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Department of Veterinary Medicine

Cambridge Veterinary School

Studying at Cambridge

 

Professor Alun Williams

Professor Alun Williams

Professor of Veterinary Diagnostic Pathology

Director of Teaching (elect)

Director of Studies in Clinical Veterinary Medicine (Wolfson College)

Pathology of blast injury

Mechanisms of neurodegeneration in chronic neurodegenerative diseases – prion diseases, Alzheimer’s disease and Parkinson’s.

Mechanisms underpinning pathogenesis of Streptococcus suis type 2 meningitis

Alun Williams is interested in taking PhD students.

Alun Williams is available for consultancy.


Office Phone: +44 (0)1223 337640

Biography:

PhD, University of Cambridge, 1989

BVMS, University of Glasgow, 1985

 

Other qualifications:

Member, Royal College of Veterinary Surgeons, 1985

Diplomate, European College of Veterinary Pathology, 1999

Fellow, Higher Education Academy, 2009

 

Posts held

2009-date: Professor of Veterinary Diagnostic Pathology, University of Cambridge

Responsible for provision of pathology diagnostic services and pathology support to research projects; provision of teaching in veterinary pathology; Director (elect) of Teaching, Chair of Department’s Ethics and Welfare Committee, Co-ordinator, Senior Clinical Training Scholarship programme. From 1997 onwards, supervision of 5 PhD students, 2 Masters students (research Masters), and co-supervision of 6 successful pathology Training Scholars (Board qualifications)

2003-2009: Professor of Pathology and Infectious Diseases, The Royal Veterinary College, University of London

2001-2003: Reader in Veterinary Pathology, University of Glasgow

1997-2001: Senior Lecturer in Veterinary Pathology, University of Glasgow

1990-1997: Veterinary Research Officer and Named Veterinary Surgeon, Institute for Animal Health, Edinburgh

1989-1990: MRC University Research Fellowship

1985-1988: AFRC Veterinary Schools’ Fellowship

1985-1990: Locum Veterinary Surgeon (various practices – full time 1985; part-time thereafter)

Subject groups/Research projects

Neurosciences:

Research Interests

Alun Williams leads a research group whose current focus in determining the mechanism of neurodegeneration in chronic neurodegenerative diseases, particularly prion diseases such as Creutzfeldt-Jakob Disease, and also Alzheimer’s disease and Parkinson’s. For all these three peptides, the concentration required to cause synaptic damage in cultured neurons is 1/1000 that required to cause cell death – reflecting the pathogenesis of these diseases in vivo where synaptic loss occurs prior to cell death, and when concentrations of the toxic peptide in the affected areas of the brain are lower. These studies have also clearly demonstrated that cross-linking molecules of the outer membrane leaflet protein PrP (prion protein) causes dense packing of their GPI anchor within lipid rafts – and this triggers a signaling cascade that results in synapse loss and cell death. These signaling pathways include the phospholipase-cyclooxygenase-prostaglandin pathway as inhibition of that pathway abrogates toxic effects of PrP and the Ab peptide of Alzheimer’s disease. Activation of this pathway is lipid-raft dependent as dispersion of rafts inhibits the pathway activation and PrP toxicity. Indeed, the group’s recent studies have demonstrated that Ab toxicity is mediated through aggregation of PrP GPI anchors in the lipid rafts, confirming a common toxicity pathway in these two diseases. In contrast, the a-synuclein protein of Parkinson’s appears to act via a non-PrP mediated manner. In complementary studies, Alun’s group has demonstrated, for the first time, that activation of phospholipase A2 by abnomal forms of PrP at the cell surface results in it binding to type III tubulin, indicating that alterations in neuronal transport systems may contribute to the degenerative effects of these peptides. This work has been funded by a succession of EU contracts. He collaborates with Steve Gentleman (Imperial College, London) in a project funded by Parkinson’s UK aimed at identifying markers of early synaptic degeneration in Parkinson’s, with the aim not only of furthering understanding of pathogenesis and spread of this disease within the brain, but in a potential diagnostic indicator of neurodegenerative disease.

