Professor Maria Grazia Spillantini FRS FMedSci University positionProfessor Professor Maria Grazia Spillantini FRS FMedSci is pleased to consider applications from prospective PhD students. DepartmentsDepartment of Clinical Neurosciences InstitutesClifford Albutt Building Home pagehttps://spillantinilab.medschl.cam.ac.uk Research ThemeInterestsOur interest is in the identification of the mechanisms leading to neuronal death and clinical phenotype in diseases such as Alzheimer's disease, Parkinson's disease and frontotemporal dementia. In particular we study the role of microtubule-associated protein tau and alpha-synuclein aggregation in the pathogenesis of tauopathies and alpha-synucleinopathies. Our work extends from genetic studies in patients to disease models. The aim is to identify mechanism-based therapies for these disorders.  Lewy Bodies in Parkinson's disease substantia nigra stained for alpha-synuclein Click image to view full-size Research Focus
EquipmentFluorescence microscopy Immunohistochemistry Molecular Biology Protein purification Western blotting Collaborators
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Key publicationsGarcia-Reitböck P, Anichtchik O, Bellucci A, Iovino M, Ballini C, Fineberg E, Ghetti B, Della Corte L, Spano P, Tofaris GK, Goedert M, Spillantini MG (2010), “SNARE protein redistribution and synaptic failure in a transgenic mouse model of Parkinson's disease.” Brain 133(Pt 7):2032-44 Details Iovino M, Patani R, Watts C, Chandran S, Spillantini MG (2010), “Human stem cell-derived neurons: a system to study human tau function and dysfunction.” PLoS One 5(11):e13947 Details Magnani E, Fan J, Gasparini L, Golding M, Williams M, Schiavo G, Goedert M, Amos LA, Spillantini MG (2007), “Interaction of tau protein with the dynactin complex.” EMBO J 26(21):4546-54 Details Bellucci A, Westwood AJ, Ingram E, Casamenti F, Goedert M, Spillantini MG (2004), “Neuroinflammation in mice transgenic for human P301S tau protein” American Journal of Pathology 165(5):1643-52 Details Spillantini MG, Crowther RA, Jakes R, Cairns NJ, Lantos PL, Goedert M (1998), “Filamentous alpha-synuclein inclusions link multiple system atrophy with Parkinson's disease and dementia with Lewy bodies.” Neurosci Lett 251(3):205-8 Details Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M (1998), “alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies.” Proc Natl Acad Sci U S A 95(11):6469-73 Details Spillantini MG, Murrell JR, Goedert M, Farlow MR, Klug A, Ghetti B (1998), “Mutation in the tau gene in familial multiple system tauopathy with presenile dementia.” Proc Natl Acad Sci U S A 95(13):7737-41 Details Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997), “Alpha-synuclein in Lewy bodies.” Nature 388(6645):839-40 Details Publications2014Ferrari R, Hernandez DG, Nalls MA, Rohrer JD, Ramasamy A, Kwok JB, Dobson-Stone C, Brooks WS, Schofield PR, Halliday GM, Hodges JR, Piguet O, Bartley L, Thompson E, Haan E, Hernández I, Ruiz A, Boada M, Borroni B, Padovani A, Cruchaga C, Cairns NJ, Benussi L, Binetti G, Ghidoni R, Forloni G, Galimberti D, Fenoglio C, Serpente M, Scarpini E, Clarimón J, Lleó A, Blesa R, Waldö ML, Nilsson K, Nilsson C, Mackenzie IR, Hsiung GY, Mann DM, Grafman J, Morris CM, Attems J, Griffiths TD, McKeith IG, Thomas AJ, Pietrini P, Huey ED, Wassermann EM, Baborie A, Jaros E, Tierney MC, Pastor