Dr Agnes Nishimura
Lecturer in Neuroscience
SMD/Neuroscience, Surgery and Trauma
QMUL, Blizard Institute
QMUL, Blizard Institute
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
Yang 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 (2024). Reactive astrocytes secrete the chaperone HSPB1 to mediate neuroprotection. American Association for the Advancement of Science (AAAS) Science Advances vol. 10, (12) Shum C, Erin CH, Joseph A, Youn-bok L, Natalia A, Graham C, Siddharthan C, Marc-David R, Christopher ES and Nishimura AL (2024). Mutations in FUS lead to synaptic dysregulation in ALS-iPSC derived neurons. Cell Press Stem Cell Reports 2023
Hedges EC, Cocks G, Shaw CE and Nishimura AL (2023). Generation of an Open-Access Patient-Derived iPSC Biobank for Amyotrophic Lateral Sclerosis Disease Modelling. MDPI Genes vol. 14, (5) 2022
Gomez‐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 (2022). Disruption of ER‐mitochondria tethering and signalling in C9orf72‐associated amyotrophic lateral sclerosis and frontotemporal dementia. Wiley Aging Cell vol. 21, (2) 2021
Gotkine 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 (2021). A recessive S174X mutation in Optineurin causes amyotrophic lateral sclerosis through a loss of function via allele-specific nonsense-mediated decay. Elsevier Neurobiology of Aging vol. 106, 1-6. Gadgil A, Walczak A, Stępień A, Mechtersheimer J, Nishimura AL, Shaw CE, Ruepp M-D and Raczyńska KD (2021). ALS-linked FUS mutants affect the localization of U7 snRNP and replication-dependent histone gene expression in human cells. Springer Nature Scientific Reports vol. 11, (1) Nishimura AL and Arias N (2021). Synaptopathy Mechanisms in ALS Caused by C9orf72 Repeat Expansion. Frontiers Frontiers in Cellular Neuroscience vol. 15, Hedges EC, Topp S, Shaw CE and Nishimura AL (2021). Generation of six induced pluripotent stem cell lines from patients with amyotrophic lateral sclerosis with associated genetic mutations in either FUS or ANXA11. Elsevier Stem Cell Research vol. 52, 2020
Lee 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 (2020). C9orf72 poly GA RAN-translated protein plays a key role in amyotrophic lateral sclerosis via aggregation and toxicity. Oxford University Press (OUP) Human Molecular Genetics vol. 30, (3-4) 318-320. 2018
de 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 (2018). ALS-associated missense and nonsense TBK1 mutations can both cause loss of kinase function. Elsevier Neurobiology of Aging vol. 71, 266.e1-266.e10. Selvaraj 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 (2018). C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable AMPA receptor-mediated excitotoxicity. Springer Nature Nature Communications vol. 9, (1) 2017
Lee 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 (2017). C9orf72 poly GA RAN-translated protein plays a key role in amyotrophic lateral sclerosis via aggregation and toxicity. Oxford University Press (OUP) Human Molecular Genetics vol. 26, (24) 4765-4777. 2016
Chen H-J, Mitchell JC, Novoselov S, Miller J, Nishimura AL, Scotter EL, Vance CA, Cheetham ME and Shaw CE (2016). The heat shock response plays an important role in TDP-43 clearance: evidence for dysfunction in amyotrophic lateral sclerosis. Oxford University Press (OUP) Brain vol. 139, (5) 1417-1432. Hedges EC, Mehler VJ and Nishimura AL (2016). The Use of Stem Cells to Model Amyotrophic Lateral Sclerosis and Frontotemporal Dementia: From Basic Research to Regenerative Medicine. Wiley Stem Cells International vol. 2016, (1) 2014
Nishimura 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 (2014). Allele-Specific Knockdown of ALS-Associated Mutant TDP-43 in Neural Stem Cells Derived from Induced Pluripotent Stem Cells. Public Library of Science (PLoS) PLOS ONE vol. 9, (3) Scotter EL, Vance C, Nishimura AL, Lee Y-B, Chen H-J, Urwin H, Sardone V, Mitchell JC, Rogelj B, Rubinsztein DC and Shaw CE (2014). Differential roles of the ubiquitin proteasome system and autophagy in the clearance of soluble and aggregated TDP-43 species. The Company of Biologists Journal of Cell Science vol. 127, (6) 1263-1278. 2013
