Our aim is to elucidate the pathophysiological basis of human neurological disorders from genetic molecular networks to complex neural systems. We achieve this through development of relevant disease models that will then serve as novel and robust platforms for drug discovery.
The group’s research covers 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. We focus upon two major disorders: peripheral motor neuropathies and migraine.
…opening up possibilities for new treatments which could help millions of people worldwide...Sir John Savile, MRC Chief Executive
Our cellular models range from primary cell cultures to human induced pluripotent stem cell lines derived directly from patients. We seek to identify the molecular and cellular signatures of neurogenetic disorders using omics analysis, cellular imaging and electrophysiology. We aim to construct more relevant neuronal models through tissue engineering and 3D cell culture. We employ model organism such as the fly to validate hypotheses and findings from our in vitro systems. We are also undertaking human imaging studies, in collaboration with the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB)
Stem cell disease models
We are developing new in vitro human stem cell models to better understand disease biology and to develop assays for drug screening.
We have new and efficient protocols to generate neurovascular co-culture models comprising of brain microvascular endothelial cells, astrocytes and neurons. This models recapitulates the blood-brain-barrier with strong expression of brain specific tight junction markers.
We also have optimised protocols for generating cortical neurons and nociceptive neurons
Migraine is a common, costly and debilitating condition with a complex genetic aetiology. The genetic 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 in migraine salient regions such as the trigeminal ganglion. In vitro electrophysiology demonstrates the mutation, which produces a prematurely truncated protein, causes complete loss of function.
We believe that loss of TRESK function increases cell excitability and responsiveness and thereby lowers the threshold for migraine development. We are now exploring genetic modifiers in primary cell culture and human induced pluripotent stem cell derived neuronal cultures. We are also undertaking structural and fMRI in migraine patients to reveal neural pathways critical to migraine predisposition and triggering. We are building on these findings to further our understanding of migraine and develop new drug treatments.
Collaborators & Students
Current DPhil Students:
Jes Olesen, Danish Headache Center
David Bennett, NDCN
Quin Wills, WTCHG
Working in our group
- Get in touch if you would like to study for an MSc or DPhil with our group. We have projects in single cell transcriptomics, stem cell models, transgenics and brain imaging. You may already have funding or we can support applications for funding.
Professor Zameel Cader is a Consultant Neurologist at the John Radcliffe Hospital and is Director of the Oxford Headache Centre. He runs specialist clinics in neurogenetics and migraines. Please contact your GP if you would like to be seen on the NHS.
He also offer private neurology clinic appointments. Please ask your GP to refer or contact: firstname.lastname@example.org