Sheffield Institute for
Translational Neuroscience

Dr Andrew Grierson PhD

Non-clinical Senior Lecturer in Neuroscience


Research Interests

Research in my laboratory concerns identifying the molecular mechanisms underlying the regulation of axonal transport in health and disease. In particular we are investigating the involvement of axonal transport in diseases including motor neurone disease (MND) and hereditary spastic paraplegia (HSP). In addition we are developing and characterising novel vertebrate models of neurodegeneration in zebrafish and mouse. With support from the NC3Rs we are refining the widely used SOD1G93A model of motor neuron disease.

Funding Sources:

 

Current Projects

  • Preclinical testing of HDAC6 inhibition in a zebrafish model of CMT2A (Hereditary Neuropathy Foundation)
  • Investigating the function of the C9ORF72 protein in motor neuron disease (University Studentship)
  • Preclinical assessment of histone deacetylase 6 (HDAC6) inhibition as a therapy for hereditary spastic paraplegia  (Spastic Paraplegia Foundation)
  • ANIMPACT: An ethical, legal and practical perspective on the impact of a new regulatory framework for the scientific use of animals on research and innovation (European Union) 
  • Zebrafish C9orf72 loss of function models of ALS (MND Association)
  • Role of C9ORF72 in proteostasis. (De Vos PI) (Thierry Latran Foundation) ROLE OF MITOCHONDRIA IN C9ORF72-RELATED ALS/MND (De Vos is PI) (MND Association)
  • Preclinical assessment of spastin gene replacement therapy as a treatment for hereditary spastic paraplegia (Spastic Paraplegia Foundation) 

Research Team

  • Channa Hewamadumma (Clinical Fellow)
  • Alifiya Kapasi (PhD Student)
  • Qurat Ul-ain Mahmood (PhD Student)
  • Natalie Rounding (PhD student)
  • Khlood Mehdar (PhD student)
  • Gary Shaw (Research Technician)
  • Katie Adamson (Research Technician)
  • Yolanda Gibson (PhD student)

Research Collaborations

Publications

Recent Publications

Bennett, E. J., Mead, R. J., Azzouz, M., Shaw, P. J., & Grierson, A. J. (2014). Early Detection of Motor Dysfunction in the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis (ALS) Using Home Cage Running Wheels. PLoS ONE, 9(9), e107918. doi:10.1371/journal.pone.0107918

Allen, S. P., Rajan, S., Duffy, L., Mortiboys, H., Higginbottom, A., Grierson, A. J., & Shaw, P. J. (2013). Superoxide dismutase 1 mutation in a cellular model of amyotrophic lateral sclerosis shifts energy generation from oxidative phosphorylation to glycolysis. Neurobiology of Aging. doi:10.1016/j.neurobiolaging.2013.11.025

Hewamadduma, C. A. A., Grierson, A. J., Ma, T. P., Pan, L., Moens, C. B., Ingham, P. W., et al. (2013). Tardbpl splicing rescues motor neuron and axonal development in a mutant tardbp zebrafish. Human Molecular Genetics. doi:10.1093/hmg/ddt082

Hameed, A., Bennett, E., Ciani, B., Hoebers, L. P. C., Milner, R., Lawrie, A., et al. (2013). No evidence for cardiac dysfunction in kif6 mutant mice. PLoS ONE, 8(1), e54636. doi:10.1371/journal.pone.0054636

Chapman, A. L., Bennett, E. J., Ramesh, T. M., De Vos, K. J., & Grierson, A. J. (2013). Axonal Transport Defects in a Mitofusin 2 Loss of Function Model of Charcot-Marie-Tooth Disease in Zebrafish. PLoS ONE, 8(6), e67276. doi:10.1371/journal.pone.0067276

Kasher, P. R., Namavar, Y., van Tijn, P., Fluiter, K., Sizarov, A., Kamermans, M., et al. (2011). Impairment of the tRNA-splicing endonuclease subunit 54 (tsen54) gene causes neurological abnormalities and larval death in zebrafish models of pontocerebellar hypoplasia. Human Molecular Genetics, 20(8), 1574–1584.

