Research groups
RESEARCH THEMES
Genome Integrity & Epigenetics
Radiation-Immune Interactions (Co-Investigator)
Student Project:
Nucleases and helicases as potential cancer targets
It is clear that the acquired genetic changes (vulnerabilities) in tumours can be exploited to treat cancer, increasingly in a manner tailored to individual patients. Defects and alterations in DNA repair pathways are often vital for tumour cell viability and are excellent potential therapeutic targets.
We combine cell biology, cellular genetics (including genome editing) and biochemistry (including cryo-electron microscopy) to provide a detailed understanding of key DNA repair pathways that are targets for cancer prevention and treatment.
COLLABORATORS
Prof Chris Schofield, Department of Chemistry, University of Oxford
Prof Tom Brown, Department of Chemistry, University of Oxford
Dr Joe Newman, Centre for Medicines Discovery, University of Oxford
Dr Andre Nussenzweig, National Cancer Institute, NIH, Bethesda, USA
Colleges
Peter McHugh
Professor of Molecular Oncology
Research Summary
We aim to understand how repair of damaged DNA is controlled during chromosome duplication, and why potentially dangerous changes in the behaviour of cells can occur when this process goes wrong. We also hope use this improved knowledge of DNA damage and its repair to improve treatments for cancer.
Biography
Following post-doctoral research at University College London, Peter McHugh was awarded a Royal Society University Research Fellowship in 2001. In 2003 he joined the Oncology Laboratories at the MRC Weatherall Institute of Molecular Medicine, where he now heads the DNA Damage and Repair research group.
He is a regular presenter to CRUK fundraisers, and is a co-organiser of the UK Genome Stability Network Annual meeting and of the FEBS Nucleotide Excision Repair and Interstrand Crosslink repair meeting.
GROUP MEMBERS
Katherine Ferris, DPhil student
William Foster, Postdoctoral researcher
Paul Guy, DPhil student
Grid Horsley, DPhil student
Iulia Kis, DPhil Student
Louise Martin, DPhil Student
Rebecca Roddan, Postdoctoral researcher
Lonnie Swift, Postdoctoral Researcher
Recent publications
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Transcription-coupled repair of crosslinking DNA damage.
Journal article
Roddan R. et al, (2025), DNA Repair (Amst), 152
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The dual ubiquitin binding mode of SPRTN secures rapid spatiotemporal proteolysis of DNA-protein crosslinks.
Journal article
Song W. et al, (2025), Nucleic Acids Res, 53
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The dual ubiquitin binding mode of SPRTN secures rapid spatiotemporal proteolysis of DNA-protein crosslinks.
Preprint
Song W. et al, (2024)
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Molecular insights into the stimulation of SNM1A nuclease activity by CSB during interstrand crosslink processing.
Preprint
Roddan R. et al, (2024)
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SNM1A is crucial for efficient repair of complex DNA breaks in human cells.
Journal article
Swift LP. et al, (2024), Nat Commun, 15
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Cell-active small molecule inhibitors validate the SNM1A DNA repair nuclease as a cancer target.
Journal article
Bielinski M. et al, (2024), Chem Sci, 15, 8227 - 8241
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N-Acyloxymethyl-phthalimides deliver genotoxic formaldehyde to human cells.
Journal article
Emms VL. et al, (2023), Chem Sci, 14, 12498 - 12505
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WRN helicase and mismatch repair complexes independently and synergistically disrupt cruciform DNA structures.
Journal article
Mengoli V. et al, (2023), EMBO J, 42