Yr Athro Nick Allen
Professor
- allennd@cardiff.ac.uk
- +44 (0)29 2087 6196
- Adeilad Syr Martin Evans, Rhodfa'r Amgueddfa, Caerdydd, CF10 3AX
Bywgraffiad
Committees and reviewing
- Executive Board - Cardiff Institute of Tissue Engineering and Repair
Cyhoeddiadau
2022
- Ateaque, S. et al. 2022. Selective activation and down-regulation of Trk receptors by neurotrophins in human neurons co-expressing TrkB and TrkC. Journal of Neurochemistry 161(6), pp. 463-477. (10.1111/jnc.15617)
2021
- Maguire, E. et al. 2021. PIP2 depletion and altered endocytosis caused by expression of Alzheimer's disease-protective variant PLCγ2 R522. EMBO Journal 40(17), article number: e105603. (10.15252/embj.2020105603)
- Goold, R. et al. 2021. FAN1 controls mismatch repair complex assembly via MLH1 retention to stabilize CAG repeat expansion in Huntington's disease. Cell Reports 36(9), article number: 109649. (10.1016/j.celrep.2021.109649)
- Imm, J. et al. 2021. Characterization of DNA methylomic signatures in induced pluripotent stem cells during neuronal differentiation. Frontiers in Cell and Developmental Biology 9, article number: 647981. (10.3389/fcell.2021.647981)
- Steg, L. C. et al. 2021. Novel epigenetic clock for fetal brain development predicts prenatal age for cellular stem cell models and derived neurons. Molecular Brain 14(1), article number: 98. (10.1186/s13041-021-00810-w)
2020
- Comella-Bolla, A. et al. 2020. Human pluripotent stem cell-derived neurons are functionally mature in vitro and integrate into the mouse striatum following transplantation. Molecular Neurobiology 57(6), pp. 2766-2798. (10.1007/s12035-020-01907-4)
- Cook, S. R. et al. 2020. Detrimental effect of zwitterionic buffers on lysosomal homeostasis in cell lines and iPSC-derived neurons. AMRC Open Research 2, article number: 21. (10.12688/amrcopenres.12903.1)
- Smith-Geater, C. et al. 2020. Aberrant development corrected in adult-onset Huntington's disease iPSC-derived neuronal cultures via WNT signaling modulation. Stem Cell Reports 14(3), pp. 406-419. (10.1016/j.stemcr.2020.01.015)
2019
- Baker, E. et al. 2019. Gene-based analysis in HRC imputed genome wide association data identifies three novel genes for Alzheimer’s disease. PLoS ONE 14(7), article number: e0218111. (10.1371/journal.pone.0218111)
- Garcia, V. J., Rushton, D. J., Tom, C. M., Allen, N. D., Kemp, P. J., Svendsen, C. N. and Mattis, V. B. 2019. Huntington's disease patient-derived astrocytes display electrophysiological impairments and reduced neuronal support. Frontiers in Neuroscience 13, article number: 669. (10.3389/fnins.2019.00669)
- Harwood, J. C., Kent, N. A., Allen, N. D. and Harwood, A. J. 2019. Nucleosome dynamics of human iPSC during neural differentiation. EMBO reports 20(6), article number: e46960. (10.15252/embr.201846960)
2018
- Telezhkin, V. et al. 2018. Kv7 channels are upregulated during striatal neuron development and promote maturation of human iPSC-derived neurons. Pflügers Archiv European Journal of Physiology 470(9), pp. 1359-1376. (10.1007/s00424-018-2155-7)
- Merkouris, S. et al. 2018. Fully human agonist antibodies to TrkB using autocrine cell-based selection from a combinatorial antibody library. Proceedings of the National Academy of Sciences 115(30), pp. E7023-E7032. (10.1073/pnas.1806660115)
2017
- Haenseler, W. et al. 2017. A highly efficient human pluripotent stem cell microglia model displays a neuronal-co-culture-specific expression profile and inflammatory response. Stem Cell Reports 8(6), pp. 1727-1742. (10.1016/j.stemcr.2017.05.017)
- Lim, R. G. et al. 2017. Developmental alterations in Huntington's disease neural cells and pharmacological rescue in cells and mice. Nature Neuroscience 20(5), pp. 648-660. (10.1038/nn.4532)
- Bowles, K. R., Stone, T. C., Holmans, P. A., Allen, N. D., Dunnett, S. B. and Jones, L. 2017. SMAD transcription factors are altered in cell models of HD and regulate HTT expression. Cellular Signalling 31, pp. 1-14. (10.1016/j.cellsig.2016.12.005)
