Dr Paul Heath
Department of Neuroscience
Senior Scientific Officer
+44 114 222 2254
Full contact details
Department of Neuroscience
385a Glossop Road
- 2007 Senior Scientific Officer, Manager of Affymetrix microarray core facility, University of Sheffield, UK
- 2001–2007 Postdoctoral Research Associate. Academic Neurology Unit, University of Sheffield.
- 1998-2001 Associate programmer, HSBC Bank, Griffin House, Silver Street Head, Sheffield.
- 1994-1998 Postdoctoral Research Associate, Department of Biomedical Science, University of Sheffield.
- 1990-1994 Research Assistant, Department of Biomedical Science, University of Sheffield.
- Jan 1990–Jun 1990 Experimental Officer, Biotechnology, I.C.I. Pharmaceuticals, Alderley Park, Macclesfield, Cheshire.
- 1987-1989 Experimental Officer, I.C.I. Diagnostics, Gadbrook Park, Northwich, Cheshire.
- January to October 1987. Visiting Research Scientist, Department of Microbiology and Molecular Genetics, University of California, Irvine, California,
- 1982-1986 Molecular Biologist / Clinical Cytogeneticist,Centre for Human Genetics, Langhill, 117, Manchester Road, Sheffield.
- 1979-1982 Research Scientist, University Department of Haematology, Royal Hallamshire Hospital, Sheffield.
- Research interests
The role of GluR2 editing in motor neuron disease.
The AMPA receptor subunit GluR2 controls calcium entry to the motor neurone. During development it undergoes post transcriptional RNA editing giving rise to a mature form which blocks the receptor pore. There is evidence which suggests that in some forms of motor neurone disease this process is faulty giving rise to a receptor that becomes calcium permeable. In collaboration with colleagues in Edinburgh I am investigating this evidence in our own material.
Selective vulnerability to neurodegeneration of motor neuron populations.
In motor neuron disease there is a loss of motor neurons from the spinal cord and motor cortex but the motor neurons controlling eye movement (oculomotor) and the pelvic floor are spared. I am currently involved with a project to examine the gene expression profiles of both the spinal cord and oculomotor motor neurons in order to determine what mechanisms might be involved in the differential vulnerability of the two groups.
Microarray analysis of RNA extracted from formalin-fixed paraffin embedded samples.
There is a large archive of tissue samples collected for histological analysis that are formalin fixed and then embedded in paraffin. I have begun a project to develop a reliable methodology to unlock the RNA from these samples and make it available for microarray studies. This will enable us to carry out gene expression studies of some valuable samples in a number of areas.
- Review: Microglia in motor neuron disease. Neuropathology and Applied Neurobiology. View this article in WRRO
- The involvement of regulatory T cells in amyotrophic lateral sclerosis and their therapeutic potential. Amyotrophic lateral sclerosis & frontotemporal degeneration. 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
- NDRG2 expression correlates with neurofibrillary tangles and microglial pathology in the ageing brain. International Journal of Molecular Sciences, 21(1). View this article in WRRO
- C9orf72 expansion within astrocytes reduces metabolic flexibility in amyotrophic lateral sclerosis. Brain, 1-20. View this article in WRRO
- Neutrophil-derived microvesicle induced dysfunction of brain microvascular endothelial cells in vitro. International Journal of Molecular Sciences, 20(20). 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
- Age-associated mRNA and miRNA expression changes in the blood-brain barrier. International Journal of Molecular Sciences, 20(12). View this article in WRRO
- Expression of p16 and p21 in the frontal association cortex of ALS/MND brains suggest neuronal cell cycle dysregulation and astrocyte senescence in early stages of the disease. Neuropathology and Applied Neurobiology. View this article in WRRO
- Mutations in the Glycosyltransferase Domain of GLT8D1 Are Associated with Familial Amyotrophic Lateral Sclerosis. Cell Reports, 26(9), 2298-2306.e5. View this article in WRRO
- The time course of recognition memory impairment and glial pathology in the hAPP-J20 mouse model of Alzheimer’s disease. Journal of Alzheimer's disease : JAD. View this article in WRRO
- Micro-RNAs secreted through astrocyte-derived extracellular vesicles cause neuronal network degeneration in C9orf72 ALS.. EBioMedicine, 40, 626-635. View this article in WRRO
- Endogenous production of IL-1B by breast cancer cells drives metastasis and colonisation of the bone microenvironment.. Clinical Cancer Research, 25(9), 2769-2782. View this article in WRRO
- Metallothionein‐I/II expression associates with the astrocyte DNA damage response and not Alzheimer‐type pathology in the aging brain. Glia, 66(11), 2316-2323. View this article in WRRO
- Loss of IGF1R in human astrocytes alters complex I activity and support for neurons.. Neuroscience, 390, 46-59. View this article in WRRO
- Translating SOD1 Gene Silencing toward the Clinic: A Highly Efficacious, Off-Target-free, and Biomarker-Supported Strategy for fALS. Molecular Therapy : Nucleic Acids, 12, 75-88. View this article in WRRO
- Whole genome sequencing in an acrodermatitis enteropathica family from the Middle East. Dermatology Research and Practice, 2018. View this article in WRRO
- Proteomic and cellular localisation studies suggest non-tight junction cytoplasmic and nuclear roles for occludin in astrocytes. European Journal of Neuroscience, 47(12), 1444-1456. View this article in WRRO
- S5-01-01: AGEING AND NEUROIMMUNOLOGY: WHITE MATTER PATHOLOGY. Alzheimer's & Dementia, 14(7S_Part_31), P1624-P1624.
