Protein kinases are frequently mutated or otherwise dysregulated in cancer and inhibitors of protein kinases such as imatinib and crizotinib are key therapeutic drugs. Our research aims to determine the structural mechanisms that underpin kinase regulation and to develop new kinase inhibitors as potential cancer therapeutics. We resolved the allosteric mechanism by which the non-catalytic, C-terminal domain (CTD) of NEK9 activates NEK7 (Haq, Nat. Comm. 2015) and showed that IRE1 is regulated through a similar mechanism (Joshi, Oncotarget 2015). We have assisted in the development of inhibitors of the protein kinases Aurora-A, NEK2 and IRE1 and have ongoing collaborations on several other targets.