2016
- Kemp, P. J. et al. 2016. Improving and accelerating the differentiation and functional maturation of human stem cell-derived neurons: role of extracellular calcium and GABA. The Journal of Physiology 594(22), pp. 6583-6594. (10.1113/JP270655)
- Howard-Jones, R. A., Cheung, O. K. Y., Glen, A., Allen, N. D. and Stephens, P. 2016. Integration-free reprogramming of lamina propria progenitor cells. Journal of Dental Research 95(8), pp. 882-888. (10.1177/0022034516637579)
- Telezhkin, V. et al. 2016. Forced cell-cycle exit and modulation of GABAA, CREB and GSK3β signaling promote functional maturation of induced pluripotent stem cell-derived neurons. American Journal of Physiology - Cell Physiology, article number: ajpcell.00166.2015. (10.1152/ajpcell.00166.2015)
- Gee, H. Y. et al. 2016. FAT1 mutations cause a glomerulotubular nephropathy. Nature Communications 7, article number: 10822. (10.1038/ncomms10822)
- Precious, S. V., Kelly, C. M., Allen, N. D. and Rosser, A. E. 2016. Can manipulation of differentiation conditions eliminate proliferative cells from a population of ES cell-derived forebrain cells?. Neurogenesis 3(1), article number: e1127311. (10.1080/23262133.2015.1127311)
2015
- Straccia, M. et al. 2015. Quantitative high-throughput gene expression profiling of human striatal development to screen stem cell-derived medium spiny neurons. Molecular Therapy - Methods & Clinical Development 2, article number: 15030. (10.1038/mtm.2015.30)
- Celiz, A. D. et al. 2015. Discovery of a novel polymer for human pluripotent stem cell expansion and multilineage differentiation. Advanced Materials 27(27), pp. 4006-4012. (10.1002/adma.201501351)
- Martín-Flores, N. et al. 2015. RTP801 is involved in mutant Huntingtin-induced cell death. Molecular Neurobiology 53(5), pp. 2857-2868. (10.1007/s12035-015-9166-6)
- Jones, A. J. et al. 2015. Evidence for bystander signalling between human trophoblast cells and human embryonic stem cells. Scientific Reports 5, article number: 11694. (10.1038/srep11694)
- Mort, M. E., Carlisle, F., Waite, A., Elliston, L., Allen, N. D., Jones, L. and Hughes, A. 2015. Huntingtin exists as multiple splice forms in human brain. Journal of Huntington's Disease 4(2), pp. 161-171. (10.3233/JHD-150151)
2013
- Rushton, D. J., Mattis, V. B., Svendsen, C. N., Allen, N. D. and Kemp, P. J. 2013. Stimulation of GABA-induced Ca2+ influx enhances maturation of human induced pluripotent stem cell-derived neurons. PLoS ONE 8(11), pp. e81031. (10.1371/journal.pone.0081031)
2012
- Mattis, V. B. et al. 2012. Induced pluripotent stem cells from patients with Huntington's Disease show CAG-repeat-expansion-associated phenotypes. Cell Stem Cell 11(2), pp. 264-278. (10.1016/j.stem.2012.04.027)
- Wray, S. et al. 2012. Creation of an open-access, mutation-defined fibroblast resource for neurological disease research. PLoS ONE 7(8), article number: e43099. (10.1371/journal.pone.0043099)
- Feyeux, M. et al. 2012. Early transcriptional changes linked to naturally occurring Huntington's disease mutations in neural derivatives of human embryonic stem cells. Human Molecular Genetics 21(17), pp. 3883-3895. (10.1093/hmg/dds216)
2011
- Patani, R. et al. 2011. Retinoid-independent motor neurogenesis from human embryonic stem cells reveals a medial columnar ground state. Nature Communications 2, article number: 214. (10.1038/ncomms1216)
- Kelly, C. et al. 2011. Medical terminations of pregnancy: A viable source of tissue for cell replacement therapy for neurodegenerative disorders. Cell Transplantation 20(4), pp. 503-513. (10.3727/096368910X546580)
- Hollins, A. J., Joy, S., Kelly, C. M., Battersby, A. A., Allen, N. D. and Rosser, A. E. 2011. Transplantation of differentiated human embryonic stem cells into a Huntington's Disease model: The challenges of generating neural cells suitable for replacement therapy in neurodegenerative disease. Cell Transplantation 20(4), pp. 563-564.