Mead, R. J., Bennett, E. J., Kennerley, A. J., Sharp, P., Sunyach, C., Kasher, P., et al. (2011). Optimised and rapid pre-clinical screening in the SOD1(G93A) transgenic mouse model of amyotrophic lateral sclerosis (ALS). PLoS ONE, 6(8), e23244. doi:10.1371/journal.pone.0023244

Valori, C. F., Ning, K., Wyles, M., Mead, R. J., Grierson, A. J., Shaw, P. J., & Azzouz, M. (2010). Systemic delivery of scAAV9 expressing SMN prolongs survival in a model of spinal muscular atrophy. Science Translational Medicine, 2(35), 35ra42. doi:10.1126/scitranslmed.3000830

Kasher PR, De Vos KJ, Wharton SB, Manser C, Bennett EJ, Bingley M, Wood JD, Milner R, McDermott CJ, Miller CC, Shaw PJ, Grierson AJ. Direct evidence for axonal transport defects in a novel mouse model of mutant spastin-induced hereditary spastic paraplegia (HSP) and human HSP patients. J Neurochem. 2009; 110(1):34-44. Abstract

De Vos KJ, Grierson AJ, Ackerley S, Miller CC. Role of axonal transport in neurodegenerative diseases. Annu Rev Neurosci. 2008;31:151-73. Abstract

De Vos KJ, Chapman AL, Tennatn ME, Manser C, Tudor EL, Lau KF, Brownlees J, Ackerley S, Shaw PJ, McLoughlin DM, Shaw CE, Leigh PN, Miller CC, Grierson AJ. Familial amyotrophic lateral sclerosis-linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content. Hum Mol Genet. 2007; 16(22):2720-8. Abstract

Sathasivam S, Grierson AJ, Shaw PJ. Characterization of the caspase cascade in a cell culture model of SOD1-related familial amyotrophic lateral sclerosis: expression activation and therapeutic effects of inhibition. Neuropathol Appl Neurobiol. 2005; 31(5):467-85. Abstract

De Vos KJ, Allan VJ, Grierson AJ, Sheetz MP. Mitochondrial function and actin regulate dynamin-related protein 1-dependent mitochondrial fission. Curr Biol. 2005; 12;15(7):678-83. Abstract

Ackerley S, Grierson AJ (co- first author), Banner S, Perkinton MS, Brownlees J, Byers HL, Ward M, Thornhill P, Hussain K, Waby JS, Anderton BH, Cooper JD, Dingwall C, stress-activated protein kinaseLeigh PN, Shaw CE, Miller CC. p38 phosphorylates neurofilaments and is associated with neurofilament pathology in amyotrophic lateral sclerosis. Mol Cell Neurosci. 2004; 26(2):354-64. Abstract

Saha AR, Hill J, Utton MA, Asuni AA, Ackerley S, Grierson AJ, Miller CC, Davies AM, Buchman VL, Anderton BH, Hanger DP. Parkinson's disease alpha-synuclein mutations exhibit defective axonal
transport in cultured neurons. J Cell Sci. 2004 117(Pt 7):1017-24. Abstract

McDermott CJ, Grierson AJ, Wood JD, Bingley M, Wharton SB, Bushby KM, Shaw PJ. Hereditary spastic paraparesis: disrupted intracellular transport associated with spastin mutation. Ann Neurol. 2003; 54(6):748-59. Abstract

Wharton SB, McDermott CJ, Grierson AJ, Wood JD, Gelsthorpe C, Ince PG, Shaw PJ. The cellular and molecular pathology of the motor system in hereditary spastic paraparesis due to mutation of the spastin gene. J Neuropathol Exp Neurol. 2003; 62(11):1166-77. Abstract

Ackerley S, Thornhill P, Grierson AJ (co-first author), Brownlees J, Anderton BH, Leigh PN, Shaw CE, Miller CC. Neurofilament heavy chain side arm phosphorylation regulates axonal transport of neurofilaments. J Cell Biol. 2003; 161(3):489-95. Abstract

Brownlees J, Ackerley S, Grierson AJ, Jacobsen NJ, Shea K, Anderton BH, Leigh PN, Shaw CE, Miller CC. Charcot-Marie-Tooth disease neurofilament mutations disrupt neurofilament assembly and axonal transport. Hum Mol Genet. 2002; 11(23):2837-44. Abstract

Ackerley S, Grierson AJ (co-first author), Brownlees J, Thornhill P, Anderton BH, Leigh PN, Shaw CE, Miller CC. Glutamate slows axonal transport of neurofilaments in transfected neurons. J Cell Biol. 2000; 150(1):165-76. Abstract

Biography

2009 - present: Senior Lecturer

2001 - 2008: Lecturer, University of Sheffield

1997 - 2001: Postdoctoral Research Associate, Institute of Psychiatry, Kings College London

1994 - 1997: Postdoctoral Research Associate, University of Amsterdam, Netherlands

1991 - 1994: PhD (Molecular Genetics) University of Sheffield

1988 - 1991: BSc (Genetics) University of Sheffield

Contact Details

Department of Neuroscience
Sheffield Institute for Translational Neuroscience
University of Sheffield
Room B25
385a Glossop Road
Sheffield
S10 2HQ

T: +44 (0) 114 22 22277
F: +44 (0) 114 22 22290
E: a.j.grierson@sheffield.ac.uk

Secretary:
Jo Brodie (Mon, Tue)
T: +44 (0) 0114 22 22262
E: j.brodie@sheffield.ac.uk