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Full NameProfessor Richard Kennedy
Department:CENTRE FOR CANCER RESEARCH AND CELL BIOLOGY
Organisation:Queen's University Belfast
- genetics, genomics and molecular biology
Immune checkpoint PD-L1 cGAS STING "DNA Repair"
The Kennedy lab was the first to describe how genomic instability in cancer activates the cGAS-STING pathway through accumulation of cytoplasmic DNA. This results in the release of cytokines that attract lymphocytes into tumours. The cGAS-STING pathway is now known to be important in the response to novel cancer therapeutics that use the immune system to fight cancer such as PD-L1 inhibitors. The lab continue to investigate the mechanisms that activate the cGAS-STING pathway and how these can be harnessed to enhance the immune response to cancer.
Although 20-30% of solid tumours overall have genomic instability and cGAS-STING activation that may sensitize them to immune checkpoint targeted therapies such as pembrolizumab or ipilimumab, the majority have minimal or no immune activation. We are therefore interested in identifying approaches to activating the cGAS-STING pathway in order to sensitize these tumours to immune checkpoint-targeted therapies. Recent publications in the virology field have suggested that STING may be regulated through the Ubiquitin-Proteasome system. We have therefore created a human E3 ligase and DUB siRNA library which can be used with a cGAS-STING pathway reporter cell line to identify novel drug targets to activate the pathway. Potential targets will fully characterised in further cell line models and the most promising will be taken forward into drug development in collaboration with Professor Tim Harrison (Medicinal Chemistry).