Professor Stephen B Wharton

Department of Neuroscience

Professor and Honorary Consultant in Neuropathology

s.wharton@sheffield.ac.uk

Full contact details

Professor Stephen B Wharton
Department of Neuroscience
385a Glossop Road
Sheffield
S10 2HQ
Profile
  • 2014 - present: Professor in Neuropathology, Sheffield University
  • 2001-2014:  Senior Lecturer / Reader in Neuropathology, Sheffield University
  • 1997 - 2001: 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
Research interests

Professor Wharton’s research interest are focused on the cellular and molecular pathology of dementia and brain ageing. His major areas of interest are in:

  • Understanding the pathological basis of dementia through the Cognitive Function and Ageing Study (www.cfas.ac.uk) 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.

External collaborations

  • Prof Fiona Matthews (University of Newcastle) and Prof Carol Brayne (University of Cambridge). The Cognitive Function and Ageing Study.
  • Prof Raj Kalaria (University of Newcastle). Post-stroke dementia.
Publications

Journal articles

Chapters

Conference proceedings papers

  • Hicks D, Rafiee G, Schwalbe E, Howell C, Lindsey J, Hill R, Smith A, Adidharma P, Steel C, Pease L , Crosier S et al (2019) The Molecular Landscape and Clinical Experience in Infant Medulloblastoma. PEDIATRIC BLOOD & CANCER, Vol. 66 (pp S4-S4) RIS download Bibtex download
  • Hicks D, Rafiee G, Schwalbe EC, Lindsey JC, Hill RM, Smith A, Crosier S, Joshi A, Robson K, Wharton S , Jacques T et al (2018) SUBGROUP-DIRECTED CLINICAL AND MOLECULAR STRATIFICATION OF DISEASE RISK IN INFANT MEDULLOBLASTOMA. NEURO-ONCOLOGY, Vol. 20 (pp 123-123) RIS download Bibtex download
  • Seehra RS, Wharton S, Heath P, Ince P, Muthana M, Garwood C & Simpson J (2018) Hypoxia-induced changes in astrocytes and their role in the formation of age-associated white matter lesions. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 44 (pp 17-18) RIS download Bibtex download
  • Chambers A, Minett T, Matthews F, Brayne C, Ince P, Shaw P, Heath P, Simpson J & Wharton S (2018) Advanced glycosylated end products in the ageing brain. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 44 (pp 12-12) RIS download Bibtex download
  • Leach V, Goodall E, Cooper-Knock J, Wang J, Simpson J, Baker D, Drew D, Saffrey J, Romero I, Heath P & Wharton S (2018) Identification of miRNA and mRNA regulatory networks in the ageing blood-brain barrier: Comparative gene expression studies in human and mouse. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 44 (pp 36-36) RIS download Bibtex download
  • Eagle D, Merla A, Ushewokunze SO, Jellinek D, Zaki H, Wharton S & Mckevitt F (2018) Genomic Analysis, Surgical Treatment and Outcomes of Lower-Grade Gliomas in a Single Institution. Neuro-Oncology, Vol. 20(suppl_1) (pp i20-i20) RIS download Bibtex download
  • Eagle D, Merla A, McKevitt F, Clenton S, Bridgewater C, Wharton S, Zaki H, Jellinek D & Ushewokunze S (2017) GENOMIC ANALYSIS, SURGICAL TREATMENT AND OUTCOMES OF LOWER-GRADE GLIOMAS IN A SINGLE INSTITUTION. NEURO-ONCOLOGY, Vol. 19 (pp 238-238) RIS download Bibtex download
