Dr Robin Highley
DPhil, FRCPath
Neuroscience, School of Medicine and Population Health
Senior Clinical Lecturer in Neuropathology
robin.highley@sheffield.ac.uk
+44 114 222 2244
+44 114 222 2244
44 114 222 2290
(fax)
Room B28, Sheffield Institute for Translational Neuroscience (SITraN)
Full contact details
Dr Robin Highley
Neuroscience, School of Medicine and Population Health
Room B28
Sheffield Institute for Translational Neuroscience (SITraN)
385a Glossop Road
Sheffield
S10 2HQ
Neuroscience, School of Medicine and Population Health
Room B28
Sheffield Institute for Translational Neuroscience (SITraN)
385a Glossop Road
Sheffield
S10 2HQ
- Profile
-
I graduated in Experimental Psychology from the University of Oxford in 1993 and subsequently completed a DPhil in Oxford studying the neuropathology of Schizophrenia from which I completed in 1997.
I then trained in medicine at the University of Birmingham from 1997-2002. Following this, I moved to Sheffield, to train in neuropathology, gaining the European Fellowship of Neuropathology in 2008 and FRCPath in 2009.
On completing this training in 2009, I took up an MRC/Motor Neurone Disease Association Lady Edith Wolfson Fellowship to study Motor neurone disease. I became a Senior Clinical Lecturer in Neuropathology in 2012.
I also work as a Consultant Neuropathologist for the South and East Yorkshire Neuropathology Network, which provides diagnostic neuropathology services to the Sheffield Teaching Hospitals NHS Foundation Trust and the Hull and East Yorkshire NHS Trust.
- Research interests
-
I am interested in the neuropathology and pathophysiology of neurodegeneration, in particular motor neurone disease (MND), Parkinson’s disease and dementia.
I use standard neuropathological techniques to characterise post mortem tissue kindly donated by individuals with these diseases and to highlight contrasts with tissue from people who were free from disease. These methods are used to study genes, proteins and molecular pathways of interest and the pathological effects of gene mutations known to neurodegeneration.
I study mouse, zebrafish and cellular models of disease and the comparison of these with human tissue based pathology.
Current projects
- The pathobiology and neuropathology of C9ORF72-mediated MND
- Oligodendrocyte disease and function in MND
- TIGAR-related pathology in Parkinson’s disease
- Zebrafish models of Parkinson’s disease
- The relationship between pathological and radiological measures of white matter in vascular dementia.
- Publications
-
Journal articles
- A Y374X TDP43 truncation leads to an altered metabolic profile in amyotrophic lateral sclerosis fibroblasts driven by pyruvate and TCA cycle intermediate alterations. Frontiers in Aging Neuroscience, 15. View this article in WRRO
- An interaction between synapsin and C9orf72 regulates excitatory synapses and is impaired in ALS/FTD. Acta Neuropathologica.
- Atypical TDP-43 protein expression in an ALS pedigree carrying a p.Y374X truncation mutation in TARDBP. Brain Pathology.
- Tissue microarray (TMA) use in post mortem neuropathology. Journal of Neuroscience Methods.
- Review: Microglia in motor neuron disease. Neuropathology and Applied Neurobiology. View this article in WRRO
- Oligodendrocyte pathology exceeds axonal pathology in white matter in human amyotrophic lateral sclerosis. The Journal of Pathology. View this article in WRRO
- TDP43 proteinopathy is associated with aberrant DNA methylation in human amyotrophic lateral sclerosis. Neuropathology and Applied Neurobiology. View this article in WRRO
- Neuropathological characterisation of a novel TBK1 loss of function mutation associated with amyotrophic lateral sclerosis. Neuropathology & Applied Neurobiology. View this article in WRRO
- Quantitative histomorphometry of capillary microstructure in deep white matter. NeuroImage Clinical, 23. View this article in WRRO
- Histological data of axons, astrocytes, and myelin in deep subcortical white matter populations. Data in Brief, 23. View this article in WRRO
- TIGAR inclusion pathology is specific for Lewy body diseases. Brain Research, 1706, 218-223. View this article in WRRO
- Iba-1-/CD68+ microglia are a prominent feature of age-associated deep subcortical white matter lesions. PLoS ONE, 14(1). View this article in WRRO
- Combined FUS+ Basophilic Inclusion Body Disease and Atypical Tauopathy Presenting with an ALS/MND-plus Phenotype.. Neuropathology and Applied Neurobiology. View this article in WRRO
- ALS-linked FUS mutations confer loss and gain of function in the nucleus by promoting excessive formation of dysfunctional paraspeckles. Acta Neuropathologica Communications, 7. View this article in WRRO
- Case report of intraventricular schwannoma. British Journal of Neurosurgery, 33(1), 96-98.
