Research Overview

Fig 1: Formation of UV-C-induced nuclear foci in human TRG cells expressing a tetracycline-inducible polymerase eta-GFP fusion protein. Fluorescence microscopy was carried out 6h after UV-C treatment.

Fig 2: Enhanced cell cycle arrest in DNA polymerase eta-deficient human XP30RO cells treated with cisplatin or oxaliplatin

Our research interests include the molecular basis of the response of human cells to DNA damaging agents, such as the carcinogen ultraviolet light, and platinum-based chemotherapeutic agents including cisplatin and oxaliplatin.

To elucidate the effects of damage on DNA replication arrest, and the activation of downstream damage signaling pathways, we have developed unique human cell lines to investigate the role of human POLH gene product, DNA polymerase eta, in the response to DNA damaging agents, and used small molecule protein kinase inhibitors to probe the role of PIKK-dependent protein phosphorylation in this response, focusing on phosphorylation of replication protein A (RPA). The status of the POLH gene has also been characterised in a cohort of skin cancer patients.

Ongoing research areas include the characterisation of DNA damage response pathways in human mesenchymal stem cells (hMSCs), in collaboration with the Regenerative Medicine Institute at NUI, Galway, and characterisation of responses to novel derivatives of the anti-cancer drug mitomycin C in normal and Fanconi anemia cell lines (in collaboration with Dr. F. Aldabbagh, School of Chemistry, NUI, Galway).