Alun is also part of a collaboration with Kate Brown, Chiara Bo, Ben Butler, the Department of Physics, University of Cambridge and the Institute of Shock Physics, Imperial College, London investigating the pathological effects of blast injury (shock wave injury) to a range of tissues. This project is funded by the Royal British Legion.

In addition, Alun has an interest in the pathogenesis of Streptococcus suis type 2 meningtits, and supports clinical research conducted by colleagues within the Department, and provides pathology support to several studies within University of Cambridge and allied Institutes.

Collaboratorscroc

  • Dr Clive Bate, RVC, University of London
  • Dr Steve Gentleman, Imperial College, London
  • Dr Kate Brown, University of Austin, Texas, and Imperial College, London
  • Dr Chiara Bo, Imperial College, London
  • Ben Butler, University of Cambridge (PhD student)
  • Dr Mark Treherne, Senexis, UK
  • Prof Andrew Doig, University of Manchester
  • Prof Mario Salmona, Mario Negri Institute, Milan
  • Prof Gianluigi Forloni, Mario Negri Institute, Milan
  • Dr. Marco Gobbi, Mario Negri Institute, Milan
  • Prof Fabrizio Tagliavini, National Neurological Institute, “Carlo Besta”, Milan

Keywords

  • Neurodegeneration
  • Alzheimer's
  • Prion
  • Pathogenesis
  • PrP
  • Pathology
  • Blat injury
  • Parkinsons'
  • Streptococcus suis type 2

Key Publications

Amijee H, Bate C, Williams A, Virdee J, Jeggo R, Spanswick D, Scopes DI, Treherne JM, Mazzitelli S, Chawner R, Eyers CE & Doig AJ. (2012) The N-methylated peptide SEN304 powerfully inhibits Aβ(1-42) toxicity by perturbing oligomer formation. Biochemistry, 51, 8338-8352.

Bate C & Williams A. (2012) Clustering of sialylated glycosylphosphatidylinositol anchors mediates PrP-induced activation of cytoplasmic phospholipase A2 and synapse damage.

Prion, 6, 350-353.

Bate C & Williams A. (2012) Neurodegeneration induced by clustering of sialylated glycosylphosphatidylinositols of prion proteins. J Biol Chem, 287, 7935-7944.

Bate C & Williams A. (2011) Amyloid-{beta}-induced synapse damage is mediated via cross-linkage of the cellular prion protein. J Biol Chem, 286, 37955-37963.

Bate C & Williams A. (2011) Monoacylated cellular prion protein modifies cell membranes, inhibits cell signaling, and reduces prion formation. J Biol Chem, 286, 8752-8758.

Manzoni C, Colombo L, Bigini P, Diana V, Cagnotto A, Messa M, Lupi M, Bonetto V, Pignataro M, Airoldi C, Sironi E, Williams A & Salmona M. (2011) The molecular assembly of amyloid Aβ controls its neurotoxicity and binding to cellular proteins. PLoS ONE, 6(9).

Bate C, Tayebi M, & Williams A. (2010) Glycosylphosphatidylinositol anchor analogues sequester cholesterol and reduce prion formation. J Biol Chem, 285, 22017-22026.

Bate C, Tayebi M & Williams A. (2010) The glycosylphosphatidylinositol anchor is a major determinant of prion binding and replication. Biochem J, 428, 95-101.

Bate C, Tayebi M & Williams A. (2010) Phospholipase A2 inhibitors protect against prion and Aβ mediated synapse degeneration. Mol Neurodegeneration, 5, 13.

Bate C, Gentleman S & Williams A. (2010) α-synuclein induced synapse damage is enhanced by amyloid-β1-42. Mol Neurodegeneration, 5, 55.