- Local volume fraction distributions of axons, astrocytes, and myelin in deep subcortical white matter. NeuroImage, 179, 275-287. View this article in WRRO
- Management of elderly patients with glioblastoma-multiforme—a systematic review. The British Journal of Radiology, 91(1088), 20170271-20170271.
- Concomitant idiopathic hypertrophic spinal pachymeningitis and Guillain-Barré syndrome in a patient: coincidence or a triggering mechanism?. Journal of Neurosurgery: Spine, 27(3), 335-340. View this article in WRRO
- Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy. PLOS Genetics, 13(4). View this article in WRRO
- A data-driven approach links microglia to pathology and prognosis in amyotrophic lateral sclerosis.. Acta Neuropathol Commun, 5(1), 23-23. View this article in WRRO
- Spinal muscular atrophy: Factors that modulate motor neurone vulnerability.. Neurobiology of Disease. View this article in WRRO
- Motor neurone disease/amyotrophic lateral sclerosis associated with intermediate‐length CAG repeat expansions in Ataxin‐2 does not have 1C2‐positive polyglutamine inclusions. Neuropathology and Applied Neurobiology, 42(4), 377-389. View this article in WRRO
- Oligogenic inheritance of optineurin (OPTN) and C9ORF72 mutations in ALS highlights localisation of OPTN in the TDP‐43‐negative inclusions of C9ORF72‐ALS. Neuropathology, 36(2), 125-134. View this article in WRRO
- Glucocerebrosidase 1 deficient Danio rerio mirror key pathological aspects of human Gaucher disease and provide evidence of early microglial activation preceding alpha-synuclein-independent neuronal cell death. Human Molecular Genetics, 24(23), 6640-6652. View this article in WRRO
- Antisense RNA foci in the motor neurons of C9ORF72-ALS patients are associated with TDP-43 proteinopathy. Acta Neuropathologica, 130(1), 63-75. View this article in WRRO
- A clinicopathologic study of 11 rosette-forming meningiomas: a rare and potentially confusing pattern. Acta Neuropathologica, 130(2), 311-313.
- C9ORF72 GGGGCC Expanded Repeats Produce Splicing Dysregulation which Correlates with Disease Severity in Amyotrophic Lateral Sclerosis. PLOS ONE, 10(5), e0127376-e0127376. View this article in WRRO
- The Spectrum of C9orf72-mediated Neurodegeneration and Amyotrophic Lateral Sclerosis. Neurotherapeutics, 12(2), 326-339. View this article in WRRO
- Gene expression signatures in motor neurone disease fibroblasts reveal dysregulation of metabolism, hypoxia-response and RNA processing functions.. Neuropathol Appl Neurobiol, 41(2), 201-226. View this article in WRRO
- Gamma-synuclein pathology in amyotrophic lateral sclerosis. Annals of Clinical and Translational Neurology, 2(1), 29-37. View this article in WRRO
- Intermediate length C9orf72 expansion in an ALS patient without classical C9orf72 neuropathology. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 16(3-4), 249-251. View this article in WRRO
- Loss of nuclear TDP-43 in amyotrophic lateral sclerosis (ALS) causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurones.. Neuropathol Appl Neurobiol, 40(6), 670-685.
- Sequestration of multiple RNA recognition motif-containing proteins by C9orf72 repeat expansions.. Brain, 137(Pt 7), 2040-2051. View this article in WRRO
- TDP-43 in the Population: Prevalence and Associations with Dementia and Age.. J Alzheimers Dis.
- GGGGCC Repeat Expansion of C9ORF72 Is Toxic Via Sequestration Of RNA Binding Proteins And Consequent Disruption Of RNA Splicing (S56.004). Neurology, 82(10_supplement).
- GGGGCC Repeat Expansion of C9ORF72 Is Toxic Via Sequestration Of RNA Binding Proteins And Consequent Disruption Of RNA Splicing (1II-2.005). Neurology, 82(10_supplement).
- Axonal Preservation in Deep Subcortical White Matter Lesions in the
Ageing Brain. Journal of Aging Science, 2(1). View this article in WRRO
- TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions.. Acta Neuropathol, 127(3), 407-418. View this article in WRRO
- Brain haemosiderin in older people: pathological evidence for an ischaemic origin of magnetic resonance imaging (MRI) microbleeds.. Neuropathol Appl Neurobiol, 40(3), 258-269. View this article in WRRO
- C9ORF72 expansions, parkinsonism, and Parkinson disease: a clinicopathologic study.. Neurology, 81(9), 808-811.
- Trigeminal neuralgia: no laughing matter. Practical Neurology, 13(4), 263-267.
