Professor Dame Pamela J Shaw
DBE MBBS MD FRCP FMedSci FAAN FANA FAAAS
Tel: +44 (0)114 22 28714
or +44 (0)114 22 22295
Email: : firstname.lastname@example.org
Medical NHS Secretary: Erica Waines
Telephone: +44 (0)114 2261049
Royal Hallamshire Hospital
United Kingdom, S10 2JF
Academic Secretary: Laura Haslam
Tel: +44 (0)114 22 28714
University of Sheffield
387 Glossop Road
Sheffield S10 2HQ
Professor Shaw graduated in Medicine with 1st Class Honours from the University of Newcastle in 1979. She undertook her MRCP and Specialist Training in Neurology training in Newcastle. In 1988 she was awarded an MD with commendation for her work on the neurological complications of coronary bypass surgery. After an intermediate fellowship award from the Wellcome Trust, she was awarded a Wellcome Senior Fellowship in Clinical Science which she held from 1991 -2000. In 1997 she was appointed Professor of Neurological Medicine at the University of Newcastle and in 2000 was appointed as Professor of Neurology at the University of Sheffield.
As an undergraduate in Newcastle she was awarded the Stephen Scott; Gibb; Mary Gordon; Mona McNaughton and Phillipson Prizes/Scholarships and achieved distinction in all undergraduate examinations.
Professor Shaw is a Clinician Scientist in Neurology, an NIHR Senior Investigator and formerly a Wellcome Senior Clinical Fellow. Supported by long-term programme funding from the Wellcome Trust, she has since 1991 led a major multidisciplinary programme of research investigating genetic, molecular and neurochemical factors underlying neurodegenerative disorders of the human motor system. Her team use robust cellular and in vivo models of neurodegeneration and correlate key findings with disease related changes in the human nervous system. Significant research achievements include:
Professor Shaw’s research is currently funded by the Medical Research Council, NIHR, the Motor Neurone Disease Association, the European Union and biotechnology & pharmaceutical industry partners. Since 1983 she has generated more than £56m in research income.
Professor Shaw’s research is focused on 3 main goals:
Since 1983 she has supervised the research training of > 120 individuals from medicine and science including 45 PhD/MD students.
Principal Funding Sources
Professor Shaw is a member of multiple national and international committees, sits on the editorial board of several journals including Brain and Amyotrophic Lateral Sclerosis and is a reviewer for numerous other journals.
Membership of Editorial Boards
She has been a research advisory panel member for the Wellcome Trust, MNDA, MRC,the Muscular Dystrophy Association the Academy of Medical Sciences, the Acade,my of Scienec Finland and reviews for multiple grant awarding bodies.
Membership of National and International Committees
|Research Team||Current Scientific research team
SITraN PI Scientific Collaborators
Current Clinical Research Team
SITraN PI Clinical Research Collaborators
PUBLICATIONS >425 H-INDEX 82
Selected Recent Publications
Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomized controlled trial. SC Bourke, M Tomlinson, TL Williams, RE Bullock, PJ Shaw*, GJ Gibson* (Joint Senior Authors). Lancet Neurology 5:140-147;2006.
Pathogical TDP-43 distinguishes sporadic ALS from ALS with SOD1 mutations. IRA Mackenzie, EH Bigio, PG Ince, F Geser, M Neumann, NJ Cairns, LK Kwong, MS Forman, J Ravits, H Stewart, A Eisen, L McClusky, HA Kretzschmar, CM Monoranu, R Highley, J Kirby, T Siddique, PJ Shaw, VMY Lee, J Q Trojanowski. Ann Neurol 61:427-435;2007.
Microarray analysis of the cellular pathways involved in the adaptation to and progression of motor neuron injury in the SOD1 G93A mouse model of familial ALS. L Ferraiuolo, PR Heath, H Holden, PR Kasher, J Kirby, PJ Shaw. J Neuroscience 27:9201-9219;2007.
Physical exercise as an exogenous risk factor in motor neurone disease (MND): a review of the evidence. C Moore, CJ McDermott, PJ Shaw. Amyotrophic Lateral Sclerosis 2009;4:1-14.
Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS). LE Cox, L Ferraiuolo, PR Heath, A Higginbottom, H Mortiboys, H Nixon, JA Hartley, A Brockington, CE Burness, SB Wharton, AJ Grierson, PG Ince, J Kirby, PJ Shaw. PloS One 5: e9872 ;2010 (ePub March 24)
Oxidative stress in ALS: key role in motor neuron injury and a therapeutic target. SC Barber, PJ Shaw. Free Rad Biol Med 48:629-641;2010.
Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions. VM Van Deerlin, PMA Sleiman, M Martinez-Lage et al including PJ Shaw Nature Genetics 42:234-239; 2010.
