Profile

Career

Research

Overview

Voltage-gated sodium channels are responsible for the initiation and propagation of action potentials, and are therapeutic targets in excitability-related disorders including cardiac arrhythmias, pain and epilepsy. They also play an important role in regulating neuronal pathfinding and migration during brain development. I am interested in the novel role of sodium channels in regulating the migration and invasion of metastatic cancer cells. This requires understanding the mechanisms by which sodium channels regulate adhesion and migration, during nervous system development on the one hand, and cancer metastasis on the other. An important focus of research in my lab is to extend in vitro observations from cell lines towards the clinic, developing in vivo models and human tissue sample analyses.

Two references

• Brackenbury WJ. (2012). Voltage-gated sodium channels and metastatic disease. Channels (Austin).
• Yang Y, Kozminski DJ, Wold LA, Modak R, Calhoun JD, Isom LL and Brackenbury WJ. (2012). Therapeutic potential for phenytoin: targeting Nav1.5 sodium channels to reduce migration and invasion in metastatic breast cancer. Breast Cancer Res. Treat. 134, 603-615.

Discoveries

Voltage-gated sodium channels function as macromolecular protein complexes in which both pore-forming α subunits and smaller non-pore-forming β subunits interact with other signalling molecules. We have shown that α and β subunits function in concert within these complexes in neurons to jointly regulate electrical excitability, neurite outgrowth, migration and organogenesis.

Current projects

Regulation of cancer cell migration by voltage-gated sodium channels
Funding body: MRC

Research group(s)

Publications

Selected publications

Brackenbury WJ, Yuan Y, O'Malley HA, Parent JM and Isom LL. (2012). Abnormal neuronal patterning occurs during early postnatal brain development of Scn1b-null mice and precedes hyperexcitability. Proc. Natl. Acad. Sci. USA. DOI: 10.1073/pnas.1208767110.

Brackenbury WJ. (2012). Voltage-gated sodium channels and metastatic disease. Channels (Austin) 6 (5).

Yang Y, Kozminski DJ, Wold LA, Modak R, Calhoun JD, Isom LL and Brackenbury WJ. (2012). Therapeutic potential for phenytoin: targeting Nav1.5 sodium channels to reduce migration and invasion in metastatic breast cancer. Breast Cancer Res. Treat. 134, 603-615.

Brackenbury WJ and Isom LL (2011). Na+ Channel β Subunits: Overachievers of the Ion Channel Family. Front. Pharmacol. 2, 53.

Patino GA, Brackenbury WJ, Bao Y, Lopez-Santiago LF, O'Malley HA, Chen C, Calhoun JD, Lafrenière RG, Cossette P, Rouleau GA and Isom LL. (2011). Voltage-gated Na+ channel β1B: a secreted cell adhesion molecule involved in human epilepsy. J Neurosci. 31, 14577-91.

Lopez-Santiago LF, Brackenbury WJ, Chen C and Isom LL. (2011). Na+ channel Scn1b gene regulates dorsal root ganglion nociceptor excitability in vivo. J. Biol. Chem. 286, 22913-23.

Brackenbury WJ, Calhoun JD, Chen C, Miyazaki H, Nukina N, Oyama F, Ranscht B and Isom LL. (2010). Functional reciprocity between Na+ channel Nav1.6 and Beta1 subunits in the coordinated regulation of excitability and neurite outgrowth. Proc. Natl. Acad. Sci. USA. 107, 2283-2288.

Chioni A-M, Brackenbury WJ, Isom LL and Djamgoz MB. (2009). A novel cell adhesion molecule in human breast cancer cells: Voltage-gated Na+ channel Beta1 subunit. Int. J. Biochem. Cell Biol. 41, 1216-27.

Brackenbury WJ, Djamgoz MB and Isom LL. (2008). An emerging role for voltage-gated Na+ channels in cellular migration: Regulation of central nervous system development and potentiation of invasive cancers. The Neuroscientist. 14, 571-583.

Brackenbury WJ, Davis TH, Chen C, Slat EA, Detrow MJ, Dickendesher TL, Ranscht B and Isom LL. (2008). Voltage-gated sodium channel Beta1 subunit-mediated neurite outgrowth requires fyn kinase and contributes to central nervous system development in vivo. J. Neurosci. 28, 3246-3256.

External activities

Memberships

Member of the British Association for Cancer Research
Member of the European Association for Cancer Research
Member of the Physiological Society
Member of the American Association for Cancer Research