Investigating DDK-dependent regulation of stalled replication forks

DNA replication is the fundamental mechanism of genetic inheritance. In cancer cells, replication is corrupted and replication forks frequently stall and collapse causing DNA damage and copying errors that drive tumorigenesis. As a result, cancer cells are heavily dependent on the pathways that protect and repair stalled replication forks. Disrupting these mechanisms can be selectively toxic to cancer cells. A key player in the regulation of DNA replication and repair is DDK (Dbf4-dependent kinase also known as Cdc7). DDK is frequently overexpressed in cancer, but its role during DNA replication and the repair of stalled forks has not been well characterised. Our team is using chemical genetic approaches to selectively target DDK and gain valuable insights into its requirements and molecular targets.

Applying long-read sequencing technology to understand telomere repair and DNA replication

Our team is appling long-read DNA sequencing technology to dissect the spatial and temporal regulation of DNA replication and understand repair pathways at telomeres. By implementing long-read sequencing approaches in these research areas, we aim to advance our structural and functional understanding of the human genome.

Reversing the “Warburg effect”: Targeting metabolic reprogramming and DNA repair to enhance immunogenic cell death in melanoma

This project seeks to identify novel treatment strategies for melanomas that do not respond to conventional chemotherapy or immunotherapy treatments. We are investigating whether the metabolic reprograming in melanoma can be harnessed for long term eradication by the immune system.