- P4-059: NEUTROPHIL-DERIVED MICROVESICLE-INDUCED BLOOD BRAIN BARRIER DYSFUNCTION: A POTENTIAL MECHANISM LINKING SYSTEMIC INFLAMMATION AND DEMENTIA. Alzheimer's & Dementia, 14(7S_Part_27), P1455-P1455.
- Protective paraspeckle hyper-assembly downstream of TDP-43 loss of function in amyotrophic lateral sclerosis. Molecular Neurodegeneration, 13(1). View this article in WRRO
- Age‐associated changes in the blood‐brain barrier: comparative studies in human and mouse. Neuropathology and Applied Neurobiology, 44(3), 328-340. View this article in WRRO
- Small RNA Sequencing of Sporadic Amyotrophic Lateral Sclerosis Cerebrospinal Fluid Reveals Differentially Expressed miRNAs Related to Neural and Glial Activity. Frontiers in Neuroscience, 11. View this article in WRRO
- Immuno-Laser-Capture Microdissection for the Isolation of Enriched Glial Populations from Frozen Post-Mortem Human Brain, 273-284.
- Review: Neuropathology and behavioural features of transgenic murine models of Alzheimer's disease. Neuropathology and Applied Neurobiology, 43(7), 553-570. View this article in WRRO
- Targeted Genetic Screen in Amyotrophic Lateral Sclerosis Reveals Novel Genetic Variants with Synergistic Effect on Clinical Phenotype. Frontiers in Molecular Neuroscience, 10, 370-370. View this article in WRRO
- Serum miRNAs miR-206, 143-3p and 374b-5p as potential biomarkers for amyotrophic lateral sclerosis (ALS). Neurobiology of Aging, 55, 123-131. View this article in WRRO
- Review: Astrocytes in Alzheimer's disease and other age-associated dementias: a supporting player with a central role. Neuropathology and Applied Neurobiology, 43(4), 281-298. 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
- C9ORF72 hexanucleotide repeat exerts toxicity in a stable, inducible motor neuronal cell model, which is rescued by partial depletion of Pten. Human Molecular Genetics, 26(6), 1133-1145. View this article in WRRO
- Spinal muscular atrophy: Factors that modulate motor neurone vulnerability.. Neurobiology of Disease. View this article in WRRO
- Oligodendrocytes contribute to motor neuron death in ALS via SOD1-dependent mechanism. Proceedings of the National Academy of Sciences of the United States of America, 113(42), E6496-E6505. View this article in WRRO
- Gene expression profiling of the astrocyte transcriptome in multiple sclerosis normal appearing white matter reveals a neuroprotective role. Journal of Neuroimmunology, 299, 139-146. View this article in WRRO
- Immune response in peripheral axons delays disease progression in SOD1(G93A) mice.. Journal of Neuroinflammation, 13(1), 261-261. View this article in WRRO
- Expression microdissection isolation of enriched cell populations from archival brain tissue. Journal of Neuroscience Methods, 268, 125-130. View this article in WRRO
- The genetics of amyotrophic lateral sclerosis: current insights. Degenerative Neurological and Neuromuscular Disease, 6, 49-64. View this article in WRRO
- Neuronal DNA damage response-associated dysregulation of signalling pathways and cholesterol metabolism at the earliest stages of Alzheimer-type pathology. Neuropathology and Applied Neurobiology, 42(2), 167-179. View this article in WRRO
- Insulin and IGF1 signalling pathways in human astrocytes in vitro and in vivo; characterisation, subcellular localisation and modulation of the receptors. Molecular Brain, 8(1). View this article in WRRO
- 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. Neuroscience Letters, 609, 11-17. View this article in WRRO
- Lysosomal and phagocytic activity is increased in astrocytes during disease progression in the SOD1 G93A mouse model of amyotrophic lateral sclerosis. FRONTIERS IN CELLULAR NEUROSCIENCE, 9. View this article in WRRO
