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 heads the EU IMI Consortium IMPRiND which aims to delineate new mechanisms that are 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.
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 uses 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.
We are also interested in the role of mitochondrial dysfunction in hereditary forms of neurodegeneration and the study of circulating exosomes as biomarkers for Parkinson's disease prediction or stratification.
Key publications
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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), 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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Stem cell modeling of mitochondrial parkinsonism reveals key functions of OPA1.
Journal article
Jonikas M. et al, (2018), Ann Neurol, 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 of USA
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Lysosome-dependent pathways as a unifying theme in Parkinson's disease.
Journal article
Tofaris GK., (2012), Mov Disord, 27, 1364 - 1369
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Ubiquitin ligase Nedd4 promotes alpha-synuclein degradation by the endosomal-lysosomal pathway.
Journal article
Tofaris GK. et al, (2011), Proc Natl Acad Sci U S A, 108, 17004 - 17009
Recent publications
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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
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The Phenotypic Continuum of ATPLA3-Related Disorders.
Journal article
Vezyroglou A. et al, (2022), Neurology
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Initiation and progression of α-synuclein pathology in Parkinson's disease.
Journal article
Tofaris GK., (2022), Cell Mol Life Sci, 79
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Longitudinal changes of early motor and cognitive symptoms in progressive supranuclear palsy: the OxQUIP study.
Journal article
Pereira MF. et al, (2022), BMJ Neurol Open, 4
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Multiplexed Profiling of Extracellular Vesicles for Biomarker Development.
Journal article
Jiang C. et al, (2021), Nanomicro Lett, 14
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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), Nat Commun, 12