- Decembrini, S. et al. 2011. Comparative Analysis of the Retinal Potential of Embryonic Stem Cells and Amniotic Fluid-Derived Stem Cells. Stem Cells and Development 20(5), pp. 851-863. (10.1089/scd.2010.0291)
2010
- Ewan, K. B. R. et al. 2010. A useful approach to identify novel small-molecule inhibitors of Wnt-dependent transcription. Cancer Research 70(14), pp. 5963-5973. (10.1158/0008-5472.CAN-10-1028)
- Odeh, H. et al. 2010. Mutations in Grxcr1 Are The Basis for Inner Ear Dysfunction in the Pirouette Mouse. American Journal of Human Genetics 86(2), pp. 148-160. (10.1016/j.ajhg.2010.01.016)
2009
- Wilkinson, W. J., Gadeberg, H., Harrison, A. W. J., Allen, N. D., Riccardi, D. and Kemp, P. J. 2009. Carbon monoxide is a rapid modulator of recombinant and native P2X(2) ligand-gated ion channels. British Journal of Pharmacology 158(3), pp. 862-871. (10.1111/j.1476-5381.2009.00354.x)
- Kelly, C. M. et al. 2009. Neonatal desensitization allows long-term survival of neural xenotransplants without immunosuppression. Nature Methods 6(4), pp. 271-273. (10.1038/nmeth.1308)
- Patani, R., Compston, A., Puddifoot, C., Wyllie, D. J. A., Hardingham, G. E., Allen, N. D. and Chandran, S. 2009. Activin/nodal inhibition alone accelerates highly efficient neural conversion from human embryonic stem cells and imposes a caudal positional identity. PLoS ONE 4(10), article number: e7327. (10.1371/journal.pone.0007327)
- Allen, N. D. and Baird, D. M. 2009. Telomere length maintenance in stem cell populations. Biochimica et Biophysica Acta-Molecular Basis of Disease 1792(4), pp. 324-328. (10.1016/j.bbadis.2009.02.004)
2008
- Bilican, B., Fiore-Heriche, C., Compston, A., Allen, N. D. and Chandran, S. 2008. Induction of Olig2 precursors by FGF involves BMP signalling blockade at the Smad level. PLoS ONE 3(8), article number: e2863. (10.1371/journal.pone.0002863)
- Chandran, S., Caldwell, M. and Allen, N. D. 2008. Introduction: stem cells and brain repair. Philosophical Transactions of the Royal Society B-Biological Sciences 363((1489)), pp. 5-7. (10.1098/rstb.2006.2008)
- Allen, N. D. 2008. Temporal and epigenetic regulation of neurodevelopmental plasticity. Philosophical Transactions of the Royal Society B - Biological Sciences 363(1489), pp. 23-28. (10.1098/rstb.2006.2010)
- Wilkinson, W. J., Hanne, G., Harrison, A. W. J., Allen, N. D., Riccardi, D. and Kemp, P. J. 2008. Carbon monoxide is a rapid modulator of recombinant and native P2X2 ligand-gated ion channels [Abstract]. Purinergic Signalling 4(S1), pp. 26. (10.1007/s11302-008-9116-0)
2007
- Nikoletopoulou, V., Plachta, N., Allen, N. D., Pinto, L., Götz, M. and Barde, Y. 2007. Neurotrophin receptor-mediated death of misspecified neurons generated from embryonic stem cells lacking Pax6. Cell Stem Cell 1(5), pp. 529-540. (10.1016/j.stem.2007.08.011)
- Joannides, A. J. et al. 2007. Environmental signals regulate lineage choice and temporal maturation of neural stem cells from human embryonic stem cells. Brain 130(5), pp. 1263-1275. (10.1093/brain/awm070)