  • Hill R, Richardson S, Lindsey J, Crosier S, Schwalbe E, Hicks D, Rafiee G, Smith A, Joshi A, Robson K , Wharton S et al (2017) Time, Pattern and Outcome of Medulloblastoma Relapse is Biology and Therapy-Dependent. PEDIATRIC BLOOD & CANCER, Vol. 64 (pp S13-S14) RIS download Bibtex download
  • Hicks D, Rafiee G, Schwalbe EC, Howell CI, Lindsey JC, Hill RM, Smith A, Crosier S, Joshi A, Robson K , Wharton S et al (2017) SUBGROUP-DIRECTED STRATIFICATION OF DISEASE RISK IN INFANT MEDULLOBLASTOMA. NEURO-ONCOLOGY, Vol. 19 (pp 39-39) RIS download Bibtex download
  • Hill R, Richardson S, Lindsey J, Crosier S, Schwalbe E, Hicks D, Rafiee G, Smithh A, Joshi A, Robson K , Wharton S et al (2017) TIME, PATTERN AND OUTCOME OF MEDULLOBLASTOMA RELAPSE IS BIOLOGY AND THERAPY-DEPENDENT. NEURO-ONCOLOGY, Vol. 19 (pp 41-41) RIS download Bibtex download
  • Vazquez-Villasenor I, Simpson JE, Garwood CJ, Ince PG, Heath PR & Wharton SB (2017) Neuronal senescence as a contributor to neurodegeneration. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 43 (pp 43-43) RIS download Bibtex download
  • Ameen-Ali KE, Simpson JE, Wharton SB, Heath PR, Sharp P & Berwick J (2017) Early cellular changes and cognitive decline in an Alzheimer's mouse model. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 43 (pp 42-43) RIS download Bibtex download
  • Crosier S, Hicks D, Schwalbe E, Williamson D, Nicholson S, Michalski A, Pizer B, Bailey S, Bown N, Robson K , Wharton S et al (2016) CENTRALISED MOLECULAR PATHOLOGY FOR RARE TUMOURS: A NATIONAL FEASIBILITY STUDY OF REAL-TIME MEDULLOBLASTOMA DIAGNOSTICS. NEURO-ONCOLOGY, Vol. 18 (pp 115-115) RIS download Bibtex download
  • Hicks D, Rafiee G, Schwalbe E, Howell C, Lindsey J, Hill R, Smith A, Crosier S, Joshi A, Robson K , Wharton S et al (2016) SUBGROUP-DIRECTED STRATIFICATION OF RISK IN INFANT MEDULLOBLASTOMA. NEURO-ONCOLOGY, Vol. 18 (pp 111-111) RIS download Bibtex download
  • Ratcliffe L, Garwood CJ, Heath P, Villasenor I, Simpson J, Ince PG & Wharton SB (2016) Impairment of IGF1 signalling in human astrocytes and it's effect on astrocyte support for neurons. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 42 (pp 51-52) RIS download Bibtex download
  • Vazquez-Villasenor I, Simpson JE, Garwood C, Ince PG, Heath P & Wharton SB (2016) Neuronal senescence as a contributor to neurodegeneration. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 42 (pp 27-28) RIS download Bibtex download
  • Clifford SC, Crosier S, Hicks D, Nicholson S, Robson K, Jacques TS, Wharton S, Bown N, Michalski A & Pizer B (2016) Establishment of national real-time central pathology review (CPR) and molecular diagnostics for medulloblastoma (MB). NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 42 (pp 19-20) RIS download Bibtex download
  • Ince PG, Minett T, Forster G & Wharton SB (2015) Microinfarcts, Small Vessel Disease and Dementia in the population-representative CFAS brain donor cohort. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 41 (pp 22-23) RIS download Bibtex download
  • Mathur R, Ince PG, Minett T, Garwood CJ, Shaw PJ, Matthews FE, Brayne C, Simpson JE, Wharton SB & Ageing MRCCF (2015) A reduced astrocyte response to beta-amyloid plaques in the ageing brain associates with dementia and cognitive impairment. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 41 (pp 30-31) View this article in WRRO RIS download Bibtex download
