My research focuses on kinase biology and how kinase signalling pathways are hijacked in cancer. We combine computational biology with proteomics and cell biology to uncover novel ways to target these dysregulated networks.
The Aurora B specificity switch is required to protect from non-disjunction at the metaphase/anaphase transition. Nature Communications (2020) 11(1):1396–14. PMID: 32170202
PKCε Controls Mitotic Progression by Regulating Centrosome Migration and Mitotic Spindle Assembly. Molecular Cancer Research (2018) 16(1):3-15. PMID: 29021232
PKCɛ switches Aurora B specificity to exit the abscission checkpoint. Nature Communications (2016) ;7:13853. PMID: 28004745
Mitotic catenation is monitored and resolved by a PKCε-regulated pathway. Nature Communications (2014); 5(1):5685. PMID: 25483024
Kinases are attractive therapeutic targets for cancer. Approximately 25% of the known 535 kinases are associated with cancer through mutation, overexpression or aberrant signalling. However, the majority of therapies targeting kinases in cancer patients fail, due to development of resistance, or toxicity. We are working to develop new approaches to target cancer kinases to overcome these limitations.
We have described a novel mechanism by which kinase substrate specificity is regulated. Modification of the kinase activation loop by phosphorylation or mutation can alter substrate specificity. In cancer, this can lead to the rewiring of signalling pathways to promote oncogenic properties. How substrate specificity is determined, particularly relating to activation-loop modification is a hitherto unexplored niche which will provide new insights in the targeting of kinases in cancer.
This now provides an exciting opportunity to significantly advance understanding of the fundamental biology of kinase regulation. These new insights will enable the discovery of previously unknown or undefined signalling nodes and establish a route to developing new kinase inhibitors for personalised cancer therapy through the delivery of a high-resolution understanding of kinase regulation and dysregulation in cancer.
Genome-Protective Topoisomerase 2a-Dependent G
Co-ordinated control of the Aurora B abscission checkpoint by PKCϵ complex assembly, midbody recruitment and retention Watson L, Soliman TN, Davis K et al. Biochemical Journal (2021) 478(7) 2247-2263
A cancer-associated, genome protective programme engaging PKCε Parker PJ, Lockwood N, Davis K et al. Advances in Biological Regulation (2020) 78(7)
Author Correction: The Aurora B specificity switch is required to protect from non-disjunction at the metaphase/anaphase transition (Nature Communications, (2020), 11, 1, (1396), 10.1038/s41467-020-15163-6) Kelly JR, Martini S, Brownlow N et al. Nature Communications (2020) 11(1)
The Aurora B specificity switch is required to protect from non-disjunction at the metaphase/anaphase transition Kelly JR, Martini S, Brownlow N et al. Nature Communications (2020) 11(7)
Equivocal, explicit and emergent actions of PKC isoforms in cancer Parker PJ, Brown SJ, Calleja V et al. Nature Reviews Cancer (1)
Specific mechanisms of chromosomal instability indicate therapeutic sensitivities in high-grade serous ovarian carcinoma. Mcclelland S, Tamura N, Shaikh N et al. Cancer Research (2020) (1)
A genome-wide RNAi screen identifies the SMC5/6 complex as a non-redundant regulator of a Topo2a-dependent G2 arrest Deiss K, Lockwood N, Howell M et al. Nucleic Acids Research (2019) 47(7) 2906-2921
Inhibitor-induced HER2-HER3 heterodimerisation promotes proliferation through a novel dimer interface Claus J, Patel G, Autore F et al. eLife (2018) 7(7)
PKCϵ controls mitotic progression by regulating centrosome migration and mitotic spindle assembly Martini S, Soliman T, Gobbi G et al. Molecular Cancer Research (2018) 16(7) 3-15For additional publications, please click here
I completed my Bachelor of Science at the University of Queensland, Australia, before going on to an Honours program at the Queensland Institute for Medical Research. I attained my PhD from the University of Queensland, studying the role of MAP kinase signalling in the cell cycle and mitosis with Professor Brian Gabrielli.
After completing my PhD, I moved to London to start a Postdoctoral Fellowship with Professor Peter Parker initially at the CRUK London Research Institute, Lincolns Inn Fields and then moving to the Francis Crick Institute when it opened in 2015. Here I investigated the genome protective role of the kinase PKCε, in the cell cycle.
In 2019, I commenced a postdoc with Dr Sarah McClelland here at Barts Cancer Institute, researching chromosomal instability in High Grade Serous Ovarian Cancer and started my own independent laboratory at BCI in July 2020.