Lee 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 (2013). Hexanucleotide Repeats in ALS/FTD Form Length-Dependent RNA Foci, Sequester RNA Binding Proteins, and Are Neurotoxic. Elsevier Cell Reports vol. 5, (5) 1178-1186. Zhang 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 (2013). Downregulation of MicroRNA-9 in iPSC-Derived Neurons of FTD/ALS Patients with TDP-43 Mutations. Public Library of Science (PLoS) PLOS ONE vol. 8, (10) 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 (2013). Comment on “Drug Screening for ALS Using Patient-Specific Induced Pluripotent Stem Cells”. American Association for the Advancement of Science (AAAS) Science Translational Medicine vol. 5, (188) Vance 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 (2013). ALS mutant FUS disrupts nuclear localization and sequesters wild-type FUS within cytoplasmic stress granules. Oxford University Press (OUP) Human Molecular Genetics vol. 22, (13) 2676-2688. Serio 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 (2013). Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy. Proceedings of the National Academy of Sciences Proceedings of the National Academy of Sciences of the United States of America vol. 110, (12) 4697-4702. 2012
Yamazaki 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 (2012). FUS-SMN Protein Interactions Link the Motor Neuron Diseases ALS and SMA. Elsevier Cell Reports vol. 2, (4) 799-806. 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 (2012). Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability. Proceedings of the National Academy of Sciences Proceedings of the National Academy of Sciences of the United States of America vol. 109, (15) 5803-5808. 2011
Hortobágyi T, Troakes C, Nishimura AL, Vance C, van Swieten JC, Seelaar H, King A, Al-Sarraj S, Rogelj B and Shaw CE (2011). Optineurin inclusions occur in a minority of TDP-43 positive ALS and FTLD-TDP cases and are rarely observed in other neurodegenerative disorders. Springer Nature Acta Neuropathologica vol. 121, (4) 519-527. Tollervey 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 (2011). Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Springer Nature Nature Neuroscience vol. 14, (4) 452-458. 2010
Nishimura AL, Župunski V, Troakes C, Kathe C, Fratta P, Howell M, Gallo J, Hortobágyi T, Shaw CE and Rogelj B (2010). Nuclear import impairment causes cytoplasmic trans-activation response DNA-binding protein accumulation and is associated with frontotemporal lobar degeneration. Oxford University Press (OUP) Brain vol. 133, (6) 1763-1771. Funke 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 (2010). The p.P56S mutation in the VAPB gene is not due to a single founder: the first European case. Wiley Clinical Genetics vol. 77, (3) 302-303. 2009
Fukumoto 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 (2009). Sexually dimorphic effect of the Val66Met polymorphism of BDNF on susceptibility to Alzheimer's disease: New data and meta‐analysis. Wiley American Journal of Medical Genetics Part B Neuropsychiatric Genetics vol. 153B, (1) 235-242. Nishimura AL, Oliveira JRM and Zatz M (2009). The human serotonin transporter gene explains why some populations are more optimistic? Springer Nature Molecular Psychiatry vol. 14, (9) 828-828. Vance 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 (2009). Mutations in FUS, an RNA Processing Protein, Cause Familial Amyotrophic Lateral Sclerosis Type 6. American Association for the Advancement of Science (AAAS) Science vol. 323, (5918) 1208-1211. 2008
Oliveira JRM, Nishimura AL, Lemos RR and Zatz M (2008). The Genetics of Alzheimer’s Disease in Brazil: 10 Years of Analysis in a Unique Population. Springer Nature Journal of Molecular Neuroscience vol. 37, (1) 74-79. 2007