  • Vazquez-Villasenor I, Simpson JE, Garwood C, Ince PG, Heath P & Wharton SB (2015) Neuronal senescence as a contributor to neurodegeneration. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 41 (pp 32-32) RIS download Bibtex download
  • Hill RM, Kuijper S, Lindsey J, Schwalbe EC, Barker K, Boult J, Williamson D, Ahmad Z, Hallsworth A, Ryan S , Poon E et al (2014) Abstract LB-201: MYC and TP53 defects interact at medulloblastoma relapse to define rapidly progressive disease and can be targeted therapeutically. Tumor Biology RIS download Bibtex download
  • Beer A, Cooper-Knock J, Higginbottom A, Robin Highley J, Wharton SP, Milano A, Jones A, Al-Chalabi A, Kirby J & Shaw PJ (2014) AMYOTROPHIC LATERAL SCLEROSIS ASSOCIATED WITH AN INTERMEDIATE LENGTH GGGGCC REPEAT EXPANSION HAS DISTINCT NEUROPATHOLOGY COMPARED TO PATIENTS WITH LARGER EXPANSIONS. Journal of Neurology, Neurosurgery & Psychiatry, Vol. 85(10) (pp e4.130-e4) RIS download Bibtex download
  • Al-Mashhadi SA, Simpson JE, Heath PR, Dickman MJ, Ince PG & Wharton SB (2014) Oxidative stress and DNA damage in cerebral white matter lesions of the ageing human brain. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 40 (pp 33-34) RIS download Bibtex download
  • Simpson JE, Ince PG, Matthews F, Shaw PJ, Heath PR, Brayne C, Garwood C, Abdalla H, Higginbottom A & Wharton SB (2014) A neuronal DNA damage response is detected at low Braak stages and correlates with cognitive impairment in the ageing brain. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 40 (pp 31-32) RIS download Bibtex download
  • Highley JR, Cooper-Knock J, Frolov A, Charlesworth G, Kirby J, Wharton SB, Ince PG, Shaw PJ, Wood N & Bandman O (2013) A pathological basis for the association of parkinsonism and amyotrophic lateral sclerosis. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 39 (pp 51-51) RIS download Bibtex download
  • Clifford S, Crosier S, Nicholson S, Robson K, Jacques T, Wharton S, Bown N, Michalski A & Pizer B (2013) A national feasibility study of real-time central pathology review (CPR) and molecular diagnostics for medulloblastoma. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 39 (pp 20-20) RIS download Bibtex download
  • Al-Mashhadi SA, Simpson JE, Heath PR, Dickman MJ, Ince PG & Wharton SB (2013) Oxidative stress and DNA damage in cerebral white matter lesions of the ageing human brain. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 39 (pp 36-37) RIS download Bibtex download
  • Ince PG, Janaway B, Wharton SB, Simpson JE, Highley JR, Matthews FE, Forster G & Brayne C (2013) Evidence for an ischemic origin of deep brain 'microbleeds'. CEREBROVASCULAR DISEASES, Vol. 35 (pp 42-42) RIS download Bibtex download
  • Waller R, Heath PR, Woodroofe MN, Francese S, Wharton SB, Ince PG, Sharrack B & Simpson JE (2012) Microarray analysis of the astrocyte transcriptome in normal appearing white matter in multiple sclerosis. JOURNAL OF NEUROIMMUNOLOGY, Vol. 253(1-2) (pp 54-54) RIS download Bibtex download
  • Crosier S, Nicholson SL, Robson K, Jacques T, Wharton S, Bown N, Michalski A, Pizer B & Clifford S (2012) A NATIONAL FEASIBILITY STUDY OF REAL-TIME CENTRAL PATHOLOGY REVIEW AND MOLECULAR DIAGNOSTICS FOR MEDULLOBLASTOMA. NEURO-ONCOLOGY, Vol. 14 (pp 44-44) RIS download Bibtex download
