I studied Medicine at the University of Birmingham (1991-97) and continued my general medical training in Oxford. I then spent three years working on the genetic linkage and association of neurological disorders under the supervision of Professor George Ebers at the Wellcome Trust Centre for Human Genetics. After obtaining my DPhil in 2003, I completed my training in Clinical Neurology at Oxford. I joined the Department of Physiology, Anatomy and Genetics in 2007 after being awarded an MRC Clinician Scientist Fellowship to establish my own research group.
I am now the Academic Director and Principial Scientist for IMI StemBANCC. I am also active clinically and work as a Consultant Neurologist at the John Radcliffe Hospital with an interest in Neurogenetic and Headache Disorders. I am Director of the Oxford Headache Centre.
Director of the Oxford Headache Centre and Director of StemBANCC
- Associate Professor
- Clinical Director, Thames Valley Strategic Clinical Network
- Consultant Neurologist
Molecular disease mechanisms and cellular disease phenotypes in neurological disorders
The Translational Molecular Neuroscience Group looks at neurogenetic disorders, often rare variants of common disease. Understanding the disease pathways in these conditions will allow development of meaningful therapies. The group is developing new disease models for more effective drug discovery platforms.
The Neurobiology of Migraine
The other major area of research for the group is understanding pathogenic mechanism in migraine. Migraine is a common, costly and debilitating condition with a complex genetic aetiology. The genetics basis of typical migraine is mostly unknown but we have identified the first gene underlying typical migraine. We found in a large family with migraine, a frameshift mutation in the gene KCNK18, which encodes a tandem-pore background potassium channel, TRESK. TRESK is highly expressed in dorsal root, trigeminal and autonomic ganglia and to lesser extents in the brain and spinal cord. In vitro electrophysiology demonstrates the mutation, which produces a prematurely truncated protein, causing complete loss of function when expressed alone and a dominant negative effect when expressed with wildtype channels. We believe that loss of TRESK function increases cell excitability and responsiveness and thereby lowers the threshold for migraine development. We are building on these findings to further our understanding of migraine and develop new drug treatments.
Sources of Funding
- EU FP7
- Wellcome Trust
- NIHR BRC
- Medical Research Council
- John Fell
Targeted single-cell RNA sequencing of transcription factors enhances the identification of cell types and trajectories.
Pokhilko A. et al, (2021), Genome Res
Global proteomic analysis of extracellular matrix in mouse and human brain highlights relevance to cerebrovascular disease.
Pokhilko A. et al, (2021), J Cereb Blood Flow Metab
TRESK is a key regulator of nocturnal suprachiasmatic nucleus dynamics and light adaptive responses.
Lalic T. et al, (2020), Nat Commun, 11
Targeted RNA sequencing enhances gene expression profiling of ultra-low input samples
CADER M. et al, (2020), RNA Biology
Patient fibroblast circadian rhythms predict lithium sensitivity in bipolar disorder.
Sanghani HR. et al, (2020), Mol Psychiatry