P, Razquin C, Ortega-Cubero S, Alonso E, Perneczky R, Diehl-Schmid J, Alexopoulos P, Kurz A, Rainero I, Rubino E, Pinessi L, Rogaeva E, St George-Hyslop P, Rossi G, Tagliavini F, Giaccone G, Rowe JB, Schlachetzki JC, Uphill J, Collinge J, Mead S, Danek A, Van Deerlin VM, Grossman M, Trojanowski JQ, van der Zee J, Deschamps W, Van Langenhove T, Cruts M, Van Broeckhoven C, Cappa SF, Le Ber I, Hannequin D, Golfier V, Vercelletto M, Brice A, (2014), “Frontotemporal dementia and its subtypes: a genome-wide association study.” Lancet Neurol 13(7):686-99 Details Herva ME, Zibaee S, Fraser G, Barker RA, Goedert M, Spillantini MG (2014), “Anti-amyloid compounds inhibit alpha-synuclein aggregation induced by Protein Misfolding Cyclic Amplification (PMCA).” J Biol Chem Details Iovino M, Pfisterer U, Holton JL, Lashley T, Swingler RJ, Calo L, Treacy R, Revesz T, Parmar M, Goedert M, Muqit MM, Spillantini MG (2014), “The novel MAPT mutation K298E: mechanisms of mutant tau toxicity, brain pathology and tau expression in induced fibroblast-derived neurons.” Acta Neuropathol 127(2):283-95 Details 2013Anichtchik O, Calo L, Spillantini MG (2013), “Synaptic dysfunction in synucleinopathies.” CNS Neurol Disord Drug Targets 12(8):1094-100 Details Bezard E, Yue Z, Kirik D, Spillantini MG (2013), “Animal models of Parkinson's disease: limits and relevance to neuroprotection studies.” Mov Disord 28(1):61-70 Details Dassie E, Andrews MR, Bensadoun JC, Cacquevel M, Schneider BL, Aebischer P, Wouters FS, Richardson JC, Hussain I, Howlett DR, Spillantini MG, Fawcett JW (2013), “Focal expression of adeno-associated viral-mutant tau induces widespread impairment in an APP mouse model.” Neurobiol Aging 34(5):1355-68 Details Garcia-Reitboeck P, Anichtchik O, Dalley JW, Ninkina N, Tofaris GK, Buchman VL, Spillantini MG (2013), “Endogenous alpha-synuclein influences the number of dopaminergic neurons in mouse substantia nigra.” Exp Neurol 248:541-5 Details Goedert M, Spillantini MG, Del Tredici K, Braak H (2013), “100 years of Lewy pathology.” Nat Rev Neurol 9(1):13-24 Details King A, Al-Sarraj S, Troakes C, Smith BN, Maekawa S, Iovino M, Spillantini MG, Shaw CE (2013), “Mixed tau, TDP-43 and p62 pathology in FTLD associated with a C9ORF72 repeat expansion and p.Ala239Thr MAPT (tau) variant.” Acta Neuropathol 125(2):303-10 Details Mellone M, Kestoras D, Andrews MR, Dassie E, Crowther RA, Stokin GB, Tinsley J, Horne G, Goedert M, Tolkovsky AM, Spillantini MG (2013), “Tau pathology is present in vivo and develops in vitro in sensory neurons from human P301S tau transgenic mice: a system for screening drugs against tauopathies.” J Neurosci 33(46):18175-89 Details Romberg C, Yang S, Melani R, Andrews MR, Horner AE, Spillantini MG, Bussey TJ, Fawcett JW, Pizzorusso T, Saksida LM (2013), “Depletion of perineuronal nets enhances recognition memory and long-term depression in the perirhinal cortex.” J Neurosci 33(16):7057-65 Details Spillantini MG, Goedert M (2013), “Tau pathology and neurodegeneration.” Lancet Neurol 12(6):609-22 Details 2012Baiguera C, Alghisi M, Pinna A, Bellucci A, De Luca MA, Frau L, Morelli M, Ingrassia R, Benarese M, Porrini V, Pellitteri M, Bertini G, Fabene PF, Sigala S, Spillantini MG, Liou HC, Spano PF, Pizzi M (2012), “Late-onset Parkinsonism in NF?B/c-Rel-deficient mice.” Brain 135(Pt 9):2750-65 Details Costa C, Sgobio C, Siliquini S, Tozzi