  • Brockington A, Ning K, Heath P, Wood E, Malik K, Fusi N, Wharton S, Ince PG & Shaw PJ (2012) MOTOR NEURONES SUBTYPES RESISTANT TO DEGENERATION IN AMYOTROPHIC LATERAL SCLEROSIS SHOW DISTINCT SYNAPTIC CHARACTERISTICS ACROSS SPECIES. JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol. 83(3) RIS download Bibtex download
  • Romanowski CA, Hoggard N, Jellinek DA, Clenton S, McKevitt F, Wharton S, Craven I, Buller A, Waddle C, Bigley J , Wilkinson ID et al (2011) SEMI-AUTOMATED VOLUMETRIC ANALYSIS OF LOW-GRADE GLIOMAS. NEURO-ONCOLOGY, Vol. 13 (pp 140-140) RIS download Bibtex download
  • Simpson J, Richardson K, Heath P & Wharton S (2011) Oxidative nucleic acid damage in motor neuron disease. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 37 (pp 36-36) RIS download Bibtex download
  • Nicholson SL, Robson DK, Wharton SB, Jacques TS, Michalski AM, Pizer B, Bown NP & Clifford SC (2011) A feasibility study of real-time central pathology review (CPR) and molecular diagnostics for medulloblastoma in the United Kingdom. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 37 (pp 18-19) RIS download Bibtex download
  • Simpson JE, Ince PG, Heath PR, Raman R, Shaw PJ, Gelsthorpe C, Baxter L, Forster G, Matthews F, Savva G , Brayne C et al (2011) Microarray analysis of the astrocyte transcriptome in the ageing brain: relationship to Alzheimer's pathology and ApoE genotype. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 37 (pp 33-33) RIS download Bibtex download
  • Rashbass J, Collins VP & Wharton SB (2011) The development of the National Brain and CNS Tumour Registry. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 37 (pp 19-19) RIS download Bibtex download
  • Simpson J, Ince P, Heath P, Raman R, Shaw P, Gelsthorpe C, Baxter L, Forster G, Matthews F, Savva G , Brayne C et al (2010) Microarray analysis of the astrocyte transcriptome in the ageing brain: relationship to Alzheimer's pathology and ApoE genotype. BRAIN PATHOLOGY, Vol. 20 (pp 46-46) RIS download Bibtex download
  • Nicholson S, Robson D, Jacques T, Wharton S, Michalski A, Pizer B, Bown N & Clifford S (2010) ESTABLISHMENT OF REAL-TIME CENTRALISED PATHOLOGY REVIEW (CPR) AND MOLECULAR DIAGNOSTICS FOR MEDULLOBLASTOMA IN THE UNITED KINGDOM. NEURO-ONCOLOGY, Vol. 12 (pp 6-6) RIS download Bibtex download
  • Nicholson SL, Robson K, Jaques T, Wharton SB, Michalski A, Pizer B, Bown N & Clifford SC (2010) ESTABLISHMENT OF REAL-TIME CENTRALISED PATHOLOGY REVIEW (CPR) AND MOLECULAR DIAGNOSTICS FOR MEDULLOBLASTOMA IN THE UNITED KINGDOM. NEURO-ONCOLOGY, Vol. 12(6) (pp II58-II58) RIS download Bibtex download
  • Langheinrich T, Romanowski C, Wharton S & Hadjivassiliou M (2010) Presenilin 1 S170P Mutation with a Limbic Encephalitis like Presentation. NEUROLOGY, Vol. 74(9) (pp A244-A244) RIS download Bibtex download
  • Langheinrich TC, Wharton S, Romanowski CAJ & Hadjivassiliou M (2009) BIOPSY PROVEN ATAXIC VARIANT EARLY ONSET ALZHEIMER'S DISEASE WITH A LIMBIC ENCEPHALITIS LIKE PRESENTATION. JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol. 80(11) RIS download Bibtex download
  • Simpson JE, Ince PG, Theaker R, Haynes L, Forster G, Shaw PJ, Matthews F, Savva G, Brayne C, Wharton SB & MRC Cognitive Function & Ageing Ne (2009) Evidence of an astrocytic DNA damage response to oxidative stress in the ageing brain. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 35 (pp 18-19) RIS download Bibtex download
