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Dr Ritchie Williamson

PositionLecturer in Therapeutics
Location2.12 Norcroft Building
DepartmentSchool of Pharmacy and Medical Sciences
Telephone+44 (0) 1274 236073
EmailR.Williamson7@bradford.ac.uk
Twitter@RWilliamsonLab
LinkedInVisit my LinkedIn profile
ORCID0000-0003-4278-0909

Research Interests (key words only)

Dementia; Alzheimer’s disease; Ageing; protein O-GlcNAcylation; signalling pathways, Motor Neurone Disease

Teaching and Supervisory Responsibilities

MPharm

Module leader:

  • Stage 2 Senses, Thoughts & Movements 1
  • Stage 3 Senses, Thoughts & Movements 2

Unit lead:

  • Senses, Thoughts & Movements 2, Unit 4 – Neurological Problems

Personal Academic Tutor

Biomedical Sciences

  • Research Topics in Medicinal Biochemistry

Clinical Sciences

  • Central Nervous System – Mechanisms, Disorders & Therapeutics

Administrative Responsibilities

  • Member of Biomedical, Natural, Physical and Health Sciences Research Ethics Panel (BNPHS REP)
  • University of Bradford’s Human Tissue Authority Licence, Person Designate for the School of Pharmacy
  • Dementia Lead for the School of Pharmacy

Study History

  • BSc (Hons) in Biochemistry, 1996, University of Bath
  • MSc in Neuroscience, 1997, Institute of Psychiatry, King’s College London
  • PhD in Biochemistry, 2001, Institute of Psychiatry, King’s College London
  • Postgraduate Certificate of Higher Education Practice, 2015, University of Bradford

Professional History

  • 2011-2013: Postdoctoral Research Associate, College of Life Sciences, University of Dundee
  • 2008-2011: Postdoctoral Research Associate, Biomedical Research Institute, Ninewells Medical School, University of Dundee
  • 2004-2008: Postdoctoral Research Associate, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, King’s College London
  • 2001-2004: Alzheimer’s Society Research Fellow, Institute of Psychiatry, King’s College London

Professional Activities

  • Member British Neuroscience Association
  • Member Biochemical Society
  • Member British Society for Research on Ageing
  • Associate editor Frontiers in Neurodegeneration
  • External Examiner MSc in Neurosciences (King's College London)

Research Areas

Research in my laboratory focuses on identifying molecular mechanisms that underlie age-related cognitive decline and dementia. Increasing data from observational studies has identified a number of potentially modifiable risk factors associated with an increased risk of developing dementia including diabetes, obesity, physical inactivity, low educational attainment, depression, smoking, and hypertension. In addition, these risk factors are additive suggesting that common signaling pathways underlie these risk factors. A key observation of a number of these risk factors is that they display alterations in energy intake/expenditure and glucose metabolism.

It has previously been established that there is a link between altered energy intake, insulin sensitivity and poor cognitive performance. However, the precise molecular mechanisms that underlies the observed decrease in cognitive performance remains to be established. One possible mechanism is protein O-GlcNAcylation (a glucose-dependent post translational modification). Protein O-GlcNAcylation is altered in Alzheimer’s disease.

Other than a well-established role in gene expression, how protein O-GlcNAcylation effects protein function is still to be fully determined. Work in my laboratory aims to elucidate the links between glucose-dependent alterations in protein modifications, nutritional status, and ageing to molecular mechanisms underlying dementia.

Current Projects

  • Differential gene expression associated with life-style risk factors for dementia (Alzheimer’s Research UK network grant –Yorkshire branch, 2016)
  • Real-time imaging of molecular mechanisms underlying synaptic dysfunction and neurodegeneration in Alzheimer's disease (Alzheimer’s Research UK equipment grant 2016)
  • Targeting the unfolded protein response to limit TDP-43 aggregation (Motor Neurone Disease Association - 2015)
  • Validation of an O-GlcNAcase inhibitor as a novel therapeutic agent against Alzheimer pathology (Alzheimer’s Research UK Pilot project grant, 2014)
  • Development and application of a novel substrate trap methodology to identify glucose dependent post-translational modifications and their relevance to ageing and Alzheimer’s (Royal Society research grant, 2014)

Research Collaborations

  • Professor Daan van Aalten (University of Dundee)
  • Professor Bettina Platt (University of Aberdeen)
  • Professor Marcus Rattray (University of Bradford)
  • Dr Craig Beall (University of Exeter)

Publications

Selvan N, Williamson R, Mariappa D, Campbell DG, Gourlay R, Ferenbach AT, Aristotelous T, Hopkins-Navratilova I, Trost M and van Aalten DMF. A mutant O-GlcNAcase enriches Drosophila developmental regulators. Nat. Chemical. Biology, 13: 882-887 (2017)

