Dr Gillian Hunter

Personal profile

• 2011–present Postdoctoral Research Fellow, Prof T. Gillingwater Lab, Centre for Integrative Physiology, University of Edinburgh
• 2008–2011 Alzheimer’s Society Postdoctoral Fellowship, Molecular Medicine Centre, University of Edinburgh (with Prof D. Porteous)
• 2006–2008 Alzheimer’s Research Trust Postdoctoral Fellowship, Department of Physiology, Anatomy and Genetics, University of Oxford (with Dr R. Wade-Martins)
• 2005-2006 Alzheimer’s Research Trust Postdoctoral Fellowship, Institute of Psychiatry, Kings College London (with Dr J. Powell)
• 2001-2005 Research Assistant/part-time PhD Dr J. Powell and Prof S. Lovestone, Institute of Psychiatry, Kings College London
• 1999-2000 Industrial work placement student, Astrazeneca Pharmaceuticals, Alderley Edge (with Dr N. Davies)
• 1996-2001 MSci (First Class Hons) Genetics, University of Glasgow

Research

SMA is a prevalent genetic childhood motor neuron disease with an incidence of 1 in 6000 live births. The major pathological hallmark of SMA is the selective degeneration of lower motor neurons in the spinal cord, which leads to progressive muscle denervation, skeletal muscular atrophy and eventual paralysis.

It has recently become clear that SMA is not solely a disease of lower motor neurons and it may in fact be a multi-system disorder (Hamilton and Gillingwater 2013).

Glial cells are crucial to the development, survival and functionality of neurons in both the central and peripheral nervous system and defects in these cells may contribute to neurodegeneration. Using both in vivo and in vitro approaches, we have recently demonstrated that Schwann cells contribute to SMA pathology (Hunter et al, 2014).

Previously, I was involved in a variety of projects using genetic and functional molecular methods to identify novel genetic factors that contributed towards Alzheimer’s disease and non-cognitive ageing.

Funding

• Muscular Dystrophy Campaign
• Alzheimer's Society (personal fellowship)
• Alzheimer's Research Trust (personal fellowship)

Team members

• Professor Tom Gillingwater (PI)
• Ewout Groen
• Ross Jones
• Ines Amorin
• Rachael Powis
• Penelope Boyd
• Hannah Shorrock

Publications

Proitsi P, Lupton MK, Velayudhan L, Hunter G, Newhouse S, Lin K, Fogh I, Tsolaki M, Daniilidou M, Pritchard M, Craig D, Todd S, Johnstone JA, McGuinness B, Kloszewska I, Soininen H, Mecocci P, Vellas B, Passmore PA, Sims R, Williams J, Brayne, C, Alzheimer’s Disease Neuroimaging Intiative, GERAD1 Consortium, Stewart R, Sham P, Lovestone S, Powell JF. Alleles that increase risk for Type 2 diabetes mellitus are not associated with increased risk for Alzheimer’s disease. Neurobiology of Aging, 2014 Dec;35(12):2883.e3-2883.e10

Powis RA, Mutsaers CA, Wishart TM, Hunter G, Wirth B, Gillingwater TH. Increased levels of UCHL1 are a compensatory response to disrupted ubiquitin homeostasis in spinal muscular atrophy and do not represent a viable therapeutic target . Neuropathology and Applied Neurobiology, 2014 Dec;40(7):873-87

Aghamaleky Sarvestany A, Hunter G, Tavendale A, Lamont DJ, Llavero Hurtado M, Graham LC, Wishart TM, Gillingwater TH. Label-free quantitative proteomic profiling identifies disruption of ubiquitin homeostasis as a key driver of schwann cell defects in spinal muscular atrophy. Journal of Proteome Research, 2014 Nov 7;13(11):4546-57

Hunter G, Roche SL, Somers E, Fuller HR, Morris GE, Gillingwater TH. The influence of storage parameters on measurement of survival motor neuron (SMN) protein levels: Implications for pre-clinical studies and clinical trials for spinal muscular atrophy. Neuromuscular Disorders, 2014 Nov;24(11):973-7

Hunter G*, Aghamaleky Sarvestany A*, Roche SL, Syme RC, Gillingwater TH. SMN-dependent intrinsic defects in Schwann cells in mouse models of spinal muscular atrophy. Human Molecular Genetics, 2014 May 1;23(9):2235-50 *denotes joint first author

Wishart TM*, Mutsaers CA*, Riessland M*, Reimer MM*, Hunter G*, Hannam ML, Eaton SL, Fuller HR, Roche SL, Somers E, Morse R, Young PJ, Lamont DJ, Hammerschmidt M, Joshi A, Hohenstein P, Morris GE, Parson SH, Skehel PA, Becker T, Robinson IM, Becker CG, Wirth B, Gillingwater TH. Dysregulation of ubiquitin homeostasis and β-catenin signalling promote spinal muscular atrophy. Journal of Clinical Investigation 2014 Apr 1;124(4):1821-34 *denotes joint first author

Hunter G*, Aghamaleky Sarvestany A*, Roche SL, Symes RC, Gillingwater TH. SMN-dependent intrinsic defects in Schwann cells in mouse models of spinal muscular atrophy. Human Molecular Genetics 2014 May 1;23(9):2235-50 *denotes joint first author

Lupton MK, Proitsi P, Lin K, Hamilton G, Daniilidou M, Tsolaki M, Powell JF. The role of ABCA1 gene sequence variants on risk of Alzheimer’s disease. Journal of Alzheimer’s Disease, 2014 Jan 1;38(4);897-906

Mutsaers CA, Lamont DJ, Hunter G, Wishart TM, Gillingwater TH Label-free proteomics identifies Calreticulin and GRP75/Mortalin as peripherally accessible protein biomarkers for spinal muscular atrophy. Genome Medicine, 2013 Oct 18;5(10):95

Thomson PA, MacIntyre DJ, Hamilton G, Dominiczak A, Smith BH, Morris A, Evans KL, Porteous DJ. Association of DISC1 variants with age of onset in a population- based sample of recurrent major depression. Molecular Psychiatry, 2013 Jul;18(7):745-7

Hamilton G and Gillingwater TH. Spinal muscular atrophy: going beyond the motor neuron. Trends in Molecular Medicine, 2013 Jan;19(1):40-50.

Thomson SR, Nahon JE, Mutsaers CA, Thomson D, Hamilton G, Parson SH, Gillingwater TH. Morphological characteristic of motor neurons do not determine their relative susceptibility to degeneration in a mouse model of spinal muscular atrophy. PLoS One, 2012;7(12)e52605.

Thomson PA, MacIntyre DJ, Hamilton G, Dominiczak A, Smith BH, Morris A, Evans KL, Porteous DJ. Association of DISC1 variants with age of onset in a population- based sample of recurrent major depression. Molecular Psychiatry, 2012 August 7 (E-pub) PMID: 22869032.

Hamilton G, Harris SE, Davies G, Liewald D, Tenesa A, Payton A, Horan MA, Ollier WER, Pendleton N, GERAD1 consortium, Starr JM, Porteous D, Deary IJ. The role of ECE-1 variants in cognition and Alzheimer’s disease. AJMG part B: Neuropsychiatric Genetics, 2012 Sep;159B(6):696-709 . Walker RM, Hill AE, Newman A, Hamilton G, Torrance HS, Anderson SM, Ogawa F, Derizioti P, Nicod J, Vernes SC, Fisher SE, Thomson PA, Porteous DJ, Evans KL. Characterisation of the DISC1 promoter and demonstration of regulation by FOXP2: a mechanism for speech and language dysfunction in psychiatric illness? Human Molecular Genetics 2012 Jul 1;21 (13):2862-72.

Hamilton G, Killick R, GERAD1 consortium, TGen consortium, Lambert J-C, Amouyel P, EADI, Carrasquillo MM, Pankratz VS, Graff-Radford NR, Dickson DW, Petersen RC, Younkin SG, Powell JF, Wade-Martins R. Functional and genetic analysis of haplotypic sequence variation at the nicastrin genomic locus. Neurobiology of Aging 2012 Aug;33(8):1848e.1-1848.e13.

Proitsi P, Lupton MK, Dudbridge F, Tsolaki M, Hamilton G, Daniilidou M, Pritchard M, Lord K, Martin BM, Craig D, Todd S, McGuinness B, Hollingworth P, Harold D, Kloszewska I, Soininen H, Mecocci P, Velas B, Gill M, Lawlor B, Rubinsztein DC, Brayne C, Passmore PA, Williams J, Lovestone S, Powell JF. Alzheimer’s disease and age-related macular degeneration have different genetic models for complement gene variation. Neurobiology of Aging 2012 Aug;33(8):1843e.9-1843e.17.

Hamilton G, Evans KL, MacIntyre DJ, Deary IJ, Dominiczak A, Smith B, Morris A, Porteous DJ, Thomson PA. Alzheimer’s disease risk factor complement 1 receptor is associated with depression. Neuroscience Letters 2012 Feb 21;510(1):6-9.

Hamilton G, Harris SE, Davies G, Starr JM, Porteous D, Deary IJ. Alzheimer’s disease genes are associated with measures of cognitive ageing in the Lothian Birth Cohorts of 1921 and 1936. International Journal Alzheimer’s Disease 2011 Jun 12 (E-pub) PMID: 21766012.

Proitsi P, Hamilton G, Tsolaki M, Lupton M, Daniilidou M, Hollingworth P, Archer N, Foy C, Stylios F, McGuinness B, Todd S, Lawlor B, Gill M, Brayne C, Rubinsztein DC, Owen M, Williams J, Craig D, Passmore P, Lovestone S, Powell JF. A multiple indicators multiple causes (MIMIC) model of behavioural and psychological symptoms in dementia (BPSD). Neurobiology of Aging 2011 Mar;32(3):434-42.

Lupton MK, Proitsi P, Danillidou M, Tsolaki M, Hamilton G, Wroe R, Pritchard M, Lord K, Martin BM, Kloszewska I, Soininen H, Mecocci P, Velas B, Lovestone S, Powell JF. Deep sequencing of the nicastrin gene in pooled DNA, the identification of genetic variants that affect risk of Alzheimer’s disease. PLoS ONE 2011 Feb 25;5(2):e17298.

Proitsi P, Lupton MK, Reeves SJ, Hamilton G, Archer N, Martin BM, Iyegbe C, Hollingworth P, Lawlor B, Gill M, Brayne C, Rubinsztein DC, Owen MJ, Williams J, Lovestone S, Powell J. Association of serotonin and dopamine gene pathways with behavioural subphenotypes in dementia. Neurobiology of Aging 2012 Apr;33(4):791-803.

Adamis D, Lunn M, Martin FC, Treloar A, Gregson N, Hamilton G, MacDonald AJD. Cytokines and IGF-I in delirious and non-delirious acutely ill older medical inpatients. Age and Ageing 2009 May;38 (3):326-32.

Kwok JBJ, Loy CT, Hamilton G, Lau E, Hallup M, Williams J, Owen MJ, Broe GA, Tang N, Lam L, Powell JF, Lovestone S, Schofield PR. Glycogen synthase kinase-3β and Tau Genes Interact in Alzheimer’s disease. Annals of Neurology 2008 Oct;64(4):446-54.

Morgan AR, Hamilton G, Turic D, Jehu L, Harold D, Abraham R, Hollingworth P, Moskvina V, Brayne C, Rubinsztein DC, Lynch A, Lawlor B, Gill M, O’Donovan M, Powell J, Lovestone S, Williams J, Owen MJ. Association analysis of 528 intra-genic SNPs in a region of chromosome 10 linked to late onset Alzheimer's disease. AJMG part B: Neuropsychiatric Genetics 2008 Sep 5;147B(6):727-31.

Proitsi P, Li T, Hamilton G, Di Forti M, Collier D, Killick R, Chen R, Sham P, Murray R, Powell J, Lovestone S. Positional pathway screen of wnt signalling genes in schizophrenia: association with DKK4. Biological Psychiatry 2008 Jan 1; 63(1):13-16.

Hamilton G, Proitsi P, Williams J, O’Donovan M, Owen M, Powell J, Lovestone S. Complement Factor H Y402H polymorphism is not associated with late-onset Azheimer’s disease. Neuromolecular Medicine 2007;9(4):331-4.

Adamis D, Treloar A, Martin FC, Gregson N, Powell J, Hamilton G, MacDonald AJD. 18. APOE and cytokines as biological markers for recovery of prevalent delirium in elderly medical impatients. International Journal of Geriatric Psychiatry 2007 Jul;22(7):688-94.

Hamilton G, Proitsi P, Jehu L, Morgan A, Williams J, O’Donovan MC, Owen MJ, Powell JF, Lovestone S. Candidate Gene Association Study of Insulin Signalling Genes and Alzheimer’s Disease: Evidence for SOS2, PCK1 and PPARγ as Susceptibility Loci. AJMG part B: Neuropsychiatric Genetics 2007 Jun 5;144(4):508-16.

Morgan AR, Turic D, Jehu L, Hamilton G, Hollingworth P, Moskvina V, Jones L, Lovestone S, Brayne C, Rubinsztein DC, Lynch A, Lawlor B, Gill M, O’Donovan MC, Owen MJ, Williams J. Association analysis of 23 positional/functional candidate genes on chromosome 10 with Late Onset Alzheimer’s disease. AJMG part B: Neuropsychiatric Genetics 2007 Mar 20;144B(6):762-770.

Hye A, Lynham S, Thambisetty M, Causevic M, Campbell J, Byers HL, Hooper C, Rijsdijk F, Tabrizi SJ, Banner S, Shaw CE, Foy C, Poppe M, Archer N, Hamilton G, Powell J, Brown RG, Sham P, Ward M, Lovestone S. Proteome-based plasma biomarkers for Alzheimer’s disease. Brain 2006 129:3042-3050.

Hamilton G, Samedi F, Knight J, Archer N, Foy C, Walter S, Turic D, Jehu L, Moore P, Hollingworth P, O’Donovan MC, Williams J, Owen MJ, Lovestone S, Powell JF. Polymorphisms in the phosphate and tensin homolog gene are not associated with late-onset Alzheimer’s disease. Neuroscience Letters 2006 Jun 19:401 (1-2):77-80.

Grupe A, Li Y, Rowland C, Nowotny P, Hinrichs AL, Smemo S, Kauwe JSK, Maxwell TJ, Cherny S, Doil L, Tacey K, van Luchene R, Myers A, Wavrant-De Vrièze F, Kaleem M, Hollingworth P, Jehu L, Foy C, Archer N, Hamilton G, Holmans P, Morris CM, Catanese J, Sninsky J, White TJ, Powell J, Hardy J, O’Donovan M, Lovestone S, Jones L, Morris JC, Thal L, Owen M, Williams J, Goate A. A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease. American Journal Human Genetics 2006 Jan;78(1):78-88.

Deary IJ, Hamilton G, Hayward C, Whalley LJ, Powell J, Starr JM, Lovestone S. Nicastrin gene polymorphisms, cognitive ability level and cognitive ageing. Neuroscience Letters 2005 Jan 10;373(2):110-4.