Mitne-Neto M, Ramos CRR, Pimenta DC, Luz JS, Nishimura AL, Gonzales FA, Oliveira CC and Zatz M (2007). A mutation in human VAP-B–MSP domain, present in ALS patients, affects the interaction with other cellular proteins. Elsevier Protein Expression and Purification vol. 55, (1) 139-146. 2005
Nishimura AL, Al-Chalabi A and Zatz M (2005). A common founder for amyotrophic lateral sclerosis type 8 (ALS8) in the Brazilian population. Springer Nature Human Genetics vol. 118, (3-4) 499-500. Guindalini C, Scivoletto S, Ferreira RGM, Nishimura A, Zilberman ML, Peluso MM and Zatz M (2005). Association of MAO A polymorphism and alcoholism in Brazilian females. Wolters Kluwer Psychiatric Genetics vol. 15, (2) 141-144. Macedo‐Souza LI, Kok F, Santos S, Amorim SC, Starling A, Nishimura A, Lezirovitz K, Lino AMM and Zatz M (2005). Spastic paraplegia, optic atrophy, and neuropathy is linked to chromosome 11q13. Wiley Annals of Neurology vol. 57, (5) 730-737. Nishimura AL, Guindalini C, Oliveira JRM, Nitrini R, Bahia VS, de Brito-Marques PR, Otto PA and Zatz M (2005). Monoamine oxidase a polymorphism in brazilian patients. Springer Nature Journal of Molecular Neuroscience vol. 27, (2) 213-217. 2004
Nishimura 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 (2004). A Mutation in the Vesicle-Trafficking Protein VAPB Causes Late-Onset Spinal Muscular Atrophy and Amyotrophic Lateral Sclerosis. Elsevier American Journal of Human Genetics vol. 75, (5) 822-831. Nishimura AL, Mitne-Neto M, Silva HCA, Oliveira JRM, Vainzof M and Zatz M (2004). A novel locus for late onset amyotrophic lateral sclerosis/motor neurone disease variant at 20q13. BMJ Journal of Medical Genetics vol. 41, (4) Takata RI, Martins CES, Passosbueno MR, Abe KT, Nishimura AL, Da Silva MD, Monteiro A, Lima MI, Kok F and Zatz M (2004). A new locus for recessive distal spinal muscular atrophy at Xq13.1–q21. BMJ Journal of Medical Genetics vol. 41, (3) Fertuzinhos SMM, Oliveira JRM, Nishimura AL, Pontual D, Carvalho DR, Sougey EB, Otto PA and Zatz M (2004). Analysis of IL-1α, IL-1β, and IL-RA polymorphisms in dysthymia. Springer Nature Journal of Molecular Neuroscience vol. 22, (3) 251-255. Nishimura AL, Oliveira JRM, Mitne-Neto M, Guindalini C, Nitrini R, Bahia VS, de Brito-Marques PR, Otto PA and Zatz M (2004). Lack of association between the brain-derived neurotrophin factor (C-270T) polymorphism and late-onset Alzheimer’s disease (LOAD) in Brazilian patients. Springer Nature Journal of Molecular Neuroscience vol. 22, (3) 257-260. 2001
Schwartzman J, Bernardino A, Nishimura A, Gomes R and Zatz M (2001). Rett Syndrome in a Boy with a 47,XXY Karyotype Confirmed by a Rare Mutation in the MECP2 Gene. Thieme Neuropediatrics vol. 32, (3) 162-164. Nishimura AL, Oliveira JRM, Otto PA, Matioli SR, Brito-Marques PR, Bahia VS, Nitrini R and Zatz M (2001). No evidence of association between the D10S1423 locus and Alzheimer disease in Brazilian patients. Springer Nature Journal of Neural Transmission vol. 108, (3) 305-310. 2000
Nishimura AL, Oliveira JRM, Matioli SR, Brito-Marques PR, Bahia VS, Nitrini R and Zatz M (2000). Analysis of the disease risk locus DXS1047 polymorphism in Brazilian Alzheimer patients. Springer Nature Molecular Psychiatry vol. 5, (5) 563-566. Oliveira 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 (2000). Analysis of the serotonin transporter polymorphism (5-HTTLPR) in Brazilian patients affected by dysthymia, major depression and bipolar disorder. Springer Nature Molecular Psychiatry vol. 5, (4) 348-349. Grants
A stem cell research approach to elucidate the molecular mechanisms underlying heterogeneity of outcome in traumatic brain injuryAgnes Lumi Nishimura, Adina Michael-Titus and Christopher Uff
£74,845 Barts and the London Charity (04-09-2023 - 03-03-2025)