We study the signalling mechanisms cells use to respond to DNA damage and why defects in these pathways cause human diseases such as cancer.

Blackford lab

Mutations caused by DNA damage enable a normal cell to become cancerous. This is highlighted by the fact that individuals with mutations in many genes involved in DNA damage recognition, signalling and repair are predisposed to cancer, and that somatically acquired defects in such genes can drive tumour formation. Furthermore, some of the most effective cancer treatments work in tumour cells by inducing DNA damage, particularly DNA double-strand breaks, which are especially toxic and difficult to repair accurately without introducing mutations. Exploiting knowledge of DNA double-strand break repair is therefore likely to lead to more effective and personalised cancer therapies and treatments for patients with DNA repair disorders in future.

The aim of our research is to gain a greater understanding of the signalling mechanisms cells use to coordinate DNA double-strand break recognition and repair with cell cycle checkpoint activation and apoptosis. To achieve this, we are using cutting-edge bioinformatics, proteomics, microscopy and CRISPR-Cas9 gene-editing techniques to answer specific questions related to DNA damage signalling. In doing so, we hope to provide novel insights into carcinogenesis and how it is held at bay by the cell’s DNA damage response system. We also aim to translate our research to develop novel potential cancer treatments. In particular, we are interested in the potential utility of signalling events for use as biomarkers and to identify novel targets in the DNA damage response for anti-cancer drugs.

A major focus of our work is trying to understand how the products of genes mutated in DNA repair and cancer predisposition disorders such as Bloom syndrome are regulated by post-translational modifications and protein-protein interactions. Patients with Bloom syndrome suffer from a variety of symptoms including growth retardation, immunodeficiency, hypersensitivity to sunlight in addition to cancer predisposition. It is caused by mutations in BLM, a DNA helicase that plays important roles in coordinating DNA double-strand break repair and recombination, particularly during DNA replication and mitosis. However, we still know little about how this protein is regulated during the repair process and throughout the cell cycle. We are addressing this question by characterising novel post-translational modifications and protein-protein interactions of BLM and its binding partners.

Our team

Selected publications


Sofiya Levytska, Erasmus Student (2017)
Sofiya has returned to Italy to complete her Masters degree at the University of l’Aquila.

Emily Graham, Wellcome Trust Summer Student (2017)
Emily left us to complete her final undergraduate year at the University of Birmingham.