  • Lace G, Forster G, Savva G, Matthews F, Brayne C, De Silva R, Strong MJ, Ince PG & Wharton SB (2009) Variation in 4R and 3R tau isoforms in the ageing population. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 35 (pp 19-19) RIS download Bibtex download
  • Alafuzoff I, Al-Sarraj S, Arzberger T, Bodi I, Bogdanovic N, Budka H, Bugiani O, Boluda S, Duyckaerts C, Ferrer I , Gelpi E et al (2009) Reproducibility in the assessment of Alzheimer's disease and Lewy body disease-related pathologies: a study by Brain Net Europe. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 35 (pp 12-13) RIS download Bibtex download
  • Simpson J, Ince P, Theaker R, Haynes L, Forster G, Shaw P, Matthews F, Savva G, Brayne C & Wharton S (2008) DNA oxidative damage and repair mechanisms in astrocytes, and their relationship to Alzheimer-type pathology in the ageing brain. JOURNAL OF NEURAL TRANSMISSION, Vol. 115(12) (pp 1727-1727) RIS download Bibtex download
  • Lace GL, Savva G, Strong M, Ince PG, Forster G, Matthews F, Brayne C & Wharton SB (2008) Variation in 4R and 3R Tau isoforms in the ageing population. JOURNAL OF NEURAL TRANSMISSION, Vol. 115(12) (pp 1725-1726) RIS download Bibtex download
  • Harkness KAC, Langeinrich T & Wharton SB (2008) Optic neuropathy and cerebellar degeneration. JOURNAL OF NEUROIMMUNOLOGY, Vol. 197(2) (pp 175-175) RIS download Bibtex download
  • Simpson JE, Ince PG, Lace G, Forster G, Shaw PJ, Matthews F, Brayne C, Wharton SB & MRC Cognitive Function Ageing (2008) Characterisation of astrocytes in relation to Alzheimer-type pathology in the ageing brain using a population-based neuropathology cohort. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 34 (pp 31-31) RIS download Bibtex download
  • Wharton SB, Savva G, Ince PG, Matthews F, Brayne C & MRC-CFAS (2008) Age effects on the relationship between pathology and cognitive impairment in a population cohort. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 34 (pp 10-10) RIS download Bibtex download
  • Lace G, Forster G, Savva G, Barclay JJ, Dakin L, Matthews F, Brayne C, De Silva R, Ince PG, Wharton SB & MRC-CFAS (2008) Population variation in tau pathology in the MRC-CFAS neuropathology cohort. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 34 (pp 10-11) RIS download Bibtex download
  • Simpson JE, El-Sayed OH, Wharton SB, Heath P, Holden H, Forster G, Fernando MS, Matthews F, Brayne C, Lewis CE , Barber R et al (2008) Microarray gene expression analysis of deep subcortical lesions in the ageing brain reveals changes in multiple functional pathways. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 34 (pp 30-31) RIS download Bibtex download
  • Lace G, Ince PG, Matthews F, Brayne C, De Silva R & Wharton SB (2007) Population variation in tau pathology in the aged hippocampus in the MRC-CFAS neuropathology cohort. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 33(2) (pp 263-263) RIS download Bibtex download
  • Highley JR, Smith O, Brockington A, Kirby J, Wharton SB, Spillantini M, Lowe JS, Layfield R, Shaw PJ & Ince PG (2007) Extra-motor manifestations of motor neurone disease and the role of TDP43 in ALS variants. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 33(2) (pp 264-265) RIS download Bibtex download