- Battersby, A., Jones, R. D., Lilley, K. S., McFarlane, R. J., Braig, H. R., Allen, N. D. and Wakeman, J. A. 2007. Comparative proteomic analysis reveals differential expression of Hsp25 following the directed differentiation of mouse embryonic stem cells. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1773(2), pp. 147-156. (10.1016/j.bbamcr.2006.08.030)
2006
- Bouhon, I. A., Joannides, A., Kato, H., Chandran, S. and Allen, N. D. 2006. Embryonic stem cell derived neural progenitors display temporal restriction to neural patterning. Stem Cells 24(8), pp. 1908-1913. (10.1634/stemcells.2006-0031)
- Joannides, A., Fiore-Hériché, C., Westmore, K., Caldwell, M., Compston, A., Allen, N. D. and Chandran, S. 2006. Automated mechanical passaging: a novel and efficient method for human embryonic stem cell expansion. Stem Cells 24(2), pp. 230-235. (10.1634/stemcells.2005-0243)
- Joannides, A. J. et al. 2006. A scaleable and defined system for generating neural stem cells from human embryonic stem cells. Stem Cells 25(3), pp. 731-737. (10.1634/stemcells.2006-0562)
- Rosser, A. E. and Allen, N. D. 2006. Help for huntington's: stem cells for neurodegenerative disease. The Biochemist 28, pp. 19-24.
2005
- Bouhon, I. A., Kato, H., Chandran, S. and Allen, N. D. 2005. Neural differentiation of mouse embryonic stem cells in chemically defined medium. Brain Research Bulletin 68(1-2), pp. 62-75. (10.1016/j.brainresbull.2005.08.022)
- Calo, L., Spillantini, M. G., Nicoletti, F. and Allen, N. D. 2005. Nurr1 co-localizes with EphB1 receptors in the developing ventral midbrain, and its expression is enhanced by the EphB1 ligand, ephrinB2. Journal of Neurochemistry 92(2), pp. 235-245. (10.1111/j.1471-4159.2004.02853.x)
2004
- Odeh, H. et al. 2004. Characterization of two transgene insertional mutations at pirouette, a mouse deafness locus. Audiology and Neuro-Otology 9(5), pp. 303. (10.1159/000080701)
- Stopps, M. et al. 2004. Design and application of a novel brain slice system that permits independent electrophysiological recordings from multiple slices. Journal of Neuroscience Methods 132(2), pp. 137-148. (10.1016/j.jneumeth.2003.08.015)
2003
- Chandran, S., Kato, H., Gerreli, D., Compston, A., Svendsen, C. N. and Allen, N. D. 2003. FGF-dependent generation of oligodendrocytes by a hedgehog-independent pathway. Development Vol 13(26), pp. 6599-6609. (10.1242/dev.00871)
- Ciani, L., Patel, A., Allen, N. D. and ffrench-Constant, C. 2003. Mice Lacking the Giant Protocadherin mFAT1 Exhibit Renal Slit Junction Abnormalities and a Partially Penetrant Cyclopia and Anophthalmia Phenotype. Molecular and Cellular Biology 23(10), pp. 3575-3582. (10.1128/MCB.23.10.3575-3582.2003)
- Zou, X., Piper, T. A., Smith, J. A., Allen, N. D., Xian, J. and Bruggemann, M. 2003. Block in development at the pre-B-II to immature B cell stage in mice without lgk and iga light chain. The Journal of Immunology 170(3), pp. 1354-1361.