- Lack of unique neuropathology in amyotrophic lateral sclerosis associated with p.K54E angiogenin (ANG) mutation.. Neuropathol Appl Neurobiol, 39(5), 562-571. View this article in WRRO
- Concurrence of multiple sclerosis and amyotrophic lateral sclerosis in patients with hexanucleotide repeat expansions of C9ORF72.. J Neurol Neurosurg Psychiatry, 84(1), 79-87.
- Clinico-pathological features in amyotrophic lateral sclerosis with expansions in C9ORF72.. Brain, 135(Pt 3), 751-764.
- Molecular pathology and genetic advances in amyotrophic lateral sclerosis: an emerging molecular pathway and the significance of glial pathology.. Acta Neuropathol, 122(6), 657-671.
- Pathological findings in a case of stiff person syndrome with anti-GAD antibodies.. Mov Disord, 26(11), 2138-2139.
- TARDBP mutations, amyotrophic lateral sclerosis and alternative splicing in human fibroblasts. BRAIN PATHOLOGY, 20, 32-32.
- Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis.. Neurogenetics, 11(2), 217-225. View this article in WRRO
- Novel FUS/TLS mutations and pathology in familial and sporadic amyotrophic lateral sclerosis.. Arch Neurol, 67(4), 455-461.
- Antibody-negative neuromyelitis optica with heavy B-cell infiltration.. APMIS, 117(10), 768-772.
- Sulcal variability, stereological measurement and asymmetry of Broca's area on MR images.. J Anat, 211(4), 534-555.
- Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations.. Ann Neurol, 61(5), 427-434.
- ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B). Neurology, 67(6), 1074-1077.
- Size of hippocampal pyramidal neurons in schizophrenia. Psiquiatria Biologica, 11(4), 129-133.
- Size of hippocampal pyramidal neurons in schizophrenia.. Br J Psychiatry, 183, 414-417.
- Sex-dependent effects of schizophrenia: an MRI study of gyral folding, and cortical and white matter volume.. Psychiatry Res, 124(1), 11-23.
- Low medial and lateral right pulvinar volumes in schizophrenia: a postmortem study.. Am J Psychiatry, 160(6), 1177-1179.
- Asymmetry of the uncinate fasciculus: a post-mortem study of normal subjects and patients with schizophrenia.. Cereb Cortex, 12(11), 1218-1224.
- Estimated neuronal populations and volumes of the hippocampus and its subfields in schizophrenia.. Am J Psychiatry, 159(5), 821-828.
- Schizophrenia and the frontal lobes: post-mortem stereological study of tissue volume.. Br J Psychiatry, 178, 337-343.
- Temporal lobe epilepsy with and without psychosis: exploration of hippocampal pathology including that in subpopulations of neurons defined by their content of immunoreactive calcium-binding proteins.. Acta Neuropathol, 99(5), 547-554.
- Anomalous asymmetry of fusiform and parahippocampal gyrus gray matter in schizophrenia: A postmortem study.. Am J Psychiatry, 157(1), 40-47.
- Fiber content of the fornix in schizophrenia: lack of evidence for a primary limbic encephalopathy.. Am J Psychiatry, 156(11), 1720-1724.
- Schizophrenia and temporal lobe asymmetry. A post-mortem stereological study of tissue volume.. Br J Psychiatry, 175, 127-134.
- The size and fiber composition of the anterior commissure with respect to gender and schizophrenia.. Biol Psychiatry, 45(9), 1120-1127.
- The size and fibre composition of the corpus callosum with respect to gender and schizophrenia: a post-mortem study.. Brain, 122 ( Pt 1), 99-110.
- Anomalies of cerebral asymmetry in schizophrenia interact with gender and age of onset: a post-mortem study.. Schizophr Res, 34(1-2), 13-25.
- Temporal-lobe length is reduced, and gyral folding is increased in schizophrenia: a post-mortem study.. Schizophr Res, 34(1-2), 1-12.
- A validation of MRI cortical surface rendering of the human post-mortem brain. SCHIZOPHR RES, 29(1-2), 87-87.
- A stereological study of the volume of the hippocampus in postmortem control and schizophrenic brains. SCHIZOPHR RES, 29(1-2), 88-88.
- The anatomy of the fornix and schizophrenia: A postmortem study. SCHIZOPHR RES, 29(1-2), 70-70.
- A postmortem study of the size and asymmetry of the parahippocampal and fusiform gyrii in schizophrenia. SCHIZOPHR RES, 29(1-2), 71-71.
- Molecular determinants of protein pathogenicity at the single-aggregate level. Advanced Science.
- Pre-clinical development of AP4B1 gene replacement therapy for hereditary spastic paraplegia type 47. EMBO Molecular Medicine.
