Contact information


george.tofaris@ndcn.ox.ac.uk


+44 (0)1865 234 304
Fax +44(0)1865 234 837


Benjamin Jeffrey (NHS)
Benjamin.Jeffrey@ouh.nhs.uk

Biography

George Tofaris graduated from the combined MB/PhD programme of Cambridge University 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. 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 is a Medical Research Fellow at Corpus Christi College and previously held 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

MRC Senior Clinical Fellow, Honorary Consultant Neurologist

  • Associate Professor
  • Medical Research Fellow, Corpus Christi College
  • Academic Lead for IMI Consortium IMPRiND

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 study of the ubiquitin pathway. It is now well established that transport of proteins or organelles to lysosomes and their subsequent degradation is especially relevant to Parkinson’s disease. An important signalling cascade in this pathway is the conjugation of a ubiquitin chain to protein-substrates or organelles such as mitochondria. 

We found that α-synuclein is ubiquitinated in human brain and discovered that this modification regulates the trafficking of α-synuclein to endosomes for degradation by lysosomes. We identified enzymes that regulate this process and showed in animal models that they modify α-synuclein-induced toxicity. Because the cellular accumulation of α-synuclein is causatively linked to neurodegeneration, our findings suggest novel mechanistic insights into the pathogenesis of Parkinson's and related diseases, which are the focus of current studies.

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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