I graduated from the combined MB/PhD programme of Cambridge University, Trinity College, and completed my general medical training at the National Hospital for Neurology, Hammersmith, Royal Brompton and Royal Free hospitals in London. I worked for a year at the Neurology Department of the Austin hospital in Australia and was appointed Clinical Lecturer at Oxford in 2007. Between 2008-09, I was a Lefler research fellow at Harvard Medical School. I completed my training in Clinical Neurology in 2011 and subsequently awarded the Wellcome-Beit Prize Fellowship to establish my research group at Oxford. I am the academic lead for 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. As a clinically active Consultant Neurologist at the John Radcliffe hospital, I cover acute neurology and lead regional specialist clinics in Movement and Neurogenetic Disorders.
Research and Teaching
My research investigates cellular mechanisms that regulate the clearance of misfolded proteins or damaged organelles in age-related neurodegenerative disorders with a primary focus on Parkinson’s disease. An important signalling cascade in this respect is the conjugation of a ubiquitin chain to protein-substrates or organelles such as mitochondria. I previously demonstrated that the key pathogenic protein in Parkinson’s disease, called α-synuclein, is degraded in a ubiquitin-dependent manner and identified relevant enzymes that mediate this process. Currently, we are employing a multifaceted approach encompassing forward genetics, proteomics and transcriptomics in models of increasing cellular complexity, including the use of patient-derived induced pluripotent stem cells (iPSC) to:
(1) Map the relevant enzymes that regulate alpha-synuclein homeostasis or dopaminergic cell viability more broadly.
(2) Understand how disruption of these mechanisms leads to disease.
(3) Translate this fundamental knowledge into rational mechanism-based therapies.
(4) Develop biomarkers to monitor alpha-synuclein targeting therapies in patients.
Jonikas M, Madill M, Mathy A, Zekoll T, Zois CE, Wigfield S, Kurzawa-Akanbi M, Browne C, Sims D, Chinnery PF, Cowley SA, Tofaris GK. Stem cell modeling of mitochondrial parkinsonism reveals key functions of OPA1. Ann Neurol. 2018 May;83(5):915-925.
Li Q, Tofaris GK, Davis JJ. Concentration-Normalized Electroanalytical Assaying of Exosomal Markers. Anal Chem. 2017 Mar 7;89(5):3184-3190.
Alexopoulou Z, Lang J, Perrett RM, Elschami M, Hurry ME, Kim HT, Mazaraki D, Szabo A, Kessler BM, Goldberg AL, Ansorge O, Fulga TA, Tofaris GK. Deubiquitinase Usp8 regulates alpha-synuclein clearance and modifies its toxicity in Lewy body disease. Proc Natl Acad Sci U S A. 2016 Aug 9;113(32):E4688-97.
Davies SE, Hallett PJ, Moens T, Smith G, Mangano E, Kim HT, Goldberg AL, Liu JL, Isacson O,Tofaris GK. Enhanced ubiquitin-dependent degradation by Nedd4 protects against alpha-synuclein accumulation and toxicity in animal models of Parkinson's disease. Neurobiol Dis. 2014 Apr;64:79-87.
Tofaris GK, Kim HT, Hourez R, Jung JW, Kim KP, Goldberg AL. Ubiquitin ligase Nedd4 promotes alpha-synuclein degradation by the endosomal-lysosomal pathway. Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):17004-9.