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
Biography
George Tofaris graduated with Distinction from the 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 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. 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.
We are also interested in the role of mitochondrial dysfunction in hereditary forms of neurodegeneration.
Key publications
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Journal article
Yan S. et al, (2023), JAMA Neurol
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Journal article
Zenko D. et al, (2023), Sci Adv, 9
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Journal article
Tanudjojo B. et al, (2021), Nat Commun, 12
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Serum neuronal exosomes predict and differentiate Parkinson’s disease
from atypical Parkinsonism
Journal article
TOFARIS G., (2020), Journal of Neurology, Neurosurgery and Psychiatry
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Journal article
Jonikas M. et al, (2018), Ann Neurol, 83, 915 - 925
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Journal article
Alexopoulou Z. et al, (2016), Proceedings of the National Academy of Sciences of USA
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Journal article
Tofaris GK. et al, (2011), Proc Natl Acad Sci U S A, 108, 17004 - 17009
Recent publications
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Neuronally Derived Extracellular Vesicle α-Synuclein as a Serum Biomarker for Individuals at Risk of Developing Parkinson Disease.
Journal article
Yan S. et al, (2023), JAMA Neurol
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Detailed Analysis of ITPR1 Missense Variants Guides Diagnostics and Therapeutic Design.
Journal article
Tolonen JP. et al, (2023), Mov Disord
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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, (2023), Genet Med, 25
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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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Towards a multi-arm multi-stage platform trial of disease modifying approaches in Parkinson's disease.
Journal article
Foltynie T. et al, (2023), Brain, 146, 2717 - 2722
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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), Sci Adv, 9
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Methodological considerations in neuronal extracellular vesicle isolation for α-synuclein biomarkers
Journal article
Yan S. et al, (2023), Brain