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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

Serum neuronal exosomes predict and differentiate Parkinson's disease from atypical parkinsonism

Journal article

Jiang C. et al, (2020), Journal of Neurology, Neurosurgery and 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 of the United States of America, 113, E4688 - E4697

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 of the United States of America, 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 and Related Disorders, 144

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 Neuropathologica Communications, 13

Treatment Selection and Prioritization for the EJS ACT-PD MAMS Trial Platform

Journal article

Gonzalez-Robles C. et al, (2025), Movement Disorders