  • Hosny O, Highley JR, Simpson JE, Forster G, Wharton SB & Ince PG (2007) Axonal number and myelin sheath degeneration in MRI hyperintense white matter lesions in the aging brain. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 33(2) (pp 266-267) RIS download Bibtex download
  • Simpson JE, El-Sayed OH, Wharton SB, Heath P, Holden H, Forster G, Fernando MS, Matthews F, Brayne C, Lewis CE , Barber R et al (2007) Microarray gene expression profiling of deep subcortical lesions in the ageing brain. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 33(2) (pp 254-255) RIS download Bibtex download
  • Simpson JE, Higham CE, Gelsthorpe CH, Fernando MS, Matthews F, Forster G, O'Brien JT, Barber R, Kalaria RN, Brayne C , Shaw PJ et al (2007) Microglial activation in white matter of the ageing brain. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 33(2) (pp 255-255) RIS download Bibtex download
  • Jellinek DA, Levy D, Maltby E, Atkey N, Hibberd S, Crimmins D, Stoeber K, Williams GH & Wharton SB (2006) Cytogenetic subtypes of oligodendroglioma differ in their apoptotic index, while the population of replication-licensed, non-proliferating cells is higher in anaplastic tumors but does not differ according to 1p,19q status. NEURO-ONCOLOGY, Vol. 8(4) (pp 459-459) RIS download Bibtex download
  • Atkey N, Wharton SB, Jellinek D & Maltby EL (2006) FISH for the detection of 1p and 19q deletions in oligodendrogioma paraffin wax sections - A retrospective study of 55 cases. JOURNAL OF MEDICAL GENETICS, Vol. 43 (pp S101-S101) RIS download Bibtex download
  • Ince PG, Fernando MS, Matthews F, Brayne C, Wharton SB, O'Brien JT, Lewis C, Kalaria RN, Shaw PJ & Simpson J (2006) Molecular markers of tissue hypoxia and glial pathology associated with incidental white matter lesions in the ageing brain. BRAIN PATHOLOGY, Vol. 16 (pp S92-S92) RIS download Bibtex download
  • Ince PG, Brayne C, Matthews F, Chatfield M, Esiri MM, Lowe JS & Wharton SB (2006) New pathological findings from the MRC-cognitive function and ageing study (CFAS) neuropathology cohort. BRAIN PATHOLOGY, Vol. 16 (pp S127-S127) RIS download Bibtex download
  • Simpson JE, Fernando MS, Matthews F, Brayne C, Lewis CE, Barber R, Kalaria RN, Forster G, Esteves F, Wharton SB , Shaw PJ et al (2006) Molecular markers of tissue hypoxia are associated with deep subcortical white matter lesions in the ageing brain. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 32(2) (pp 224-224) RIS download Bibtex download
  • Simpson JE, Fernando MS, Clark L, Ince PG, Matthews F, Forster G, O'Brien JT, Barber R, Kalaria RN, Brayne C , Shaw PJ et al (2006) Glial cell pathology of periventricular and deep white matter lesions in the ageing brain. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 32(2) (pp 224-225) RIS download Bibtex download
  • Owasil R, O’Neill R, Keable A, Nimmo J, MacGregor Sharp M, Kelly L, Saito S, Simpson JE, Weller RO, Smith C , Attems J et al () The Pattern of AQP4 Expression in the Ageing Human Brain and in Cerebral Amyloid Angiopathy. International Journal of Molecular Sciences, Vol. 21(4) (pp 1225-1225) RIS download Bibtex download