- Proteinopathies as Hallmarks of Impaired Gene Expression, Proteostasis and Mitochondrial Function in Amyotrophic Lateral Sclerosis. Frontiers in Neuroscience, 15.
Chapters
- Motor neuron disorders, Greenfield's Neuropathology 10e Set (pp. 875-906). CRC Press
- Neuropathology and muscle biopsy techniques, Bancroft's Theory and Practice of Histological Techniques (pp. 306-336). Elsevier
- Motor neuron disorders In Love S, Budka H, Ironside JW & Perry A (Ed.), Greenfield's Neuropathology (pp. 817-848). Boca Raton: CRC Press.
- Techniques in neuropathology, Bancroft's Theory and Practice of Histological Techniques (pp. 353-380). Elsevier
- List of contributors, Bancroft's Theory and Practice of Histological Techniques (pp. xiii-xiv). Elsevier
- Techniques in neuropathology In Suvarna KS, Layton C & Bancroft JD (Ed.), Theory and Practice of Histological Techniques (pp. 352-380). Churchill Livingstone
- The neuropathology of the motor neurone diseases In Strong MJ (Ed.), Amyotrophic Lateral Sclerosis and the Frontotemporal Dementias OUP Oxford
- Amyotrophic Lateral Sclerosis and the Frontotemporal Dementias In Strong MJ (Ed.), Amyotrophic Lateral Sclerosis and the Frontotemporal Dementias OUP Oxford
- Techniques in neuropathology, Bancrofts Theory and Practice of Histological Techniques E-Book (pp. 353-380).
Conference proceedings papers
- Inflammatory pathology in human motor neuron disease. JOURNAL OF PATHOLOGY, Vol. 261 (pp S5-S5)
- Tissue Microarray (TMA) Use in Post Mortem Neuropathology. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 46 (pp 46-46)
- DNA Methylation in Amyotrophic Lateral Sclerosis. JOURNAL OF PATHOLOGY, Vol. 249 (pp S15-S15)
- Iba-1-/CD68+microglia are a prominent feature of age-associated deep subcortical white matter lesions. Neuropathology and Applied Neurobiology, Vol. 45(S1) (pp 33-33), 6 March 2019 - 8 March 2019. View this article in WRRO
- Nottingham Pathology 2016. 9th Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland, 28 June - 1 July 2016. The Journal of Pathology, Vol. 240 (pp S1-S48) View this article in WRRO
- Investigating the mechanisms underlying oligodendrocyte dysfunction in C9ORF72 ALS. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 42(S1) (pp 28-28), 2 March 2016 - 4 March 2016. View this article in WRRO
- The role of TIGAR in Parkinson's disease. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 42 (pp 34-35)
- Investigating the mechanisms underlying oligodendrocyte dysfunction in C9ORF72 ALS. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 41 (pp 26-27)
- 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)
- A pathological basis for the association of parkinsonism and amyotrophic lateral sclerosis. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 39 (pp 51-51)
- Neurodegeneration caused by intronic expansions of C9ORF72 is a clinically heterogeneous but pathologically distinct disease. LANCET, Vol. 381 (pp 32-32)
- Evidence for an ischemic origin of deep brain 'microbleeds'. CEREBROVASCULAR DISEASES, Vol. 35 (pp 42-42)
- Barrett's Metaplasia: Exploiting a Tissue-engineered Model to Understand the Response of the Oesophageal Squamous Mucosa to Bile and Acid Exposure. JOURNAL OF PATHOLOGY, Vol. 228 (pp S3-S3)
- 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)
- 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)
- Deviations in brain structure as pointers to the role of asymmetry and sex in the genetics of schizophrenia.. AMERICAN JOURNAL OF MEDICAL GENETICS, Vol. 81(6) (pp 533-533)
- A study of sylvian fissure asymmetries in the Runwell 3 series of psychotic brains. SCHIZOPHRENIA RESEARCH, Vol. 18(2-3) (pp XF2-XF2)
Preprints
- Molecular determinants of protein pathogenicity at the single-aggregate level, Cold Spring Harbor Laboratory.
- GRASPS: a simple-to-operate translatome technology reveals omics-hidden disease-associated pathways in TDP-43-related amyotrophic lateral sclerosis, Cold Spring Harbor Laboratory.
- A Y374X TDP43 truncation leads to an altered metabolic profile in amyotrophic lateral sclerosis fibroblasts driven by pyruvate and TCA cycle intermediate alterations. Frontiers in Aging Neuroscience, 15. View this article in WRRO
- Teaching activities
-
I teach neuropathology and neuroanatomy to medical students as well as orthoptics students and postgraduate psychiatry trainees.