Understanding signal modulation by the inhibitory immune checkpoints

When specialised white blood cells recognise the signatures of pathogens and cancer, proteins expressed on their surfaces instruct the immune system to clear the threat. Other inhibitory proteins expressed by these cells can override these instructions, however, to prevent over-reactions. Recent years have witnessed great excitement over the therapeutic potential of these inhibitory proteins: by blocking their activity, the immune system can be primed to attack cancer cells, whereas enhancing their effects allows unwanted immune responses, such as colitis, to be switched off. Despite this excitement, important questions remain over what makes the inhibitory proteins inhibitory and how their expression is regulated after they exert their inhibitory effects. 

Using advanced ‘gene-editing’ methods and new assays that I will develop, I will address these questions in ways that haven't been possible previously. 

A deeper understanding of how these inhibitory proteins work should allow us to build upon the recent, remarkable developments in immunotherapy.