Protein function and activity must be tightly controlled. A major way in which this is achieved is via the addition/removal of post-translational modifications, including the methylation of arginine residues by PRMTs. Although arginine methylation was discovered more than 40 years ago, compared to other protein modifications such as phosphorylation, acetylation and ubiquitylation, we still know relatively little about the substrate repertoire of PRMTs, or the mechanism by which arginine methylation regulates cellular events.
These are important questions because PRMT activity and expression is upregulated in cancer, hence PRMTs, or their methylated substrates, represent novel drug targets. Understanding which proteins are methylated by PRMT in cancer and how this contributes to disease is the main focus of our lab. Additionally, this knowledge could provide us with biomarkers in which to determine which patients may respond to PRMT inhibitors that are now in clinical trials.
Our approach is to use molecular, biochemical and cell biology approaches, coupled with proteomic and genomic analysis, and in vivo mouse models of human cancers, to fully address the complexity of arginine methylation.
Have a look at some of the projects we are working on below: