Prof Stephen Davies

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Name: Stephen Davies Email: s.w.davies@ucl.ac.uk
Title: Prof Tel: 020 7679 2677
Department: Cell & Developmental Biology Fax: 020 7679 2677
Position: Principal Teaching Fellow Address: Department of Cell & Developmental Biology, UCL, Gower Street, London, WC1E 6BT
Research Domain: Basic Life Sciences, Neuroscience Web Page: Personal Web Page

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Research Description

The neuronal cell nucleus has a characteristic and highly specialised organisation. The nucleolus appears to act as a central organising region around which there is a complex organisation of subnuclear structures, such as the perinucleolar â??rosetteâ?? and a large perinucleolar â??capâ?? of heterochromatin. We are currently defining the molecular and ultrastructural composition of these domains. The rosette is made up of 1-2 domains containing the Cajal Body protein p80 coilin together with Nopp140 and the SMN complex , the remainder contain Nopp140. The heterochromatin caps contain large areas of MeCP2 and are associated with smaller domains containing the chromosome centromeres or the polycomb protein complex. All these areas are variably marked by trimethylated histones. We are further defining this complex organisation by comparing it with 1) the spatial patterns of gene expression occurring in neurons in vivo and 2) the 3d spatial arrangement of genes within the nucleus of defined neurons Why do we think that this complex arrangement of neuronal nuclear structure is of importance for human neurological disease? We have shown that in Huntingtonâ??s disease the neuronal nucleus reorganises to accommodate a large intranuclear inclusion such that the perinucleolar rosette is disrupted to allow movement of the Cajal body like p80 coilin positve structure to attach to the newly formed inclusion. This results in a profound rearrangement of the nucleolar structure, dissociation away from defined chromosomal domains and transcriptional dysregulation. Similar disruption of these structures occurs in spinal muscular atrophy (SMA), fragile X tremor ataxia syndrome (FXTAS), frontotemporal dementia (FTD) and autism spectrum disorder (ASD). We are currently investigating the functional consequences of nuclear disruption in these conditions.

Research Activities

The ultrastructural and molecular organisation of the neuronal nucleus

Education Description

UCL Collaborators

External Collaborators

Publications

    2007

    • Raza AS, Davies SW (2007). Progressive neuronal atrophy in a mouse model of Huntington's disease. J ANAT, 210(5), 607 - 607.

    2000

    • Turmaine M, Raza A, Mahal A, Mangiarini L, Bates GP, Davies SW (2000). Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease. Proceedings of the National Academy of Sciences of the United States of America, 97, 8093 - 8097.
    • O'Sullivan JD, Hanagasi HA, Daniel SE, Tidswell P, Davies SW, Lees AJ (2000). Neuronal intranuclear inclusion disease and juvenile parkinsonism. Movement Disorders, 15(5), 990 - 995.

    1999

    • Sathasivam K, Hobbs C, Mangiarini L, Mahal A, Turmaine M, Doherty P, Davies SW, Bates GP (1999). Transgenic models of Huntington's disease. PHILOS T R SOC B, 354(1386), 963 - 969.
    • Davies SW, Turmaine M, Cozens BA, Raza AS, Mangiarini L, Bates GP (1999). From neuronal inclusions to neurodegeneration: Neuropathological investigation of a transgenic mouse model of Huntington's Disease. Philosophical Transactions of the Royal Society B: Biological Sciences, 354, 971 - 979.
    • Davies SW, Turmaine M, Cozens BA, Raza AS, Mahal A, Mangiarini L, Bates GP (1999). From neuronal inclusions to neurodegeneration: neuropathological investigation of a transgenic mouse model of Huntington's disease.. Philos Trans R Soc Lond B Biol Sci, 354(1386), 981 - 989.
    • Sathasivam K, Hobbs C, Mangiarini L, Mahal A, Turmaine M, Doherty P, Davies SW, Bates GP (1999). Transgenic models of Huntington's disease. Philosophical Transactions of the Royal Society B: Biological Sciences, 354, 957 - 961.
    • Davies SW, Sathasivam K, Hobbs C, Doherty P, Mangiarini L, Scherzinger E, Wanker EE, Bates GP (1999). Detection of polyglutamine aggregation in mouse models. In Wetzel R (Ed.), Methods in Enzymology 309: Amyloid, Prions, and Protein Aggregates (pp. 687 - 701). : Academic Press.
    • Reynolds GP, Dalton CF, Tillery CL, Mangiarini L, Davies SW, Bates GP (1999). Brain neurotransmitter deficits in mice transgenic for the Huntington's disease mutation. Journal of Neurochemistry, 72, 1774 - 1776.
    • Sathasivam K, Hobbs C, Turmaine M, Mangiarini L, Mahal A, Bertaux F, Wanker EE, Doherty P, Davies SW, Bates GP (1999). Formation of polyglutamine inclusions in non-CNS tissue. Human Molecular Genetics, 8, 813 - 822.
    • Reynolds GP, Dalton CF, Tillery CL, Mangiarini L, Davies SW, Bates GP (1999). Brain neurotransmitter deficits in mice transgenic for the Huntington's disease mutation. J NEUROCHEM, 72(4), 1773 - 1776.
    • Cha J-HJ, Frey AS, Alsdorf SA, Kerner JA, Kosinski CM, Mangiarini L, Penney JB, Davies SW, Bates GP, Young AB (1999). Altered neurotransmitter receptor expression in transgenic mouse models of Huntington's Disease. Philosophical Transactions of the Royal Society B: Biological Sciences, 354, 981 - 989.

    1998

    • Bates GP, Wanker EE, Davies SW (1998). Murine models of Huntington's Disease. In Wells RD, Warren ST (Ed.), Genetic Instabilities and Hereditary Neurological Diseases (pp. 355 - 370). : Academic Press.
    • Davies SW, Beardsall K, Turmaine M, DiFiglia M, Aronin N, Bates GP (1998). Are neuronal intranuclear inclusions the common neuropathology of triplet-repeat disorders with polyglutamine-repeat expansions?. The Lancet, 351, 131 - 133.
    • Bates GP, Mangiarini L, Wanker EE, Davies SW (1998). Polyglutamine expansion and Huntington's Disease. Biochemical Society Transactions, 26(3), 471 - 475.
    • Goedert M, Spillantini MG, Davies SW (1998). Filamentous nerve cell inclusions in neurodegenerative diseases. CURR OPIN NEUROBIOL, 8(5), 619 - 632.
    • Becher MW, Kotzuk JA, Sharp AH, Davies SW, Bates GP, Price DL, Ross CA (1998). Intranuclear neuronal inclusions in Huntington's disease and dentatorubral and pallidoluysian atrophy: Correlation between the density of inclusions and IT15 CAG triplet repeat length. NEUROBIOL DIS, 4(6), 387 - 397.
    • Becher MW, Kotzuk JA, Sharp AH, Davies SW, Bates GP, Price DL, Ross CA (1998). Intranuclear Neuronal Inclusions: A novel marker in Huntington's disease which correlates with CAG triplet repeat length. Neurobiology of Disease, 4, 387 - 395.
    • Cha JJ, Kosinski CM, Kerner JA, Alsdorf SA, Mangiarini L, Davies SW, Penney JB, Bates GP, Young AB (1998). Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human Huntington disease gene. Proceedings of the National Academy of Sciences of the United States of America, 95, 6480 - 6485.
    • Goedert M, Spillantini M, Davies SW (1998). Filamentous intracellular inclusions and neurodegenerative disease. Current Opinion in Neurobiology, 8, 619 - 632.
    • Bates GP, Mangiarini L, Davies SW (1998). Transgenic mice in the study of polyglutamine repeat expansion diseases. Brain Pathology, 8, 699 - 714.

    1997

    • Mangiarini L, Davies SW, Bates GP (1997). Animal models of human disease: A mouse model of Huntington's disease. Comparative Pathology Bulletin, 30, 3 - 6.
    • Scherzinger E, Lurz R, Turmaine M, Mangiarini L, Hollenbach B, Hasenbank R, Bates GP, Davies SW, Lehrach H, Wanker EE (1997). Huntingtin encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell, 90, 549 - 558.
    • Bates GP, Mangiarini L, Mahal A, Davies SW (1997). Transgenic models of HD. Human Molecular Genetics, 6, 1633 - 1637.
    • Bates GP, Davies SW (1997). Transgenic mouse models of neurodegenerative disease caused by CAG/polyglutamine expansions. Molecular Medicine Today, 3, 508 - 515.
    • Davies SW, Turmaine M, Cozens BA, DiFiglia M, Sharp AH, Ross CA, Scherzinger E, Wanker EE, Mangiarini L, Bates GP (1997). Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell, 90, 537 - 548.
    • Hollen KM, Nakabeppu Y, Davies SW (1997). Changes in the expression of deltaFosB and the Fos family proteins following NMDA receptor activation in the rat striatum. Molecular Brain Research, 47, 31 - 43.
    • Davies SW, Turmaine M, Cozens BA, Mangiarini L, Bates GP (1997). Formation of neuronal intranuclear inclusions (NII) underlies the neurological dysfunction in mice transgenic for the HD mutation. BRAIN PATHOL, 7(3), 1018 - 1018.
    • DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N (1997). Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science, 277, 1990 - 1993.

    1993

    • Purkiss RJ, Legg MD, Hunt SP, Davies SW (1993). Immediate early gene expression in the rat forebrain following striatal infusion of quinolinic acid.. Eur J Neurosci, 5(12), 1653 - 1662.

    1992

    • Davies SW, Beardsall K (1992). Nerve growth factor selectively prevents excitotoxin induced degeneration of striatal cholinergic neurones.. Neurosci Lett, 140(2), 161 - 164.

    1990

    • Parnavelas JG, Jeffery G, Cope J, Davies SW (1990). Early lesion of mystacial vibrissae in rats results in an increase of somatostatin-labelled cells in the somatosensory cortex.. Exp Brain Res, 82(3), 658 - 662.

    1988

    • Davies SW, Roberts PJ (1988). Sparing of cholinergic neurons following quinolinic acid lesions of the rat striatum.. Neuroscience, 26(2), 387 - 393.
    • Davies SW, Roberts PJ (1988). Model of Huntington's disease.. Science, 241(4864), 474 - 475.