Sheffield Institute for
Translational Neuroscience

Professor Stephen B Wharton PhD FRCPath

Professor of Neuropathology, University of Sheffield

Consultant Neuropathologist, Sheffield Teaching Hospitals NHS Foundation Trust


Research Interests

Professor Wharton’s research interests are focused on the cellular and molecular pathology of brain ageing and its relationship to the pathology of neurodegenerative diseases, particularly Alzheimer’s disease. His major areas of interest are in:

  • Understanding the pathological basis of dementia through involvement with the MRC Cognitive Function and Ageing Study, which takes a population-based approach to the neuropathology of dementia.
  • Investigating the cellular and molecular pathology of astrocytes, neurones and endothelium as components of the neurovascular unit in brain ageing and in the pathogenesis of dementia.
  • The pathogenesis of white matter pathology in brain ageing and its contribution to dementia.
  • The pathology of motor neurone diseases and tissue banking in collaboration with Prof Ince and Prof Shaw.

Current Projects

  • Role of microRNAs in ageing at the blood brain barrier: integrated studies in human and mouse models (BBSRC).
  • Impaired tight junction protein signalling in astrocytes in Alzheimer’s disease (ARUK)
  • Oxidative DNA damage and transcriptional impairment in brain ageing as an early contributor to cognitive impairment (MRC)
  • Impairment of insulin signalling pathways in brain ageing and the progression of Alzheimer type pathology (ARUK)

Current funding sources

  • Alzheimer’s Research UK, MRC, BBSRC

External collaborations

  • Dr Fiona Matthews and Prof Carol Brayne, University of Cambridge. The MRC Cognitive Function and Ageing Study.
  • Dr Ignacio Romero and Margaret Saffery, Open University. Endothelial pathology in brain ageing.

Research Team

  • Dr Julie Simpson
  • Dr Claire Garwood
  • Dr Emily Goodall,
  • David Drew

PhD students

  • Sufana Al-Mashadi,
  • Sarah Morgan,
  • Laura Ratcliffe
  • Irina Vazquez Villasenor

BMedSci

  • Ryan Mathur

Publications

Selected publications (last 5 years)

Richardson K, Allen S, Mortiboys H, Grierson AJ, Wharton SB, Ince PG, Shaw PJ, Heath PR. The effect of SOD1 mutation on cellular bioenergetic profile and viability in response to oxidative stress, and influence of mutation type. PLoS ONE 8(6):e68256.

Garwood C, Faizullabhoy A, Wharton SB, Ince PG, Heath P, Shaw PJ, Baxter L, Gelsthorpe C, Matthews FE, Brayne C, Simpson JE, the MRC Cognitive Function and Ageing Neuropathology Study Group. Calcium dysregulation in relation to Alzheimer-type pathology in the ageing brain. Neuropathol Appl Neurobiol 2013; 39:788-799.

Brockington A, Ning K, Heath PR, Wood E, Kirby J, Fusi N, Lawrence N, Wharton SB, Ince PG, Shaw PJ. Unravelling the enigma of selective vulnerability in neurodegeneration: motor neurons show distinct gene expression characteristics and decreased susceptibility to excitotoxicity. Acta Neuropathol 2013 125:95-109

Lace G, Ince PG, Brayne C, Savva GM, Matthews FE, de Silva R, Simpson JE, Wharton SB, On behalf of MRC-CFAS. Mesial temporal astrocyte tau pathology in the MRC-CFAS ageing brain cohort. Dement Geriatr Cogn Disord 2012; 34:15-24.

Waller R, Woodroofe, MN, Francese S, Heath PR, Wharton SB, Ince PG, Sharrack B, Simpson JE. Isolation of enriched glial populations from post-mortem human CNS material by immuno-laser capture microdissection. J Neurosci Methods 2012; 208:108-113.

Viggars AP, Wharton SB, Simpson JE, Matthews FE, Brayne C, Savva GM, Garwood C, Drew D, Shaw PJ, Ince PG. Alterations in the blood brain barrier in ageing cerebral cortex in relationship to Alzheimer-type pathology: a study in the MRC-CFAS population neuropathology cohort. Neurosci Lett 2011; 505:25-30.

Simpson JE, Ince PG, Shaw PJ, Heath PR, Raman R, Garwood CJ, Gelsthorpe C, Baxter L, Forster G, Matthews FE, Brayne C, Wharton SB, on behalf of the MRC Cognitive Function and Ageing Neuropathology Study Group. Microarray analysis of the astrocyte transcriptome in the ageing brain: relationship to Alzheimer’s pathology and APOE genotype. Neurobiol Aging 2011; 32:1795-807.

