The main focus of my lab’s research is investigating whether signalling by the small GTPase RAC1 could be a good therapeutic target in lung cancer and specifically in KRAS-mutant lung adenocarcinoma (KRASm-LUAD) and small cell lung cancer (SCLC). KRASm-LUAD and SCLC are major causes of morbidity and mortality, reflecting significant unmet clinical needs. RAC1 is required for KRASm-LUAD development and controls migration and invasion, cardinal features of malignant progression. However, RAC1 performs essential physiological roles and can antagonise tumour progression dependent on context: while generally promoting migration and invasion, RAC1-signalling can also do the opposite. Selectively targeting RAC1’s cancer-promoting effects is therefore critical to harnessing its full therapeutic potential. Interestingly, our research has highlighted that guanine nucleotide exchange factors (GEFs) stimulate RAC1 activity but also coordinate downstream effectors providing selectivity in RAC1-signalling. We are, therefore, currently evaluating the contribution of RAC1-GEF-signalling to KRASm-LUAD development and progression, and whether inhibiting RAC1-GEF signalling can sensitise KRASm-LUADs to KRAS inhibitors that have recently entered the clinic. We are also evaluating the role of RAC1-GEF-signalling in the development, plasticity and metastasis of SCLC.

In another project of my lab, in close collaboration with my main clinical collaborator Dr Colin Lindsay, we are looking into differences in signalling emanating from two different KRAS G12 mutations. This follows on from exciting in vivo and in vitro data from our lab that oncopotency and signalling downstream from two different KRAS G12 mutations can be diverse. We are also investigating mechanisms of resistance to KRAS inhibitors that have recently entered the clinic using either cell models or patient samples from the Christie Hospital, a major UK cancer hospital based in Manchester.

PhD opportunities

Projects are now available within our team for motivated PhD candidates  to work on SCLC plasticity, invasion and metastasis:

SCLC invasion and metastasis (CRUK funded non-clinical)

SCLC plasticity (self-funded)

and KRAS-mutant NSCLC invasion:

NSCLC invasion (MRC DTP funded)

Follow the links for more information about the projects and how to apply.