Dr Will Brackenbury
Lecturer in Biomedical Sciences

Profile

Career

2016 - Lecturer in Biomedical Sciences Department of Biology, University of York
2011 - 2016 MRC Career Development Fellow Department of Biology, University of York
2009 - 2010 Adjunct Lecturer University of Michigan
2006-2010

Post-doc

University of Michigan Medical School
2006 PhD Biological Sciences Imperial College London
2002 BSc Biology Imperial College London

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.

Projects

Regulation of cancer cell migration by voltage-gated sodium channels

Research group(s)

 StatusNameProject
PhD student Alexander Haworth Proteolytic processing of sodium channel beta-1 subunits (joint with Dr. Christoph Baumann and Prof. Bob White)
Postdoc Ming Yang Intravital multiphoton imaging of the brain: integrating immunology, neuroscience and cancer biology
PhD student Faheem Patel

Targeting cell adhesion using aptamers

Senior Technician Michaela Nelson Regulation of cancer cell migration by sodium channels

Available PhD research projects

Breast cancer electrophysiology: Understanding the function of sodium channels in tumours (2016-2017)

Voltage-gated Na+ channels (VGSCs) contain pore-forming alpha subunits and smaller beta subunits. The beta subunits are multifunctional channel modulators and cell adhesion molecules. VGSC alpha and beta subunits are classically known to regulate electrical excitability and migration during central nervous system development. VGSCs are up-regulated in breast cancers and promote tumour growth, invasion and metastasis. In addition, VGSCs contribute to the relatively depolarised membrane potential (Vm) that is characteristic of breast cancer cells, which may in turn regulate cellular proliferation and migration. We will test the hypothesis that VGSCs contribute to Vm depolarisation and that this in turn enables cells to migrate and invade out of the tumour. We will use tissue slices from a mouse tumour model to determine the relationship between VGSCs and Vm in tumour cells and understand how these features contribute to metastasis. Electrophysiological study of ion channel function in tissue slices is widely used by neuroscientists, but has not been applied to breast oncology, so this approach is highly novel. Using a combination of patch clamp recording, channel modulation, organotypic culture, and immunohistochemistry in tissue microarrays, we will investigate expression and involvement of VGSCs in regulating Vm and invasion. This work may uncover ion channels as novel therapeutic targets in oncology. Existing VGSC-modulating drugs, e.g. antiepileptics, may also be effective in breast cancer. There is no evidence that such drugs influence immune effector function and so they could be used to complement conventional chemotherapies and emerging immunotherapeutics.
 
Co-director: Dr. Mark Coles
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Contact details

Dr William Brackenbury
Lecturer in Biomedical Sciences
Room B/E111
Department of Biology, Area 5
University of York, Heslington, York, YO10 5DD, UK

Tel: +44 (0) 1904 328 284

https://sites.google.com/a/york.ac.uk/brackenbury-lab/home