Contact information
+44 (0)1865 234 304
Fax +44(0)1865 234 837
Ellie Slattery (NHS)
Neurology.Parkinsons@ouh.nhs.uk
Research groups
Colleges
Websites
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Kavli Institute for Nanoscience Discovery
Multidisciplinary Institute
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Inhibiting Misfolded protein Propagation In Neurodegenerative Disease
International consortium
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Oxford Parkinson's Disease Centre
Oxford Consortium
Biography
George Tofaris graduated from the combined MB/PhD programme of Cambridge University (Trinity College) in 2003. He completed his general medical training at the National Hospital for Neurology, Hammersmith, Royal Brompton and Royal Free hospitals in London in 2006. He worked for a year at the Neurology Department of the Austin hospital, an affiliate of Melbourne University. He was appointed Clinical Lecturer at Oxford in 2007 and completed his training in Clinical Neurology in 2011 with subspecialty training in Movement Disorders at the National Hospital for Neurology and Neurosurgery. Between 2008-09, he was a Lefler Fellow in Cell Biology at Harvard Medical School. In 2012, he was awarded a Wellcome Trust Intermediate Clinical Fellowship and the Wellcome-Beit Prize to further his research and after a short visit at the Brigham and Women's Hospital in Boston, he established his research group at Oxford. In 2020, he was awarded an MRC Senior Clinical Fellowship. He also established and led the EU IMI Consortium IMPRiND which investigated mechanisms relevant to the progression of pathology in Parkinson's and Alzheimer's disease. He held a Medical Research Fellowship at Corpus Christi College and previously a Todd-Bird Junior Research Fellowship in Medicine at New College. As a clinically active Consultant Neurologist at the John Radcliffe hospital, he covers acute as well as general outpatient neurology and leads regional specialist clinics in Movement and Neurogenetic Disorders. He is also the Oxford PI for Clinical Trials testing precision therapies in Parkinson's disease.
George Tofaris
PhD, MBBChir, FRCP
Professor of Neurology and Translational Neuroscience
- MRC Senior Clinical Fellow
- Honorary Consultant Neurologist
Molecular mechanisms of neurodegeneration
Research Summary
My research aim is to delineate cellular pathways in protein quality control that could inform the development of novel biomarkers and targeted therapies in neurodegenerative and neurogenetic disorders. To this end, my group is currently using forward genetics, proteomics and transcriptomics in models of increasing cellular complexity, including patient-derived induced pluripotent stem cells (iPSC).
Of particular interest to my group is the cellular trafficking and aggregation of α-synuclein, a key protein in Parkinson's disease. We found that α-synuclein is ubiquitinated in human brain and discovered that this modification regulates the localisation of α-synuclein to endosomes for degradation by lysosomes. We have developed iPSC-based models to identify modifiers of its turnover and aggregation.
Our studies inside cells suggested a rationale for endosome-derived extracellular vesicle alpha-synuclein as a biomarker in Parkinson's disease. We have developed improved methodologies to immunocapture neuronally-derived extracellular vesicles from serum and performed multi-centre studies demonstrating their value in the prediction and stratification of Parkinson's and related conditions.
We are also interested in the role of mitochondrial dysfunction in hereditary forms of neurodegeneration.
Key publications
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Monitoring α-synuclein ubiquitination dynamics reveals key endosomal effectors mediating its trafficking and degradation
Journal article
Zenko D. et al, (2023), Science Advances, 9
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Phenotypic manifestation of α-synuclein strains derived from Parkinson’s disease and multiple system atrophy in human dopaminergic neurons
Journal article
Tanudjojo B. et al, (2021), Nature Communications, 12
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Serum neuronal exosomes predict and differentiate Parkinson’s disease from atypical parkinsonism
Journal article
Jiang C. et al, (2020), Journal of Neurology, Neurosurgery & Psychiatry, 91, 720 - 729
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Stem cell modeling of mitochondrial parkinsonism reveals key functions of OPA1
Journal article
Jonikas M. et al, (2018), Annals of Neurology, 83, 915 - 925
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Deubiquitinase Usp8 regulates α-synuclein clearance and modifies its toxicity in Lewy body disease
Journal article
Alexopoulou Z. et al, (2016), Proceedings of the National Academy of Sciences, 113
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Ubiquitin ligase Nedd4 promotes α-synuclein degradation by the endosomal–lysosomal pathway
Journal article
Tofaris GK. et al, (2011), Proceedings of the National Academy of Sciences, 108, 17004 - 17009
Recent publications
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Normal and pathogenic variation of RFC1 repeat expansions: implications for clinical diagnosis.
Journal article
Dominik N. et al, (2023), Brain
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Monitoring α-synuclein ubiquitination dynamics reveals key endosomal effectors mediating its trafficking and degradation
Journal article
Zenko D. et al, (2023), Science Advances, 9
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Methodological considerations in neuronal extracellular vesicle isolation for α-synuclein biomarkers
Journal article
Yan S. et al, (2023), Brain
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Alternating Magnetic Field-Promoted Nanoparticle Mixing: The On-Chip Immunocapture of Serum Neuronal Exosomes for Parkinson’s Disease Diagnostics
Journal article
Sharafeldin M. et al, (2023), Analytical Chemistry
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Multiplexed Profiling of Extracellular Vesicles for Biomarker Development
Journal article
Jiang C. et al, (2022), Nano-Micro Letters, 14
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The Phenotypic Continuum of ATP1A3-Related Disorders.
Journal article
Vezyroglou A. et al, (2022), Neurology, 99, e1511 - e1526
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Heterozygous UCHL1 loss-of-function variants cause a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy.
Journal article
Park J. et al, (2022), Genet Med