Datasets

Research group

Current PhD students:

  • Hemant Mistry
  • Monica Gaugnelli
  • Martyna Matuszyk

Research team:

  • Dr Rachel Waller
  • Dr Irina Vacquez Villasenor
Grants

Current funding sources

  • Alzheimer’s Society
  • Alzheimer’s Research UK
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

  • Member of the Alzheimer’s Research UK Grant Review Board 2016-
  • Chief of panel of examiners in neuropathology for the Royal College of Pathologists (2018-)
  • Examiner in neuropathology for the Royal College of Pathologists (2005-)
  • Member British Neuropathological Society Academic Affairs Committee (2018-).

Membership of associations and societies - current

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

Defective nutrient signalling and dementia: an epidemiological neuropathology approach. 

Funded by the Alzheimer’s Society, this project examines the effects of diabetes on the brain. Diabetes is a major risk factor for dementia and Alzheimer’s disease, but the mechanisms by which it contributes to cognitive decline are unclear.

We seek to define the contribution of diabetes and related metabolic changes to dementia, and to identify novel mechanisms by which it damages different key cell types within the brain; the nerve cells, the cells that line brain blood vessels and the astrocyte, which supports and integrates the functions of the other two types.

Using autopsy-brain samples from the Cognitive Function and Ageing Study (CFAS), we plan to investigate the relationship of diabetes to dementia and to Alzheimer’s pathology and vascular pathology. The CFAS brain-donation cohort, held in Sheffield, is from a population (rather than clinic) based sample of over 65yr olds; its unselected nature means that it is ideal for examining interactions between pathologies and relationships to dementia in an unbiased way.

Cells in the brain and elsewhere are able to sense changes to nutrients, such as glucose, with specialised signalling pathways. Alterations in these pathways may impair the ability of nerve cells to function, so we are examining the impact of diabetes on them.

We use methods that allow us to examine overall changes in the activities of genes in cells to identify new mechanisms by which diabetes impairs different brain cell-types. Obesity and diabetes are increasing problems. This proposal will better define how they contribute to dementia.

Neuronal Senescence as a Contributory Mechanism to Dementia

Funded by Alzheimer's Research UK, this project aims to study the contribution of neuronal senescence to dementia. Markers of dementia, such as tangles and plaques that characterise Alzheimer’s, do not explain all dementia, and treatments aimed at them have been unsuccessful. This suggests other processes contribute to dementia.

Senescent cells, sometimes called zombie cells, are persistently damaged cells, often because of damage to their DNA, which carries all the instructions for the cell. These cells remain alive, but they do not carry out their normal functions. Additionally, they produce factors that damage nearby cells and cause inflammation. Zombie cells are described in other tissues and diseases, and there are drug treatments aimed at them. However, their role in dementia is not understood. Using brain tissue samples from the Cognitive Function and Ageing Study, we plan to identify senescent nerve cells in the brain and determine how they relate to dementia.

To determine how senescence causes damage, we will isolate nerve cells with and without markers of senescence from the same cases, and investigate effects on the cells by determining differences in the gene messages present. This will provide greater understanding of how senescence contributes to dementia and identify specific ways in which senescence affects nerve cells, which may lead us to new approaches to target zombie cells.

A Cellular Pathology and Gene Expression Approach to Understand the Basis of Progressive Dementia Occurring After Stroke. 

This work is funded by the Alzheimer’s Society and is a collaboration with Prof Kalaria at the University of Newcastle. Around a quarter of stroke survivors develop progressive dementia after more than 3-6 months, and with more stroke survivors, post stroke dementia is an increasing problem. We aim to identify cell mechanisms that can cause post-stroke dementia.

We are using brain tissue donated to the Cognitive Function After Stroke Study (CogFAST), which includes individuals with and without dementia after stroke. Previous work showed that the front of the brain is particularly affected, with leakiness of small blood vessels in the white matter. This can damage the processes or wires of nerve cells that pass through this area.

We are isolating different cell types in this area and using methods to examine changes in the patterns of gene expression in these cells. This has the potential to identify new mechanisms that contribute to a stroke survivor developing dementia, and which might lead to new treatments.

Cholesterol Dysregulation in the Neurovascular Unit as an Early Contributor to Neuronal Dysfunction in Alzheimer’s Disease. 

This is a PhD studentship funded by Alzheimer’s Research UK.

Variation in Astrocyte Responses to Different Molecular Pathologies and the Effect on Neuroprotection.

This is a PhD studentship funded by the Alzheimer’s Society.

The Effects of Systemic Atherosclerosis on the Brain Neurovascular Unit. 

A collaboration with Prof Sheila Francis in Cardiovascular Sciences, this PhD studentship is funded by Consejo Nacional de Ciencia y Tecnología (CONACYT), Mexico

Additional Collaborations.

Work on the role of neuroinflammation in dementia, with Dr Julie Simpson, and on Gene Based Therapies for Frontotemporal dementia (ARUK-funded) with Prof Mimoun Azzouz.