Dr Agnes Nishimura
Lecturer in Neuroscience
SMD/Neuroscience, Surgery and Trauma, Blizard Institute
Queen Mary University of London
Queen Mary University of London
Research
Neuroscience, iPSC, disease modelling, organoids, Neurodegenerative diseases, Amyotrophic lateral sclerosis
Interests
My research focuses on understanding the disease mechanisms of neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS), Frontotemporal dementia, Alzheimer's disease and traumatic brain injury. My expertise in stem cell research and disease modelling led to the creation of a biobank of inducible pluripotent stem cells from patients with ALS. I am modelling neurodegenerative diseases in a dish using 2D multicellular cultures (neurons, astrocytes and microglia) and 3D organoids and screening for compounds to rescue disease-associated phenotypes. I am interested in molecular pathways involving mitochondrial function, apoptosis, lysosome/autophagy, proteostasis, lipid dysregulation and intracellular transport.Publications
2024
Reactive astrocytes secrete the chaperone HSPB1 to mediate neuroprotectionYang F, Beltran-Lobo P, Sung K, Goldrick C, Croft CL, Nishimura A, Hedges E, Mahiddine F, Troakes C, Golde TE, Perez-Nievas BG, Hanger DP, Noble W and Jimenez-Sanchez M
Science Advances, American Association For The Advancement of Science (Aaas) vol. 10 (12)
20-03-2024
Mutations in FUS lead to synaptic dysregulation in ALS-iPSC derived neuronsShum C, Erin CH, Joseph A, Youn-bok L, Natalia A, Graham C, Siddharthan C, Marc-David R, Christopher ES and Nishimura AL
Stem Cell Reports, Cell Press
18-01-2024
2023
Generation of an Open-Access Patient-Derived iPSC Biobank for Amyotrophic Lateral Sclerosis Disease ModellingHedges EC, Cocks G, Shaw CE and Nishimura AL
Genes, Mdpi vol. 14 (5)
18-05-2023
2022
Disruption of ER‐mitochondria tethering and signalling in C9orf72‐associated amyotrophic lateral sclerosis and frontotemporal dementiaGomez‐Suaga P, Mórotz GM, Markovinovic A, Martín‐Guerrero SM, Preza E, Arias N, Mayl K, Aabdien A, Gesheva V, Nishimura A, Annibali A, Lee Y, Mitchell JC, Wray S, Shaw C, Noble W and Miller CCJ
Aging Cell, Wiley vol. 21 (2)
13-01-2022
2021
A recessive S174X mutation in Optineurin causes amyotrophic lateral sclerosis through a loss of function via allele-specific nonsense-mediated decayGotkine M, de Majo M, Wong CH, Topp SD, Michaelson-Cohen R, Epsztejn-Litman S, Eiges R, Y YL, Kanaan M, Shaked HM, Alahmady N, Vance C, Newhouse SJ, Breen G, Nishimura AL, Shaw CE and Smith BN
Neurobiology of Aging, Elsevier vol. 106, 1-6.
04-06-2021
ALS-linked FUS mutants affect the localization of U7 snRNP and replication-dependent histone gene expression in human cellsGadgil A, Walczak A, Stępień A, Mechtersheimer J, Nishimura AL, Shaw CE, Ruepp M-D and Raczyńska KD
Scientific Reports, Springer Nature vol. 11 (1)
04-06-2021
Synaptopathy Mechanisms in ALS Caused by C9orf72 Repeat ExpansionNishimura AL and Arias N
Frontiers in Cellular Neuroscience, Frontiers vol. 15
01-06-2021
Generation of six induced pluripotent stem cell lines from patients with amyotrophic lateral sclerosis with associated genetic mutations in either FUS or ANXA11Hedges EC, Topp S, Shaw CE and Nishimura AL
Stem Cell Research, Elsevier vol. 52
12-02-2021
2020
C9orf72 poly GA RAN-translated protein plays a key role in amyotrophic lateral sclerosis via aggregation and toxicityLee Y-B, Baskaran P, Gomez-Deza J, Chen H-J, Nishimura AL, Smith BN, Troakes C, Adachi Y, Stepto A, Petrucelli L, Gallo J-M, Hirth F, Rogelj B, Guthrie S and Shaw CE
Human Molecular Genetics, Oxford University Press (Oup) vol. 30 (3-4), 318-320.
04-09-2020
2018
ALS-associated missense and nonsense TBK1 mutations can both cause loss of kinase functionde Majo M, Topp SD, Smith BN, Nishimura AL, Chen H-J, Gkazi AS, Miller J, Wong CH, Vance C, Baas F, Asbroek ALMAT, Kenna KP, Ticozzi N, Redondo AG, Esteban-Pérez J, Tiloca C, Verde F, Duga S, Morrison KE, Shaw PJ, Kirby J, Turner MR, Talbot K, Hardiman O, Glass JD, de Belleroche J, Gellera C, Ratti A, Al-Chalabi A and Brown RH
Neurobiology of Aging, Elsevier vol. 71, 266.e1-266.e10.
25-06-2018
C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable AMPA receptor-mediated excitotoxicitySelvaraj BT, Livesey MR, Zhao C, Gregory JM, James OT, Cleary EM, Chouhan AK, Gane AB, Perkins EM, Dando O, Lillico SG, Lee Y-B, Nishimura AL, Poreci U, Thankamony S, Pray M, Vasistha NA, Magnani D, Borooah S, Burr K, Story D, McCampbell A, Shaw CE, Kind PC, Aitman TJ, Whitelaw CBA, Wilmut I, Smith C, Miles GB and Hardingham GE
Nature Communications, Springer Nature vol. 9 (1)
24-01-2018
2017
C9orf72 poly GA RAN-translated protein plays a key role in amyotrophic lateral sclerosis via aggregation and toxicityLee Y-B, Baskaran P, Gomez-Deza J, Chen H-J, Nishimura AL, Smith BN, Troakes C, Adachi Y, Stepto A, Petrucelli L, Gallo J-M, Hirth F, Rogelj B, Guthrie S and Shaw CE
Human Molecular Genetics, Oxford University Press (Oup) vol. 26 (24), 4765-4777.
13-09-2017
2016
The heat shock response plays an important role in TDP-43 clearance: evidence for dysfunction in amyotrophic lateral sclerosisChen H-J, Mitchell JC, Novoselov S, Miller J, Nishimura AL, Scotter EL, Vance CA, Cheetham ME and Shaw CE
Brain, Oxford University Press (Oup) vol. 139 (5), 1417-1432.
01-03-2016
The Use of Stem Cells to Model Amyotrophic Lateral Sclerosis and Frontotemporal Dementia: From Basic Research to Regenerative MedicineHedges EC, Mehler VJ and Nishimura AL
Stem Cells International, Wiley vol. 2016 (1)
01-01-2016
2014
Allele-Specific Knockdown of ALS-Associated Mutant TDP-43 in Neural Stem Cells Derived from Induced Pluripotent Stem CellsNishimura AL, Shum C, Scotter EL, Abdelgany A, Sardone V, Wright J, Lee Y-B, Chen H-J, Bilican B, Carrasco M, Maniatis T, Chandran S, Rogelj B, Gallo J-M and Shaw CE
Plos One, Public Library of Science (Plos) vol. 9 (3)
20-03-2014
Differential roles of the ubiquitin proteasome system and autophagy in the clearance of soluble and aggregated TDP-43 speciesScotter EL, Vance C, Nishimura AL, Lee Y-B, Chen H-J, Urwin H, Sardone V, Mitchell JC, Rogelj B, Rubinsztein DC and Shaw CE
Journal of Cell Science, The Company of Biologists vol. 127 (6), 1263-1278.
01-01-2014
2013
Hexanucleotide Repeats in ALS/FTD Form Length-Dependent RNA Foci, Sequester RNA Binding Proteins, and Are NeurotoxicLee Y-B, Chen H-J, Peres JN, Gomez-Deza J, Attig J, Štalekar M, Troakes C, Nishimura AL, Scotter EL, Vance C, Adachi Y, Sardone V, Miller JW, Smith BN, Gallo J-M, Ule J, Hirth F, Rogelj B, Houart C and Shaw CE
Cell Reports, Elsevier vol. 5 (5), 1178-1186.
27-11-2013
Downregulation of MicroRNA-9 in iPSC-Derived Neurons of FTD/ALS Patients with TDP-43 MutationsZhang Z, Almeida S, Lu Y, Nishimura AL, Peng L, Sun D, Wu B, Karydas AM, Tartaglia MC, Fong JC, Miller BL, Farese RV, Moore MJ, Shaw CE and Gao F-B
Plos One, Public Library of Science (Plos) vol. 8 (10)
15-10-2013
Comment on “Drug Screening for ALS Using Patient-Specific Induced Pluripotent Stem Cells”Bilican B, Serio A, Barmada SJ, Nishimura AL, Sullivan GJ, Carrasco M, Phatnani HP, Puddifoot CA, Story D, Fletcher J, Park I-H, Friedman BA, Daley GQ, Wyllie DJA, Hardingham GE, Wilmut I, Finkbeiner S, Maniatis T, Shaw CE and Chandran S
Science Translational Medicine, American Association For The Advancement of Science (Aaas) vol. 5 (188)
05-06-2013
ALS mutant FUS disrupts nuclear localization and sequesters wild-type FUS within cytoplasmic stress granulesVance C, Scotter EL, Nishimura AL, Troakes C, Mitchell JC, Kathe C, Urwin H, Manser C, Miller CC, Hortobágyi T, Dragunow M, Rogelj B and Shaw CE
Human Molecular Genetics, Oxford University Press (Oup) vol. 22 (13), 2676-2688.
07-03-2013
Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathySerio A, Bilican B, Barmada SJ, Ando DM, Zhao C, Siller R, Burr K, Haghi G, Story D, Nishimura AL, Carrasco MA, Phatnani HP, Shum C, Wilmut I, Maniatis T, Shaw CE, Finkbeiner S and Chandran S
Proceedings of The National Academy of Sciences of The United States of America, Proceedings of The National Academy of Sciences vol. 110 (12), 4697-4702.
11-02-2013
2012
FUS-SMN Protein Interactions Link the Motor Neuron Diseases ALS and SMAYamazaki T, Chen S, Yu Y, Yan B, Haertlein TC, Carrasco MA, Tapia JC, Zhai B, Das R, Lalancette-Hebert M, Sharma A, Chandran S, Sullivan G, Nishimura AL, Shaw CE, Gygi SP, Shneider NA, Maniatis T and Reed R
Cell Reports, Elsevier vol. 2 (4), 799-806.
27-09-2012
Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerabilityBilican B, Serio A, Barmada SJ, Nishimura AL, Sullivan GJ, Carrasco M, Phatnani HP, Puddifoot CA, Story D, Fletcher J, Park I-H, Friedman BA, Daley GQ, Wyllie DJA, Hardingham GE, Wilmut I, Finkbeiner S, Maniatis T, Shaw CE and Chandran S
Proceedings of The National Academy of Sciences of The United States of America, Proceedings of The National Academy of Sciences vol. 109 (15), 5803-5808.
26-03-2012
2011
Optineurin inclusions occur in a minority of TDP-43 positive ALS and FTLD-TDP cases and are rarely observed in other neurodegenerative disordersHortobágyi T, Troakes C, Nishimura AL, Vance C, van Swieten JC, Seelaar H, King A, Al-Sarraj S, Rogelj B and Shaw CE
Acta Neuropathologica, Springer Nature vol. 121 (4), 519-527.
01-03-2011
Characterizing the RNA targets and position-dependent splicing regulation by TDP-43Tollervey JR, Curk T, Rogelj B, Briese M, Cereda M, Kayikci M, König J, Hortobágyi T, Nishimura AL, Župunski V, Patani R, Chandran S, Rot G, Zupan B, Shaw CE and Ule J
Nature Neuroscience, Springer Nature vol. 14 (4), 452-458.
27-02-2011
2010
Nuclear import impairment causes cytoplasmic trans-activation response DNA-binding protein accumulation and is associated with frontotemporal lobar degenerationNishimura AL, Župunski V, Troakes C, Kathe C, Fratta P, Howell M, Gallo J, Hortobágyi T, Shaw CE and Rogelj B
Brain, Oxford University Press (Oup) vol. 133 (6), 1763-1771.
14-05-2010
The p.P56S mutation in the VAPB gene is not due to a single founder: the first European caseFunke A, Esser M, Krüttgen A, Weis J, Mitne‐Neto M, Lazar M, Nishimura A, Sperfeld A, Trillenberg P, Senderek J, Krasnianski M, Zatz M, Zierz S and Deschauer M
Clinical Genetics, Wiley vol. 77 (3), 302-303.
23-02-2010
2009
Sexually dimorphic effect of the Val66Met polymorphism of BDNF on susceptibility to Alzheimer's disease: New data and meta‐analysisFukumoto N, Fujii T, Combarros O, Kamboh MI, Tsai S, Matsushita S, Nacmias B, Comings DE, Arboleda H, Ingelsson M, Hyman BT, Akatsu H, Grupe A, Nishimura AL, Zatz M, Mattila KM, Rinne J, Goto Y, Asada T, Nakamura S and Kunugi H
American Journal of Medical Genetics Part B Neuropsychiatric Genetics, Wiley vol. 153B (1), 235-242.
21-12-2009
The human serotonin transporter gene explains why some populations are more optimistic?Nishimura AL, Oliveira JRM and Zatz M
Molecular Psychiatry, Springer Nature vol. 14 (9), 828-828.
21-08-2009
Mutations in FUS, an RNA Processing Protein, Cause Familial Amyotrophic Lateral Sclerosis Type 6Vance C, Rogelj B, Hortobágyi T, De Vos KJ, Nishimura AL, Sreedharan J, Hu X, Smith B, Ruddy D, Wright P, Ganesalingam J, Williams KL, Tripathi V, Al-Saraj S, Al-Chalabi A, Leigh PN, Blair IP, Nicholson G, de Belleroche J, Gallo J-M, Miller CC and Shaw CE
Science, American Association For The Advancement of Science (Aaas) vol. 323 (5918), 1208-1211.
27-02-2009
2008
The Genetics of Alzheimer’s Disease in Brazil: 10 Years of Analysis in a Unique PopulationOliveira JRM, Nishimura AL, Lemos RR and Zatz M
Journal of Molecular Neuroscience, Springer Nature vol. 37 (1), 74-79.
08-07-2008
2007
A mutation in human VAP-B–MSP domain, present in ALS patients, affects the interaction with other cellular proteinsMitne-Neto M, Ramos CRR, Pimenta DC, Luz JS, Nishimura AL, Gonzales FA, Oliveira CC and Zatz M
Protein Expression and Purification, Elsevier vol. 55 (1), 139-146.
20-04-2007
2005
A common founder for amyotrophic lateral sclerosis type 8 (ALS8) in the Brazilian populationNishimura AL, Al-Chalabi A and Zatz M
Human Genetics, Springer Nature vol. 118 (3-4), 499-500.
27-09-2005
Association of MAO A polymorphism and alcoholism in Brazilian femalesGuindalini C, Scivoletto S, Ferreira RGM, Nishimura A, Zilberman ML, Peluso MM and Zatz M
Psychiatric Genetics, Wolters Kluwer vol. 15 (2), 141-144.
01-06-2005
Spastic paraplegia, optic atrophy, and neuropathy is linked to chromosome 11q13Macedo‐Souza LI, Kok F, Santos S, Amorim SC, Starling A, Nishimura A, Lezirovitz K, Lino AMM and Zatz M
Annals of Neurology, Wiley vol. 57 (5), 730-737.
25-04-2005
Monoamine oxidase a polymorphism in brazilian patientsNishimura AL, Guindalini C, Oliveira JRM, Nitrini R, Bahia VS, de Brito-Marques PR, Otto PA and Zatz M
Journal of Molecular Neuroscience, Springer Nature vol. 27 (2), 213-217.
01-01-2005
2004
A Mutation in the Vesicle-Trafficking Protein VAPB Causes Late-Onset Spinal Muscular Atrophy and Amyotrophic Lateral SclerosisNishimura AL, Mitne-Neto M, Silva HCA, Richieri-Costa A, Middleton S, Cascio D, Kok F, Oliveira JRM, Gillingwater T, Webb J, Skehel P and Zatz M
American Journal of Human Genetics, Elsevier vol. 75 (5), 822-831.
15-09-2004
A novel locus for late onset amyotrophic lateral sclerosis/motor neurone disease variant at 20q13Nishimura AL, Mitne-Neto M, Silva HCA, Oliveira JRM, Vainzof M and Zatz M
Journal of Medical Genetics, Bmj vol. 41 (4)
01-04-2004
A new locus for recessive distal spinal muscular atrophy at Xq13.1–q21Takata RI, Martins CES, Passosbueno MR, Abe KT, Nishimura AL, Da Silva MD, Monteiro A, Lima MI, Kok F and Zatz M
Journal of Medical Genetics, Bmj vol. 41 (3)
01-03-2004
Analysis of IL-1α, IL-1β, and IL-RA polymorphisms in dysthymiaFertuzinhos SMM, Oliveira JRM, Nishimura AL, Pontual D, Carvalho DR, Sougey EB, Otto PA and Zatz M
Journal of Molecular Neuroscience, Springer Nature vol. 22 (3), 251-255.
01-01-2004
Lack of association between the brain-derived neurotrophin factor (C-270T) polymorphism and late-onset Alzheimer’s disease (LOAD) in Brazilian patientsNishimura AL, Oliveira JRM, Mitne-Neto M, Guindalini C, Nitrini R, Bahia VS, de Brito-Marques PR, Otto PA and Zatz M
Journal of Molecular Neuroscience, Springer Nature vol. 22 (3), 257-260.
01-01-2004
2001
Rett Syndrome in a Boy with a 47,XXY Karyotype Confirmed by a Rare Mutation in the MECP2 GeneSchwartzman J, Bernardino A, Nishimura A, Gomes R and Zatz M
Neuropediatrics, Thieme vol. 32 (3), 162-164.
01-06-2001
No evidence of association between the D10S1423 locus and Alzheimer disease in Brazilian patientsNishimura AL, Oliveira JRM, Otto PA, Matioli SR, Brito-Marques PR, Bahia VS, Nitrini R and Zatz M
Journal of Neural Transmission, Springer Nature vol. 108 (3), 305-310.
01-03-2001
2000
Analysis of the disease risk locus DXS1047 polymorphism in Brazilian Alzheimer patientsNishimura AL, Oliveira JRM, Matioli SR, Brito-Marques PR, Bahia VS, Nitrini R and Zatz M
Molecular Psychiatry, Springer Nature vol. 5 (5), 563-566.
01-09-2000
Analysis of the serotonin transporter polymorphism (5-HTTLPR) in Brazilian patients affected by dysthymia, major depression and bipolar disorderOliveira JRM, Carvalho DR, Pontual D, Gallindo RM, Sougey EB, Gentil V, Lafer B, Maia LGS, Morais MA, Matioli S, Vallada H, Moreno RA, Nishimura A, Otto PA, Passos-Bueno MR and Zatz M
Molecular Psychiatry, Springer Nature vol. 5 (4), 348-349.
30-06-2000
Grants
Investigating lipid dysregulation in ALS derived stem cell linesAgnes Nishimura
£254,101 MNDA Motor Neurone Disease Association
01-09-2024 - 31-08-2027
A stem cell research approach to elucidate the molecular mechanisms underlying heterogeneity of outcome in traumatic brain injuryAgnes Nishimura, Adina Michael-Titus and Christopher Uff
£74,845 Barts and the London Charity
04-09-2023 - 03-03-2025