- Lysosomal and phagocytic activity is increased in astrocytes during disease progression in the SOD1 G93A mouse model of amyotrophic lateral sclerosis. Frontiers in Cellular Neuroscience, 9, 410-410. View this article in WRRO
- Binding loci of RelA-containing nuclear factor-kappaB dimers in promoter regions of PHM1-31 myometrial smooth muscle cells. Molecular Human Reproduction, 21(11), 865-883. View this article in WRRO
- Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain. Brain Pathology, 25(5), 565-574. View this article in WRRO
- A neuronal DNA damage response is detected at the earliest stages of Alzheimer's neuropathology and correlates with cognitive impairment in the Medical Research Council's Cognitive Function and Ageing Study ageing brain cohort. Neuropathology and Applied Neurobiology, 41(4), 483-496. View this article in WRRO
- 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
- 227 Luzp4 defines a new mRNA export pathway in cancer cells. European Urology Supplements, 14(2), e227-e227b.
- Luzp4 defines a new mRNA export pathway in cancer cells. Nucleic Acids Research, 43(4), 2353-2366. 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
- 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.
- Pulsatile exposure to simulated reflux leads to changes in gene expression in a 3D model of oesophageal mucosa.. Int J Exp Pathol, 95(3), 216-228. View this article in WRRO
- Alpha-synuclein mRNA expression in oligodendrocytes in MSA. GLIA. View this article in WRRO
- 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 Medical Research Council Cognitive Function and Ageing Study (MRC-CFAS) cohort.. Neuropathol Appl Neurobiol, 40(7), 802-814.
- The battle of the sexes starts in the oviduct: modulation of oviductal transcriptome by X and Y-bearing spermatozoa. BMC Genomics, 15. View this article in WRRO
- Comparison of blood RNA extraction methods used for gene expression profiling in amyotrophic lateral sclerosis.. PLoS One, 9(1), e87508. View this article in WRRO
- Transcriptomic indices of fast and slow disease progression in two mouse models of amyotrophic lateral sclerosis.. Brain, 136(Pt 11), 3305-3332.
- TigarB causes mitochondrial dysfunction and neuronal loss in PINK1 deficiency.. Ann Neurol, 74(6), 837-847. View this article in WRRO
- The Effect of SOD1 Mutation on Cellular Bioenergetic Profile and Viability in Response to Oxidative Stress and Influence of Mutation-Type.. Plos One, 6(8), e68256-e68256. View this article in WRRO
- S[+] Apomorphine is a CNS penetrating activator of the Nrf2-ARE pathway with activity in mouse and patient fibroblast models of amyotrophic lateral sclerosis.. Free Radic Biol Med, 61, 438-452.
- Calcium dysregulation in relation to Alzheimer-type pathology in the ageing brain.. Neuropathol Appl Neurobiol, 39(7), 788-799.
- Investigating cell death mechanisms in amyotrophic lateral sclerosis using transcriptomics.. Front Cell Neurosci, 7, 259. View this article in WRRO
- Neuronal dark matter: the emerging role of microRNAs in neurodegeneration.. Front Cell Neurosci, 7, 178. View this article in WRRO
- Unravelling the enigma of selective vulnerability in neurodegeneration: motor neurons resistant to degeneration in ALS show distinct gene expression characteristics and decreased susceptibility to excitotoxicity.. Acta Neuropathol, 125(1), 95-109. View this article in WRRO
- Gene expression profiling in human neurodegenerative disease.. Nat Rev Neurol, 8(9), 518-530.
- Isolation of enriched glial populations from post-mortem human CNS material by immuno-laser capture microdissection.. J Neurosci Methods, 208(2), 108-113.
