below.

You can apply for a PhD position in MBB here.

Contact me at S.El-Khamisy@sheffield.ac.uk for further information.

Teaching activities

Level 3 Modules

MBB313 Genome Stability and Genetic Change

Level 2 Modules

MBB262 Genetics 2