Grasso L, Suska O, Davidson L, Gonatopoulus-Pournatzis, Williamson R, Wasmus L, Wiedlich S, Peggie M, Stavridis M.P. and Cowling V.H. mRNA Cap methylation in pluripotency and differentiation. Cell Reports, 16(5): 1352-1365 (2016)

Malik B, Fernandes C, Usardi A., Williamson R, Kellie S, Anderton B. H. and Reynolds C. H. Transcriptomic analysis of oligomeric amyloid-β treated primary cortical neurons reveals dysregulation of genes involved in the biosynthesis of steroids and cholesterol , in Microarrays: Principles, Applications and Technologies, (James V Rogers, ed), pp. 269-295. Nova Science Publishers, Inc., New York (2014)

Killick R, Ribe EM, Al-Shawi R, Malik B, Hooper C, Fernandes C, Dobson R, Nolan PM, Lourdusamy A, Furney S, Lin K, Breen G, Wroe R, To AWM, Leroy K, Causevic M, Usardi A, Robinson M, Noble W, Williamson R, Lunnon K, Kellie S, Reynolds CH, Bazanet C, Hodges A, Brion JP, Stephenson J, Simons JP and Lovestone S. Clusterin regulates ß-amyloid toxicity via Dickkopf-1 driven induction of the wnt-PCP-JNK pathway. Mol. Psychiatry, 19(1): 88-98 (2014)

McNeilly AD, Williamson R, Balfour DJ, Stewart CA and Sutherland C. A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin. Diabetologia, 55(11): 3061-3070 (2012)

Williamson R, McNeilly AD and Sutherland C. Insulin resistance in the brain; an old-age or new-age problem? Biochemical Pharmacology, 84(6):737-45. (2012)

Malik B, Fernandes C, Killick R, Wroe R, Usardi A, Williamson R, Kellie S, Anderton BH and Reynolds CH. Oligomeric amyloid-ß peptide affects the expression of genes involved in steroid and lipid metabolism in primary neurons. Neurochem Int, 61(3):321-333. (2012)

Williamson R, van Aalten L, Mann DMA, Platt B, Plattner F, Bedford L, Mayer J, Howlett D, Usardi A, Sutherland C and Cole AR. CRMP2 hyperphosphorylation is characteristic of Alzheimer’s disease and not a feature common to other neurodegenerative diseases. J Alzheimers Dis, 27(3):615-25. (2011)

Usardi A, Pooler AM, Seereeram A, Reynolds CH, Derkinderen P, Anderton B, Hanger DP, Noble W and Williamson R. Tyrosine phosphorylation of tau regulates its interactions with Fyn SH2 domains, but not SH3 domains, altering the cellular localization of tau. FEBS J, 278(16):2927-37. (2011)

Scales TM, Derkinderen P, Leung K-Y, Byers HL, Ward MA, Price C, Bird IN, Perera T, Kellie S, Williamson R, Anderton BH and CH Reynolds. Tyrosine phosphorylation of tau by the Src family kinases Lck and Fyn. Mol Neurodegen, 6:12. (2011)

Williamson R, Sutherland C. Neuronal membranes are key to the pathogenesis of Alzheimer’s disease: the role of both raft and non-raft membrane domains. Curr Alzheimer Res. 8(2):213-221. (2011)

McNeilly AD, Williamson R, Sutherland C, Balfour DJ, Stewart CA. High fat feeding promotes simultaneous decline in insulin sensitivity and cognitive performance in a delayed matching and non-matching to position task. Behav Brain Res, 217(1):134-141. (2011)

Kickstein E, Krauss S, Thornhill P, Rutschow D, Zeller R, Sharkey J, Williamson R, Fuchs M, Kohler A, Glossmann H, Schneider R, Sutherland C, Schweiger S. Biguanide metformin acts on tau phosphorylation via mTor/protein phosphatase (PP2A) signalling. Proc Natl Acad Sci, 107(50):21830-21835. (2010)

Williamson R, Thompson AJ, Abu M, Hye A, Usardi A, Lynham S, Anderton BH, Hanger DP. Isolation of detergent resistant microdomains from cultured neurons: detergent dependent alterations in protein composition. BMC Neurosci, 11:120. (2010)

Thompson AJ, Williamson R. Protocol for quantitative proteomics of cellular membranes and membrane rafts. Methods Mol Biol, 658:235-53. (2010)

Soutar MP, Kim WY, Williamson R, Peggie M, Hastie CJ, McLauchlan H, Snider WD, Gordon-Weeks PR, Sutherland C. Evidence that glycogen synthase kinase-3 isoforms have distinct substrate prepference in the brain. J Neurochem, 115(4):974-83. (2010)

Public/Academic/Stakeholder Engagement

I routinely give talks to the public on current research in dementia and participate in research open days at the University of Bradford.

2015 British Science Festival "Building Bridges between Care and Care Research in Dementia."

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