Professor Stephen B Whartonwharton

Professor and Honorary consultant in Neuropathology

Department of Neuroscience
Sheffield Institute of Translational Neuroscience
University of Sheffield
385a Glossop Road
Sheffield
S10 2HQ
Email: s.wharton@sheffield.ac.uk

Secretary: Bev Carter
Tel: +44 (0)114 22 22295
Email: bev.carter@sheffield.ac.uk

Career History

2014 – current: Professor in Neuropathology – University of Sheffield
2011 – 2013: Clinical Reader / honorary consultant in Neuropathology – University of Sheffield
2001 – 2010: Senior lecturer / honorary consultant in Neuropathology – University of Sheffield
1997 - 2001: Senior lecturer / honorary consultant in Neuropathology – Edinburgh University

Qualifications

BSc (hons), MBBS, MSc, PhD, FRCPath

Teaching

  • Module leader: Pathology and Modelling of Neurodegeneration, MSc Translational Neuropathology
  • MSc lectures – Translational Neuroscience and Translational pathology
  • MBBS lectures – Preclinical neurosciences
  • Neuroanatomy dissection teaching
  • Supervisor SSC research projects
  • Supervisor MSc research projects

Research

My research interests are in the pathology and pathogenesis of neurodegenerative disorders, particularly the dementias and their relationship to brain ageing.

Major projects:

  • Pathology of cognitive impairment – through involvement with the MRC Cognitive Function and Ageing Study (www.cfas.ac.uk). This study takes a population-based approach to the neuropathology of dementia.
  • The effects of diabetes on the brain.
  • The role of astrocytes in brain ageing and Alzheimer’s Disease.
  • Oxidative and nucleic acid damage in brain ageing.
  • White matter pathology in dementia
  • Gene expression changes in ageing endothelium and the blood brain barrier.
  • Motor system pathology and tissue banking in collaboration with Prof Ince and Prof Shaw.

Funding

My work has been funded by Alzheimer’s Research UK, Alzheimer’s Society, MRC, BBSRC

Editorial activities

  • Member of editorial board and Consulting Editor, Neuropathology and Applied Neurobiology (2014-current)
  • Editor-in-Chief, Neuropathology and Applied Neurobiology (2007-13)
  • Associate editor, Histopathology (2003-2006)

External professional activities

  • Member of Alzheimer’s Research UK Grant Review Board (2016 -)
  • Examiner in neuropathology for the Royal College of Pathologists (2005-)
  • Member British Neuropathological Society General Purposes and Finance Committee (2006-2013).
  • Secretary to the Professional Affairs Committee, British Neuropathological Society (2004-2007)

Membership of associations and societies - current

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

Selected publications (last 10 years)

1. Ince PG, Minett T, Forster G, Brayne C, Wharton SB. Microinfarcts in an older population-representative brain donor cohort (MRC-CFAS): Prevalence, relation to dementia and mobility, and implications for the evaluation of cerebral Small Vessel Disease. Neuropathol Appl Neurobiol Early online doi10.1111/nan.12363.

2. Appleby-Mallinder C, Wyles MD, Simpson JE, Wharton SB, Ince PG, Heath PR. Expression microdissection of enriched cell populations from archival brain tissue. J Neurosci Methods 2016: 268:125-130.

3. * Matthews FE, Stephan BCM, Robinson L, Jagger C, Barnes LE, Arthur A, Brayne C, Cognitive Function and Ageing Studies (CFAS) Collaboration*. A two decade dementia incidence comparison from the Cognitive Function and Ageing Studies I and II. Nat Commun 2016; 7:11398. [*Member of the Collaborative Group].

4. Wharton SB, Minett T, Drew DR, Forster G, Matthews F, Brayne C, Ince PG. Epidemiological pathology of tau in the ageing brain. Application of staging for neuropil threads (BrainNet Europe Protocol) to the MRC Cognitive Function and Ageing Brain Study. Acta Neuropathol Commun 2016; 4:11.

5. Fluteau A, Ince PG, Minett T, Matthews FE, Brayne C, Garwood CJ, Ratcliffe LE, Morgan S, Heath PR, Shaw PJ, Wharton SB, Simpson JE; MRC Cognitive Function Ageing Neuropathology Study Group. The nuclear retention of transcription factor FOXO3a correlates with a DNA damage response and increased glutamine synthetase expression by astrocytes suggesting a neuroprotective role in the ageing brain. Neurosci Lett 2015; 609:11-17. doi: 10.1016/j.neulet.2015.10.001

6. Garwood CJ, Ratcliffe LE, Morgan SV, Simpson JE, Owens H, Vazquez-Villasenor I, Heath PR, Romero IA, Ince PG, Wharton SB. Insulin and IGF-1 signalling pathways in human astrocytes in vitro and in vivo; characterisation, subcellular localisation and modulation of the receptors. Mol Brain 8:51 DOI 10.1186/s13041-015-0138-6.

7. Stratmann K, Heinsen H, Korf HW, Del Turco D, Ghebremedhin E, Seidel K, Bouzrou M, Grinberg LT, Bohl, J, Wharton SB, den Dunnen W, Rub U. Precortical phase of Alzheimer’s disease (AD)-related tau cytoskeletal pathology. Brain Pathol 2016; 26:371-386.

