Contact information
+44 (0)1865 234 304
Fax +44(0)1865 234 837
Ellie Slattery (NHS)
Ellie.Slattery@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
Biography
George Tofaris graduated with Distinction from the MB/PhD programme at the University of Cambridge (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 the University of 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 employs genetic screens, proteomics and transcriptomics in iPSC-based models of increasing cellular complexity as well as the study of biosamples from clinical cohorts.
Of particular interest to my group is the cellular trafficking and aggregation of α-synuclein, a key protein in Parkinson's disease, and how it interacts with organelles. 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 patient-derived iPSC models to identify modifiers of its turnover and aggregation.
Our cellular studies 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 in serum and performed the largest multicentre studies demonstrating their value in the prediction and stratification of Parkinson's and related conditions.
Key publications
Single extracellular vesicle detection assay identifies membrane-associated α-synuclein as an early-stage biomarker in Parkinson’s disease
Journal article
Yan S. et al, (2025), Cell Reports Medicine, 6, 101999 - 101999
Neuronally Derived Extracellular Vesicle α-Synuclein as a Serum Biomarker for Individuals at Risk of Developing Parkinson Disease
Journal article
Yan S. et al, (2024), JAMA Neurology, 81, 59 - 59
Monitoring α-synuclein ubiquitination dynamics reveals key endosomal effectors mediating its trafficking and degradation
Journal article
Zenko D. et al, (2023), Science Advances, 9
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
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
Stem cell modeling of mitochondrial parkinsonism reveals key functions of OPA1
Journal article
Jonikas M. et al, (2018), Annals of Neurology, 83, 915 - 925
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
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
Compartment-specific correlation of pathological α-synuclein in prodromal Parkinson's disease
Journal article
Röttgen S. et al, (2026), Parkinsonism & Related Disorders, 144, 108178 - 108178
Palindrome-mediated 16p13.3 triplications cause a recognizable neurodegenerative disorder with ataxia.
Journal article
Fasham J. et al, (2026), Am J Hum Genet, 113, 221 - 233
Serum p‐tau217 Is a Prognostic Indicator of Cognitive Impairment in Idiopathic REM Sleep Behavior Disorder
Journal article
Yan S. et al, (2025), Annals of Neurology
In vivo validation of novel non-invasive PHP.eB AAVs as a potential therapeutic approach for alpha-synucleinopathies.
Journal article
Fouka M. et al, (2025), Acta Neuropathol Commun, 13
Decade‐Long Prodrome on Neuroimaging: Unique Insight into Probable Corticobasal Degeneration
Journal article
Tai XY. et al, (2025), Movement Disorders, 40, 1727 - 1729
Treatment Selection and Prioritization for the EJS ACT‐PD MAMS Trial Platform
Journal article
Gonzalez‐Robles C. et al, (2025), Movement Disorders, 40, 1307 - 1317