2002
- Isles, A. R., Baum, M. J., Ma, D., Szeto, A., Keverne, E. B. and Allen, N. D. 2002. A possible role for imprinted genes in inbreeding avoidance and dispersal from the natal area in mice. Proceedings of the Royal Society B: Biological Sciences 269(1492), pp. 665-670. (10.1098/rspb.2001.1911)
- Ma, D., Allen, N. D., Van Bergen, Y. C. H., Jones, C. M. E., Baum, M. J., Keverne, E. B. and Brennan, P. A. 2002. Selective ablation of olfactory receptor neurons without functional impairment of vomeronasal receptor neurons in OMP-ntr transgenic mice. European Journal of Neuroscience 16(12), pp. 2317-2323. (10.1046/j.1460-9568.2002.02303.x)
- Erven, A., Skynner, M. J., Okumura, K., Takebayashi, S., Brown, S. D. M., Steel, K. P. and Allen, N. D. 2002. A novel stereocilia defect in sensory hair cells of the deaf mouse mutant Tasmanian devil. European Journal of Neuroscience 16(8), pp. 1433-1441. (10.1046/j.1460-9568.2002.02213.x)
2001
- Mooslehner, K. A. et al. 2001. Mice with Very Low Expression of the Vesicular Monoamine Transporter 2 Gene Survive into Adulthood: Potential Mouse Model for Parkinsonism. Molecular and Cellular Biology 21(16), pp. 5321-5331. (10.1128/MCB.21.16.5321-5331.2001)
- Isles, A. R., Baum, M. J., Ma, D., Keverne, E. B. and Allen, N. D. 2001. Genetic imprinting: urinary odour preferences in mice. Nature 409(6822), pp. 783-784. (10.1038/35057323)
- Isles, A. R., Baum, M. J., Ma, D., Keverne, E. B. and Allen, N. D. 2001. Urinary odour preferences in mice. Nature 409(6822), pp. 783-784. (10.1038/35057323)
- Cui, W., Allen, N. D., Skynner, M., Gusterson, B. and Clark, A. J. 2001. Inducible ablation of astrocytes shows that these cells are required for neuronal survival in the adult brain. Glia 34(4), pp. 272-282. (10.1002/glia.1061)
- Isles, A. R. et al. 2001. Conditional ablation of neurones in transgenic mice. Journal of Neurobiology 47(3), pp. 183-193. (10.1002/neu.1026)
Current Research
Human IPSC models of neurodegenerative disease
Neurodegenerative diseases are devastating for patients, families and society. Understanding the mechanistic basis of these diseases is fundamental to future drug development and therapeutic intervention. My group works on two diseases – Huntington’s (HD) and Alzheimer’s (AD). HD is an inherited genetic disorder caused by mutation in a single gene called huntingtin (Htt), in contrast AD is a multifactorial disease with a significant degree of risk gene heritability. A major research challenge is to model these diseases, to gain an understanding of disease mechanisms and to build platforms for future drug discovery and testing. To address this challenge my research group has focussed on the development of human cell models of disease. We take advantage of landmark ‘induced pluripotent stem cell technologies’ that ultimately enable disease models to be derived from patients – thereby directly integrating patient genetics into the models.
My group has longstanding expertise in developmental neuroscience and stem cell biology. We harness this expertise to control stem cell differentiation to generate highly defined disease models that comprise the most disease–relevant cells for study. We collaborate extensively working within consortia for HD disease modeling (NINDS/CHDI HD iPS Consortium) and cell therapy (FP7 Repair HD) and for AD in the MRC/Dementia Platform UK (DPUK) stem cell network. For each program we provided expertise in stem cell differentiation, CRISPR-Cas9 genome editing and neurobiology. Our work on HD has led to novel biomarker discovery, provided progressive phenotyping, identified physiological deficits in the human neuronal models and led to engagement with industry to translate platforms for drug discovery.
Current grant support
- MRC
- EU FP7
- GW4
- Wellcome Trust
Collaborators
- Prof Paul Kemp
- Prof Anne Rosser
- Prof Lesley Jones
- Dr Emyr Lloyd Evans
- Prof Adrian Harwood
- Prof James Uney (Bristol)
- Prof Siddharthan Chandran (Edinburgh)
- Prof Richard Wade-Martins (Oxford)
- Prof Nigel Hooper (Manchester)
- Prof Tom Warner (UCL)
- Prof Rick Livesey (Cambridge)
- Prof Leslie Thompson (UCI,USA)
Affiliated staff
Postdocs
- Dr Emma Cope
- Dr Christain Schnell
PhD students
- Aurelien Bunga
- Jasmine Donaldson
- Kimberley Jones
- Nikki Buckner