8. Simpson JE, Ince PG, Minett T, Matthews FE, Heath PR, Shaw PJ, Goodall E, Garwood CJ, Ratcliffe LE, Brayne C, Rattray M, Wharton SB, on behalf of the MRC Cognitive Function and Ageing Neuropathology Study Group. Neuronal DNA damage response-associated dysregulation of signalling pathways and cholesterol metabolism at the earliest stages of Alzheimer-type pathology. Neuropathol Appl Neurobiol 2016; 42:167-179.

9. Mathur R, Ince PG, Minett T, Garwood CJ, Shaw PJ, Matthews FE, Brayne C, Simpson JE, Wharton SB. A reduced astrocyte response to -amyloid plaques in the ageing brain associates with cognitive impairment. PLoS ONE 2015 10(2): e0118463. Doi:10.1371/journal.pone.0118463.

10. Simpson JE, Ince PG, Matthews FE, Shaw PJ, Heath PR, Brayne C, Garwood C, Higginbottom A, Wharton SB, on behalf of the MRC Cognitive Function and Ageing Neuropathology Study Group. A neuronal DNA damage response is detected at the earliest stages of Alzheimer’s neuropathology and correlates with cognitive impairment in the MRC-CFAS ageing brain cohort. Neuropathol Appl Neurobiol 2015; 41:483-496.

11. Al-Mashhadi S, Simpson JE, Heath PR, Dickman M, Forster G, Matthews FE, Brayne C, Ince PG,Wharton SB; Medical Research Council Cognitive Function and Ageing Study. Oxidative glial cell damage associated with white matter lesions in the aging human brain. Brain Pathol 2015; 25:565-574.

12. Cooper-Knock J, Walsh MJ, Higginbottom A, Highley JR, Dickman MJ, Edbauer D, Ince PG, Wharton SB, Wilson SA, Kirby J, Hautbergue GM, Shaw PJ. Sequestration of multiple RNA recognition motif-containing proteins by C9orf72 repeat expansions. Brain 2014; 137:2040-2051.

13. Garwood CJ, Simpson JE, Al Mashhadi S, Axe C, Wilson S, Heath PR, Shaw PJ, Matthews FE, Brayne C, Ince PG, Wharton SB, MRC Cogntive Function and Ageing Study. DNA damage response and senescence in endothelial cells of human cerebral cortex and relation to Alzheimer’s neuropathology progression: a population-based study in the MRC-CFAS cohort. Neuropathol Appl Neurobiol 2014; 40:802-814.

14. Highley JR, Kirby J, Jansweijer JA, Webb PS, Hewamadduma CA, Heath PR, Higginbottom A, Raman R, Ferraiuolo L, Cooper-Knock J, McDermott CJ, Wharton SB, Shaw PJ, Ince PG. Loss of nuclear TDP-43 in ALS causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurons. Neuropathol Appl Neurobiol 2014; 40:670-685.

15. Janaway BM, Simpson JE, Hoggard N, Highley JR, Forster G, Drew D, Gebril OH, Matthews FE, Brayne C, Wharton SB, Ince PG. Brain haemosiderin in older people: pathological evidence for an ischaemic origin of MRI microbleeds. Neuropathol Appl Neurobiol 2014; 40:258-269.

16. 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.

17. 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.

18. 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

19. 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.

20. 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.

21. Cooper-Knock J, Hewitt C, Highley JR, Brockington A, Milano A, Man S, Martindale J, Hartley J, Walsh T, Gelsthorpe C, Baxter L, Forster G, Fox , Bury J, Mok K, McDermott CJ, Traynor BJ, Kirby J, Wharton SB, Ince PG, Hardy J, Shaw PJ. Clinico-pathological features in amyotrophic lateral sclerosis with expansions in C9ORF72. Brain 2012; 135:751-64.

22. Keage HA, Ince PG, Matthews FE, Wharton SB, McKeith IG, Brayne C, MRC CFAS and CC75C. Impact of less common and “disregarded” pathologies on dementia burden in a population-based cohort. J Alzheimers Dis 2012; 28:486-93.

23. 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.

24. 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.

25. 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

26. 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.

27. 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.

28. 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.

29. 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.

30. 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
31. 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.

31. 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.

32. Simpson JE, El-Sayed OH, Wharton SB, Heath PR, Holden H, Fernando MS, Matthews F, Forster G, O’Brien JT, Barber R, Kalaria RN, Brayne C, Shaw PJ, Lewis CE, Ince PG on behalf of the MRC Cognitive Function and Ageing Neuropathology Study Group. Microarray expression analysis of cerebral white matter lesions reveals changes in multiple functional pathways. Stroke 2009; 40:369-375.

33. 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.

34. Simpson JE, Ince PG, Higham CE, Gelsthorpe CH, Fernando MS, Matthews F, Forster G, O’Brien JT, Barber R, Kalaria RN, Brayne C, Shaw PJ, Stoeber K, Williams GH, Lewis, CE, Wharton SB, on behalf of the MRC Cognitive Function and Ageing Neuropathology Study Group. Microglial activation in white matter lesions and nonlesional white matter of ageing brains. Neuropathol Appl Neurobiol 2007; 33:670-683.

35. Simpson JE, Fernando MS, Clark L, Ince PG, Matthews F, Forster G, O’Brien JT, Barber R, Kalaria RN, Brayne C, Shaw PJ, Lewis CE, Wharton SB, MRC-CFAS. White matter lesions in an unselected cohort of the elderly: astrocytic, microglial and oligodendrocyte precursor cell responses. Neuropathol Appl Neurobiol 2007; 33:410-419.