A, Tantucci M, Ghiglieri V, Di Filippo M, Pendolino V, de Iure A, Marti M, Morari M, Spillantini MG, Latagliata EC, Pascucci T, Puglisi-Allegra S, Gardoni F, Di Luca M, Picconi B, Calabresi P (2012), “Mechanisms underlying the impairment of hippocampal long-term potentiation and memory in experimental Parkinson's disease.” Brain 135(Pt 6):1884-99 Details Goedert M, Ghetti B, Spillantini MG (2012), “Frontotemporal dementia: implications for understanding Alzheimer disease.” Cold Spring Harb Perspect Med 2(2):a006254 Details Winder-Rhodes SE, Garcia-Reitböck P, Ban M, Evans JR, Jacques TS, Kemppinen A, Foltynie T, Williams-Gray CH, Chinnery PF, Hudson G, Burn DJ, Allcock LM, Sawcer SJ, Barker RA, Spillantini MG (2012), “Genetic and pathological links between Parkinson's disease and the lysosomal disorder Sanfilippo syndrome.” Mov Disord 27(2):312-5 Details 2011Anfossi M, Vuono R, Maletta R, Virdee K, Mirabelli M, Colao R, Puccio G, Bernardi L, Frangipane F, Gallo M, Geracitano S, Tomaino C, Curcio SA, Zannino G, Lamenza F, Duyckaerts C, Spillantini MG, Losso MA, Bruni AC (2011), “Compound heterozygosity of 2 novel MAPT mutations in frontotemporal dementia.” Neurobiol Aging 32(4):757.e1-757.e11 Details Bellucci A, Bugiani O, Ghetti B, Spillantini MG (2011), “Presence of reactive microglia and neuroinflammatory mediators in a case of frontotemporal dementia with P301S mutation.” Neurodegener Dis 8(4):221-9 Details Bellucci A, Navarria L, Falarti E, Zaltieri M, Bono F, Collo G, Spillantini MG, Missale C, Spano P (2011), “Redistribution of DAT/?-synuclein complexes visualized by "in situ" proximity ligation assay in transgenic mice modelling early Parkinson's disease.” PLoS One 6(12):e27959 Details Goedert M, Spillantini MG (2011), “Pathogenesis of the tauopathies.” J Mol Neurosci 45(3):425-31 Details Love S, Spillantini MG (2011), “Unpicking frontotemporal lobar degeneration.” Brain 134(Pt 9):2453-5 Details Shelkovnikova TA, Ustyugov AA, Millership S, Peters O, Anichtchik O, Spillantini MG, Buchman VL, Bachurin SO, Ninkina NN (2011), “Dimebon does not ameliorate pathological changes caused by expression of truncated (1-120) human alpha-synuclein in dopaminergic neurons of transgenic mice.” Neurodegener Dis 8(6):430-7 Details Spillantini MG, Iovino M, Vuono R (2011), “Release of growth factors by neuronal precursor cells as a treatment for diseases with tau pathology.” Arch Ital Biol 149(2):215-23 Details 2010Anderson JM, Patani R, Reynolds R, Nicholas R, Compston A, Spillantini MG, Chandran S (2010), “Abnormal tau phosphorylation in primary progressive multiple sclerosis.” Acta Neuropathol 119(5):591-600 Details Bruni AC, Bernardi L, Colao R, Rubino E, Smirne N, Frangipane F, Terni B, Curcio SA, Mirabelli M, Clodomiro A, Di Lorenzo R, Maletta R, Anfossi M, Gallo M, Geracitano S, Tomaino C, Muraca MG, Leotta A, Lio SG, Pinessi L, Rainero I, Sorbi S, Nee L, Milan G, Pappatà S, Postiglione A, Abbamondi N, Forloni G, St George Hyslop P, Rogaeva E, Bugiani O, Giaccone G, Foncin JF, Spillantini MG, Puccio G (2010), “Worldwide distribution of PSEN1 Met146Leu mutation: a large variability for a founder mutation.” Neurology 74(10):798-806 Details Hampton DW, Webber DJ, Bilican B, Goedert M, Spillantini MG, Chandran S (2010), “Cell-mediated neuroprotection in a mouse model of human tauopathy.” J Neurosci 30(30):9973-83 Details Hodges JR, Mitchell J, Dawson K, Spillantini MG, Xuereb JH, McMonagle P, Nestor PJ, Patterson K (2010), “Semantic dementia: demography, familial factors and survival in a consecutive series of 100 cases.” Brain 133(Pt 1):300-6 Details Pan-Montojo F, Anichtchik O, Dening Y, Knels L, Pursche S, Jung R, Jackson S, Gille G, Spillantini MG, Reichmann H, Funk RH (2010), “Progression of Parkinson's disease pathology is reproduced by intragastric administration of rotenone in mice.” PLoS One 5(1):e8762 Details Rosi MC, Luccarini I, Grossi C, Fiorentini A, Spillantini MG, Prisco A, Scali C, Gianfriddo M, Caricasole A, Terstappen GC, Casamenti F (2010), “Increased Dickkopf-1 expression in transgenic mouse models of neurodegenerative disease.” J Neurochem 112(6):1539-51 Details Scattoni ML, Gasparini L, Alleva E, Goedert M, Calamandrei G, Spillantini MG (2010), “Early behavioural markers of disease in P301S tau transgenic mice.” Behav Brain Res 208(1):250-7 Details Van Deerlin VM, Sleiman PM, Martinez-Lage M, Chen-Plotkin A, Wang LS, Graff-Radford NR, Dickson DW, Rademakers R, Boeve BF, Grossman M, Arnold SE, Mann DM, Pickering-Brown SM, Seelaar H, Heutink P, van Swieten JC, Murrell JR, Ghetti B, Spina S, Grafman J, Hodges J, Spillantini MG, Gilman S, Lieberman AP, Kaye JA, Woltjer RL, Bigio EH, Mesulam M, Al-Sarraj S, Troakes C, Rosenberg RN, White CL 3rd, Ferrer I, Lladó A, Neumann M, Kretzschmar HA, Hulette CM, Welsh-Bohmer KA, Miller BL, Alzualde A, de Munain AL, McKee AC, Gearing M, Levey AI, Lah JJ, Hardy J, Rohrer JD, Lashley T, Mackenzie IR, Feldman HH, Hamilton RL, Dekosky ST, van der Zee J, Kumar-Singh S, Van Broeckhoven C, Mayeux R, Vonsattel JP, Troncoso JC, Kril JJ, Kwok JB, Halliday GM, Bird TD, Ince PG, Shaw PJ, Cairns NJ, Morris JC, McLean CA, DeCarli C, Ellis WG, Freeman SH, Frosch MP, Growdon JH, Perl DP, Sano M, Bennett DA, Schneider JA, Beach TG, Reiman EM, Woodruff BK, Cummings J, Vinters HV, Miller CA, Chui HC, Alafuzoff I, Hartikainen P, Seilhean (2010), “Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions.” Nat Genet 42(3):234-9 Details Xiong L, Xuereb JH, Spillantini MG, Patterson K, Hodges JR, Nestor PJ (2010), “Clinical comparison of progressive aphasia associated with Alzheimer versus FTD-spectrum pathology.” J Neurol Neurosurg Psychiatry Details 2009Anderson JM, Patani R, Reynolds R, Nicholas R, Compston A, Spillantini MG, Chandran S (2009), “Evidence for abnormal tau phosphorylation in early aggressive multiple sclerosis.” Acta Neuropathol 117(5):583-9 Details Borroni B, Gardoni F, Parnetti L, Magno L, Malinverno M, Saggese E, Calabresi P, Spillantini MG, Padovani A, Di Luca M (2009), “Pattern of Tau forms in CSF is altered in progressive supranuclear palsy.” Neurobiol Aging 30(1):34-40 Details Bridge KE, Berg N, Adalbert R, Babetto E, Dias T, Spillantini MG, Ribchester RR, Coleman MP (2009), “Late onset distal axonal swelling in YFP-H transgenic mice.” Neurobiol Aging 30(2):309-21 Details Gasparini L, Anthony Crowther R, Martin KR, Berg N, Coleman M, Goedert M, Spillantini MG (2009), “Tau inclusions in retinal ganglion cells of human P301S tau transgenic mice: Effects on axonal viability.” Neurobiol Aging Details Pereira JM, Williams GB, Acosta-Cabronero J, Pengas G, Spillantini MG, Xuereb JH, Hodges JR, Nestor PJ (2009), “Atrophy patterns in histologic vs clinical groupings of frontotemporal lobar degeneration.” Neurology 