- Early developing pig embryos mediate their own environment in the maternal tract.. PLoS One, 7(3), e33625. View this article in WRRO
- Microarray analysis of the astrocyte transcriptome in the aging brain: relationship to Alzheimer's pathology and APOE genotype. NEUROBIOL AGING, 32(10), 1795-1807.
- Dysregulation of astrocyte-motoneuron cross-talk in mutant superoxide dismutase 1-related amyotrophic lateral sclerosis.. Brain, 134(Pt 9), 2627-2641.
- P3-156: Microarray analysis of the astrocyte transcriptome in the aging brain: Relationship to Alzheimer's pathology and APOE genotype. Alzheimer's & Dementia, 7, S566-S566.
- Phosphatase and tensin homologue/protein kinase B pathway linked to motor neuron survival in human superoxide dismutase 1-related amyotrophic lateral sclerosis.. Brain, 134(Pt 2), 506-517. View this article in WRRO
- Regulation of neutrophil senescence by microRNAs.. PLoS One, 6(1), e15810. View this article in WRRO
- Riboflavin depletion impairs cell proliferation in adult human duodenum: Identification of potential effectors. Digestive Diseases and Sciences, 56(4), 1007-1019.
- Downregulation of genes with a function in axon outgrowth and synapse formation in motor neurones of the VEGFdelta/delta mouse model of amyotrophic lateral sclerosis.. BMC Genomics, 11, 203. View this article in WRRO
- Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS).. PLoS One, 5(3), e9872. View this article in WRRO
- Microarray profiling reveals CXCR4a is downregulated by blood flow in vivo and mediates collateral formation in zebrafish embryos.. Physiol Genomics, 38(3), 319-327.
- Transcriptional response of the neuromuscular system to exercise training and potential implications for ALS.. J Neurochem, 109(6), 1714-1724.
- Microarray RNA expression analysis of cerebral white matter lesions reveals changes in multiple functional pathways.. Stroke, 40(2), 369-375.
- Sphingosine-1-phosphate mediates transcriptional regulation of key targets associated with survival, proliferation, and pluripotency in human embryonic stem cells.. Stem Cells Dev, 17(6), 1195-1205.
- Microarray analysis of the cellular pathways involved in the adaptation to and progression of motor neuron injury in the SOD1 G93A mouse model of familial ALS.. J Neurosci, 27(34), 9201-9219.
- Adaptation to culture of human embryonic stem cells and oncogenesis in vivo.. Nat Biotechnol, 25(2), 207-215.
- Gene expression assays.. Adv Clin Chem, 44, 247-292.
- Impairment of mitochondrial anti-oxidant defence in SOD1-related motor neuron injury and amelioration by ebselen. Brain, 129(7), 1693-1709.
- Detection of mutations in whole genome-amplified DNA from laser-microdissected neurons.. J Neurosci Methods, 147(1), 65-67.
- Mutant SOD1 alters the motor neuronal transcriptome: implications for familial ALS.. Brain, 128(Pt 7), 1686-1706.
- Analysis of the cytosolic proteome in a cell culture model of familial amyotrophic lateral sclerosis reveals alterations to the proteasome, antioxidant defenses, and nitric oxide synthetic pathways.. J Biol Chem, 278(8), 6371-6383.
- Quantitative assessment of AMPA receptor mRNA in human spinal motor neurons isolated by laser capture microdissection.. Neuroreport, 13(14), 1753-1757.
- Update on the glutamatergic neurotransmitter system and the role of excitotoxicity in amyotrophic lateral sclerosis.. Muscle Nerve, 26(4), 438-458.
- Selective loss of neurofilament expression in Cu/Zn superoxide dismutase (SOD1) linked amyotrophic lateral sclerosis.. J Neurochem, 82(5), 1118-1128.
- Mitochondrial DNA mutations in Alzheimer's disease. BIOCHEM BIOPH RES CO, 241(2), 221-225.
- MAL mRNA is induced during the differentiation of human embryonal carcinoma cells into neurons and is also localised within specific regions of the human brain.. Differentiation, 62(2), 97-105.
- Selective loss of cholinergic receptors following unilateral intracortical injection of volkensin. EXP NEUROL, 147(1), 183-191.
- Neuronal degeneration by suicide transport following injection of volkensin into rat cerebral cortex.. Exp Neurol, 147(1), 192-203.
- Individuals with schizophrenia have an increased incidence of the H2R649G allele for the histamine H2 receptor gene.. Mol Psychiatry, 1(6), 466-469.
- Allelic variations of the human histamine H2 receptor gene.. Neuroreport, 7(7), 1293-1296.