Kirby J, Ning K, Ferraiuolo L, Heath PR, Ismail A, Kuo S-W, Valori CF, Cox L, Sharrack B, Wharton SB, Ince PG, Shaw PJ, Azzouz M. Phosphatase and tensin homologue/protein kinase B pathway linked to motor neuron survival in human superoxide disumutase 1-related amyotrophic lateral sclerosis. Brain 2011; 134:506-17

Simpson JE, Wharton SB, Cooper J, Gelsthorpe C, Baxter L, Forster G, Shaw PJ, Savva G, Matthews FE, Brayne C, Ince PG. Alterations of the blood-brain barrier in cerebral white matter lesions in the ageing brain. Neurosci Lett 2010; 486:246-51.

Simpson JE, Ince  PG, Haynes LJ, Theaker R, Gelsthorpe C, Baxter L, Forster G, Lace GL, Shaw PJ, Matthews FE, Savva GM, Brayne C, Wharton SB, on behalf of the MRC Cognitive Function and Ageing Neuropathology Study Group. Population Variation in Oxidative Stress and Astrocyte DNA Damage in Relation to Alzheimer-type Pathology in the Ageing Brain. Neuropathol Appl Neurobiol 2010; 36:25-40.

Matthews FE, Brayne C, Lowe J, McKeith I, Wharton SB, Ince P. Epidemiological pathology of dementia: attributable-risk at death in the Medical Research Council Cognitive Function and Ageing Study. PLoS Med 2009; 6(11): e1000180.

Savva GM*, Wharton SB*,  Ince PG, Forster G, Matthews FE, Brayne C, on behalf of MRC-CFAS. Age, neuropathology and dementia. N Engl J Med 2009; 360:2302-2309. [* joint first authors]. This paper is the subject of an accompanying editorial: DC Ewbank and SE Arnold. Cool with plaques and tangles. N Engl J Med 2009; 360:2357-2359.

 SB Wharton, JP O’Callaghan, GM Savva, JAR Nicoll, F Matthews, JE Simpson, G Forster, PJ Shaw, C Brayne, PG Ince, on behalf of the MRC Cognitive Function and Ageing Neuropathology Study Group. Population variation in glial fibrillary acidic protein levels in brain ageing: relationship to Alzheimer-type pathology and dementia. Dem Geriat Cog Dis 2009; 27:465-473.

 Lace G, Savva G, Forster G, De Silva R, Brayne C, Matthews F, Barclay JJ, Dakin L, Ince PG, Wharton SB, on behalf of MRC-CFAS. Hippocampal tau pathology in an elderly neuropathology cohort: population variation and hierarchy of sub-regional involvement suggesting anterograde progression along neuroanatomical pathways. Brain 2009; 132:1324-1334.

 Simpson JE, Ince PG, Lace G, Forster G, Shaw PJ, Matthews F, Savva G, Brayne C, Wharton SB, on behalf of the MRC Cognitive Function and Ageing Neuropathology Study Group. Astrocyte phenotype in relation to Alzheimer-type pathology in the ageing brain. Neurobiol Aging 2010; 31:578-590.

Professional Activities

Editorial activities

  • Consulting editor, Neuropathology and Applied Neurobiology (2014-)
  • Editor-in-Chief, Neuropathology and Applied Neurobiology (2007-13)
  • Associate editor (for reviews), Histopathology (2003-2006)
  • Current editorial board membership – Neuropathology Applied Neurobiology

External professional activities – current and recent

  • Examiner in neuropathology for the Royal College of Pathologists (2005-)
  • Member British Neuropathological Society General Purposes and Finance Committee (2007-13).
  • Secretary to the Professional Affairs Committee, British Neuropathological Society (2004-2007)

Membership of associations and societies - current

  • International Society for Neuropathology
  • British Neuropathological Society
  • British Medical Association

Biography

Career History

  • 2014 - present:
    Professor in Neuropathology, Sheffield University
  • 2000 - 2014:  
    Reader in Neuropathology, Sheffield University
  • 1997 - 2000:
    Senior lecturer / honorary consultant in Neuropathology, Edinburgh University
  • 1994 – 1997:
    Senior registrar in Neuropathology, Addenbrookes Hospital, Cambridge

Qualifications

  • PhD (by publications), University of Sheffield, 2013
  • FRCPath awarded 2005
  • MRCPath in Neuropathology 1997
  • DipRCPath Histopathology 1995
  • MSc University of Cambridge 1995
  • MBBS London University 1988
  • BSc (Hons) University of London 1985

Contact Details

Department of Neuroscience
Sheffield Institute for Translational Neuroscience
University of Sheffield
Room B34
385a Glossop Road
Sheffield
S10 2HQ

F: +44 (0)114 22 22235
E: s.wharton@sheffield.ac.uk

Secretary:
Jo Brodie (Mon, Tue)
T: +44 (0)114 22 22262
E: j.brodie@sheffield.ac.uk