72(19):1653-60 Details 2008Anderson JM, Hampton DW, Patani R, Pryce G, Crowther RA, Reynolds R, Franklin RJ, Giovannoni G, Compston DA, Baker D, Spillantini MG, Chandran S (2008), “Abnormally phosphorylated tau is associated with neuronal and axonal loss in experimental autoimmune encephalomyelitis and multiple sclerosis.” Brain 131(Pt 7):1736-48 Details Costa C, Belcastro V, Tozzi A, Di Filippo M, Tantucci M, Siliquini S, Autuori A, Picconi B, Spillantini MG, Fedele E, Pittaluga A, Raiteri M, Calabresi P (2008), “Electrophysiology and pharmacology of striatal neuronal dysfunction induced by mitochondrial complex I inhibition.” J Neurosci 28(32):8040-52 Details Delobel P, Lavenir I, Fraser G, Ingram E, Holzer M, Ghetti B, Spillantini MG, Crowther RA, Goedert M (2008), “Analysis of tau phosphorylation and truncation in a mouse model of human tauopathy.” Am J Pathol 172(1):123-31 Details Spina S, Farlow MR, Unverzagt FW, Kareken DA, Murrell JR, Fraser G, Epperson F, Crowther RA, Spillantini MG, Goedert M, Ghetti B (2008), “The tauopathy associated with mutation +3 in intron 10 of Tau: characterization of the MSTD family.” Brain 131(Pt 1):72-89 Details Ye L, Velasco A, Fraser G, Beach TG, Sue L, Osredkar T, Libri V, Spillantini MG, Goedert M, Lockhart A (2008), “In vitro high affinity alpha-synuclein binding sites for the amyloid imaging agent PIB are not matched by binding to Lewy bodies in postmortem human brain.” J Neurochem 105(4):1428-37 Details 2007Goris A, Williams-Gray CH, Clark GR, Foltynie T, Lewis SJ, Brown J, Ban M, Spillantini MG, Compston A, Burn DJ, Chinnery PF, Barker RA, Sawcer SJ (2007), “Tau and alpha-synuclein in susceptibility to, and dementia in, Parkinson's disease.” Ann Neurol 62(2):145-53 Details Lambourne SL, Humby T, Isles AR, Emson PC, Spillantini MG, Wilkinson LS (2007), “Impairments in impulse control in mice transgenic for the human FTDP-17 tauV337M mutation are exacerbated by age.” Hum Mol Genet 16(14):1708-19 Details Michell AW, Tofaris GK, Gossage H, Tyers P, Spillantini MG, Barker RA (2007), “The effect of truncated human alpha-synuclein (1-120) on dopaminergic cells in a transgenic mouse model of Parkinson's disease.” Cell Transplant 16(5):461-74 Details 2006Goedert M, Spillantini MG (2006), “A century of Alzheimer's disease.” Science 314(5800):777-81 Details Goedert M, Spillantini MG (2006), “Frontotemporal lobar degeneration through loss of progranulin function.” Brain 129(Pt 11):2808-10 Details Tofaris GK, O’Connell M, Ghetti B, Humby T, Lambourne L, Gossage H, Emson PC, Wilkinson LS, Goedert M, Spillantini MG (2006), “Pathological changes in dopaminergic neurones in mice transgenic for human a-synuclein (1-120): implications for Lewy body disorders” J Neuroscience 26:3942-3950 2003Tofaris G, Razzaq A, Ghetti B, Lilley K, Spillantini MG (2003), “Ubiquitination of ?-synuclein in Lewy bodies is a pathological event not associated with impairment of proteasome function” Journal of Biological Chemistry 278:44405-44411 1998Spillantini MG, Bird TD, Ghetti B (1998), “Frontotemporal dementia and Parkinsonism linked to chromosome 17: a new group of tauopathies.” Brain Pathol 8(2):387-402 Details Spillantini MG, Crowther RA, Kamphorst W, Heutink P, van Swieten JC (1998), “Tau pathology in two Dutch families with mutations in the microtubule-binding region of tau.” Am J Pathol 153(5):1359-63 Details |