- The relative importance of premortem acidosis and postmortem interval for human brain gene expression studies: Selective mRNA vulnerability and comparison with their encoded proteins. NEUROSCI LETT, 200(3), 151-154.
- Differential changes in glutamate receptor subunit messenger RNAs in rat brain after haloperidol treatment. Journal of Psychopharmacology, 8(4), 196-203.
- EFFECT OF ENTORHINAL INJECTION OF VOLKENSIN ON THE STRUCTURE AND NEUROTRANSMITTER RECEPTORS OF THE HIPPOCAMPUS. BRIT J PHARMACOL, 108, P51-P51.
- CLINICAL MANIFESTATIONS OF TRISOMY-5Q. J MED GENET, 24(3), 180-184.
- THE USE OF A CELL-FREE SYNTHESIS SYSTEM FOR THE STUDY OF FACTOR-FVIII. THROMB HAEMOSTASIS, 46(1), 166-166.
- Advanced Glycation End Product Formation in Human Cerebral Cortex Increases With Alzheimer-Type Neuropathologic Changes but Is Not Independently Associated With Dementia in a Population-Derived Aging Brain Cohort. Journal of Neuropathology & Experimental Neurology.
- Human axial progenitors generate trunk neural crest cells. View this article in WRRO
- Transcriptome Analysis of Gene Expression Provides New Insights into the Effect of Mild Therapeutic Hypothermia on Primary Human Cortical Astrocytes Cultured under Hypoxia. Frontiers in Cellular Neuroscience, 11. View this article in WRRO
- Paternal effects in a wild‐type zebrafish implicate a role of sperm‐derived small RNAs. Molecular Ecology. View this article in WRRO
- An aspect of Alzheimer neuropathology after suicide transport damage, Cell and Animal Models in Aging and Dementia Research (pp. 231-243). Springer Vienna
Conference proceedings papers
- DNA Methylation in Amyotrophic Lateral Sclerosis. JOURNAL OF PATHOLOGY, Vol. 249 (pp S15-S15)
- Investigating senescence activation in response to oxidative DNA damage in neurones in vitro. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 45 (pp 39-39)
- Early cellular changes and cognitive decline in an Alzheimer's mouse model. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 43 (pp 42-43)
- Neuronal senescence as a contributor to neurodegeneration. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 43 (pp 43-43)
- The role of microRNAs in mediating a state of enhanced endometrial receptivity in response to trophoblast cells: an integrative analysis. HUMAN REPRODUCTION, Vol. 30 (pp 106-106)
- Investigating RNA editing in the pathogenesis of amyotrophic lateral sclerosis. FEBS JOURNAL, Vol. 281 (pp 685-686)
- Oxidative stress and DNA damage in cerebral white matter lesions of the ageing human brain. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 40 (pp 33-34)
- 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)
- Oxidative stress and DNA damage in cerebral white matter lesions of the ageing human brain. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 39 (pp 36-37)
- Microarray analysis of the astrocyte transcriptome in normal appearing white matter in multiple sclerosis. JOURNAL OF NEUROIMMUNOLOGY, Vol. 253(1-2) (pp 54-54)
- 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)
- DYSREGULATION OF THE CROSS-TALK WITH ASTROCYTES AS A CONTRIBUTORY FACTOR TO MOTOR NEURON INJURY IN MOTOR NEURON DISEASE. JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol. 83(3)
- 156 Motor neurones subtypes resistant to degeneration in amyotrophic lateral sclerosis show distinct synaptic characteristics across species. Journal of Neurology, Neurosurgery & Psychiatry, Vol. 83(3) (pp e1.110-e1)
- 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)
- TARDBP mutations, amyotrophic lateral sclerosis and alternative splicing. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 37 (pp 20-20)
- 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)
- TRANSCRIPTIONAL PROFILING OF SPINAL MOTOR NEURONES IN THE VEGF(delta/delta) MOUSE MODEL OF AMYOTROPHIC LATERAL SCLEROSIS. JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol. 80(11)
- Identifying Regulatory Gene Networks in the Myometrium Governed by NF-kappa B. REPRODUCTIVE SCIENCES, Vol. 16(3) (pp 113A-113A)
- Determining the transcriptional effect of shear stress in vivo. HEART, Vol. 93(2)
- The role of microglial cells in MND. NEURON GLIA BIOLOGY, Vol. 2 (pp S56-S56)
- Sheffield Hospitals Charitable Trust