Our research centres on voltage-gated sodium channels (VGSCs), and their role in regulating membrane electrical activity, adhesion, process extension and cellular migration. The current focus is on the novel role of VGSCs in regulating the migration and invasion of metastatic breast cancer cells.
Voltage-gated sodium channels
VGSCs contain a large pore-forming α subunit, together with smaller non-pore-forming β subunits. The β subunits are members of the immunoglobulin superfamily of cell adhesion molecules. In particular, the β1 subunit interacts with a number of other cell adhesion molecules and signalling intermediates. Thus, VGSCs function as macromolecular protein complexes in which both the α subunits and β subunits interact with other signalling molecules. VGSCs are responsible for the initiation and propagation of action potentials, and are therapeutic targets in excitability-related disorders including cardiac arrhythmias, pain and epilepsy.
Neuronal pathfinding and migration
VGSCs play an important role in regulating neuronal pathfinding and migration during brain development. β1 subunits regulate channel activity, cell-cell adhesion, neurite outgrowth, pathfinding and migration in the developing central nervous system. We have shown that α and β subunits function in concert within macromolecular complexes in neurons to jointly regulate electrical excitability, neurite outgrowth, migration and organogenesis. In particular, there is functional reciprocity between β1 and the Nav1.6 α subunit, such that β1-mediated neurite outgrowth requires Nav1.6, and Nav1.6-dependent action potential firing requires β1.
Metastatic cell behaviour
We are interested in the novel role of VGSCs in regulating the migration and invasion of metastatic cancer cells. VGSC α and β subunits are expressed in metastatic cells from a number of cancers. The Nav1.5 α subunit is expressed in metastatic breast cancer cells, where it enhances migration and invasion, and associates with poor prognosis in patients. Thus a novel role is emerging for VGSCs in regulating excitability and migration, on the one hand during postnatal CNS development, and on the other, during cancer cell metastasis. As a result, VGSCs may be promising targets for therapeutic intervention in metastatic disease.
I am a biomedical scientist with an interest in ion channels and cell signalling in diseases including neurological disorders and cancer. My teaching reflects these research interests.
I provide undergraduate lectures in stages 2 and 3, in areas covering neuroscience, pharmacology and cancer. I also lead a module on Molecular Basis of Disease which is part of the stand-alone MSc in Molecular Medicine. Throughout, my lectures reflect on and relate to various rapidly developing areas of biomedical science.
I offer tutorials to stage 1 and stage 2 undergraduate students on the topic of ion channels in health and disease. These typically follow a journal club format in which we cover the topic by studying primary research papers.
I run laboratory, data analysis and science communication projects for stage 3 and stage 4 undergraduate students as well as students on the stand-alone MSc in Molecular Medicine. The projects always relate closely to our ongoing research in the lab, focusing on ion channels and disease. Techniques include cell culture, biochemistry, microscopy and image analysis.