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Prof Rohan de Silva
1 Wakefield Street
Prof Rohan de Silva profile picture
  • Professor of of Molecular Neuroscience
  • Clinical and Movement Neurosciences
  • UCL Queen Square Institute of Neurology
  • Faculty of Brain Sciences

Born and raised in Sri Lanka, studied biochemistry at the Universität Bern in Switzerland and completed DPhil research at Lincoln College in Oxford. DPhil research project was with Professor Gordon Lowe, FRS at the Dyson Perrins Laboratory looking at structure-function relationships of a plant-based protease inhibitor of the activated Hageman factor (Factor XIIa) of the human blood coagulation cascade. First postdoctoral post at the Duke University Medical Center under Professor Allen Roses. Was involved in identification of presenilin 1 and mutations as cause of early-onset familial Alzheimer’s disease. Also carried out early work with the late Professor Tsunao Saitoh in identifying the non-amyloid component (NAC) and its larger precursor protein, NACP, that subsequently was recognised as alpha-synuclein, a central player in Parkinson’s disease and synucleinopathies.

 Moved back to the UK and worked at MRC Neurodegenerative Disorders Unit at Imperial College, under Dr Ambrish Patel. Project involved studies in primary cultures of the influence of inflammatory cytokines on alternative splicing of the amyloid precursor protein gene (APP).Then moved to the Reta Lila Weston Institute at the UCL Queen Square Institute of Neurology and started work on the alpha-synuclein, gene and tau with Professor Andrew Lees and subsequently, Professor Tom Warner. With fruitful collaborations with Professor Sir John Hardy, FRS, carried out extensive work to understand the functional genetics of tau.

Research Groups
Research Themes
Research Summary

In the last three decades, the discovery of inherited gene defects in the familial forms of Alzheimers disease (AD), Parkinsons disease (PD) and frontotemporal dementias with parkinsonism (FTLD-tau) and the study of the functions of their proteins within the context of the healthy and diseased neural cells has resulted in great leaps in our understanding of the pathogenic processes involved in these disorders. 

My primary research interest is the role of the tau gene (MAPT) and protein in neurodegeneration. MAPT, is mutated in familial FTLD-tau. Insoluble fibrillar aggregates of the microtubule-binding protein, tau (tangle pathology) characterise the intraneuronal pathological inclusions that are hallmarks of the large group of related neurological disorders called the tauopathies, which include AD and FTLD-tau, and the parkinsonian disorder, progressive supranuclear palsy (PSP). MAPT mutations affect either the microtubule-binding capacity, fibrillogenicity or the production of tau protein isoforms. In addition to inherited mutations it has been shown that common genetic variation in MAPT in the form of the H1 increases risk of PSP and corticobasal degeneration (CBD). We identified H1c, a sub-haplotype of H1, that accounts for the increased risk, with H1c causing higher MAPT transcription and production of the more fibrillogenic four-repeat isoforms of tau (4R-tau). We also identified a novel class of long non-coding RNA genes (MIR-NATs), paired with protein coding genes, including MAPT-AS1 at MAPT, that regulate gene expression by mediating ribosomal mRNA recruitment. In collaboration with Eisai Ltd, development of monoclonal antibodies targeting the microtubule-binding repeat domain of tau, led to E2814, a humanised anti-tau antibody that is currently in clinical trials for passive immunotherapy in AD. Current research also extends to proteostasis and the role of the unfolded protein response in tauopathies and understanding the structural basis of the diversity of four-repeat tau seeding strains.

01-OCT-2019 Professor of Molecular Neuroscience Queen Sq Institute of Neurology/Reta Lila Weston Institute University College London, United Kingdom
01-AUG-2007 – 30-SEP-2019 Reader in Neuroscience Queen Sq Institute of Neurology/Reta Lila Weston Institute UCL, United Kingdom
01-JUL-2005 – 31-AUG-2005 Visiting Researcher Neurogenetics Laboratory National Institute on Ageing/National Institutes of Health, United States
01-JAN-2003 – 30-JUL-2007 Honorary Lecturer/Honorary Senior Lecturer Reta Lila Weston Institute UCL Institute of Neurology, United Kingdom
01-AUG-2002 – 30-SEP-2002 Visiting Researcher Neurogenetics Laboratory Mayo Clinic, Jacksonville, United States
01-JAN-1999 – 31-DEC-2002 Senior Research Fellow Reta Lila Weston Institute UCL Institute of Neurology, United Kingdom
01-JAN-1998 – 31-DEC-1998 Research Assessor   National Lotteries Charities Board, United Kingdom
01-SEP-1996 – 30-AUG-1999 Senior Research Fellow MRC Neurodegenerative Disorders Unit Imperial College School of Medicine, United Kingdom
01-AUG-1995 – 30-AUG-1996 Senior Research Fellow Molecular Genetics Laboratory Marie Curie Research Institute, United Kingdom
15-JAN-1993 – 01-JUN-1995 Teaching Assistant Division of Neurology Duke University Medical Center, United States
01-DEC-1991 – 15-JUN-1995 Research Associate Joseph and Kathleen Bryan Alzheimer's Disease Research Ctr Duke University Medical Center, United States
10-OCT-1986 – 10-OCT-1987 Research Assistant Institut für Biochemie und Molekularbiologie Universität Bern, Switzerland
Academic Background
1991   Doctor of Philosophy University of Oxford
1987   Licentiate Universitat Bern
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