PTEN depletion modulates axon growth and regulates translation of β-actin at the growth cone in motor neurons. K Ning, C Drepper, C Valori, M Wyles, A Higginbottom, T Hermann, PJ Shaw, M Azzouz, M Sendtner. Hum Mol Genet 19:3159-3168;2010.
Systemic delivery of sc AAV9 expressing SMNB prolongs survival in a model of spinal muscular atrophy. CF Valori, K Ning, M Wyles, RJ Mead, AJ Grierson, PJ Shaw, M Azzouz. Science Translational Medicine 2010 Jun9:2:35ra42.
Microarray analysis of the astrocyte transcriptome in the aging brain: relationship to Alzheimer’s pathology and the APOE genotype. JE Simpson, PG Ince, PJ Shaw, PR Heath, R Raman, C Gelsthorpe, L Baxter, G Forster, FE Matthews, C Brayne, SB Wharton on behalf of the MRC Cognitive Function and Ageing Neuropathology Group. Neurobiol Aging 32:1795-1807;2011.
PTEN/AKT pathway linked to motor neuron survival in human SOD1-related amyotrophic lateral sclerosis (ALS). J Kirby*, K Ning*, L Ferraiuolo, PR Heath, A Ismail, S-W Kuo, L Cox, CF Valori, LE Cox, B Sharrack, SB Wharton, PG Ince, PJ Shaw*, M Azzouz*. Brain 134:506-517;2011 (*Equal contribution).
Dysregulation of astrocyte-motor neuron cross-talk in mutant SOD1 related amyotrophic lateral sclerosis. L Ferraiuolo, A Higginbottom, PR. Heath, S Barber, D Greenald, J Kirby & PJ. Shaw. Brain 134:2627-2641; 2011.
Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis. L Ferraiuolo, J Kirby, AJ Grierson, M Sendtner, PJ Shaw. Nature Reviews Neurology 7:616-630; 2011.
Clinico-pathological features in amyotrophic lateral sclerosis with expansions in C9ORF72. J Cooper-Knock*, C Hewitt*, J R Highley*, A Brockington, A Milano, S Man, et al, PG Ince, J Hardy, PJ Shaw. *Equal contribution. Brain 135:751-764;2012.
The natural history of motor neuron disease: assessing the impact of specialist care. T Aridegbe, R Kandler, T Walsh, PJ Shaw*, CJ McDermott*. Equal contribution. Amyotroph Lateral Scler Frontotemporal Degen 2012 (Epub May 29). d.o.i: 10.3109/17482968.2012.690419; PMID:22642305.
Gene expression profiling in human neurodegenerative disease. J Cooper-Knock, J Kirby, L Ferraiuolo, PR Heath, M Rattray, PJ Shaw. Nature Reviews Neurology 8:518-530; 2012.
S[+] Apomorphine is a CNS penetrating activator of the NRF2-ARE pathway with activity in mouse and patient fibroblast models of amyotrophic lateral sclerosis. RJ Mead, A Higginbottom, E Bennett, J Kirby, E Bennett, SC Barber, SP Allen, PR Heath, A Coluccia, A Brancale, AJ Grierson, PJ Shaw. Free Rad Biol Med 61C: 438-452; 2013.
Lithium in patients with Amyotrophic lateral sc lerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial. [Eudract number: 2008-006891-31]. UKMND-LiCALS* Group including PJ Shaw as PI. Lancet Neurology 12:339-345;2013 (EPub Feb 27). d.o.i: 10.1016/S1474-4422(13)700374; PMID:23453347.
Unravelling the enigma of selective vulnerability in neurodegeneration: motor neurons resistant to degeneration in ALS show distinct gene expression characteristics and decreased susceptibility to excitotoxicity. A Brockington, K Ning, PR Heath, E Wood, N Fusi, N Lawrence, PG Ince, SB Wharton, PG Ince, PJ Shaw. Acta Neuropath 125:95-109; 2013.
Whole genome transcriptome analysis identifies indices of fast and slow disease progression in two mouse models of amyotrophic lateral sclerosis. G Nardo, R Iennaco, N Fudi, N Lawrence, M Marino, P Heath, L Ferraiuolo, PJ Shaw**, C Bendotti**. Equal contribution. Brain 136:3305-3332;2013.
A new zebrafish model of SOD1 ALS produced by TILLING replicates key features of the disease and represents a tool for in vivo therapeutic screening. MMJ Da Costa, CE Allen, A Higginbottom, T Ramesh, PJ Shaw*, CJ McDermott*. Equal contribution. Disease Models and Mechanisms 2013 (EPub 2 October). d.o.i: 10.1242/dmm.012013 PMID:24092880. 290.
Early interneuron dysfunction in ALS: Insights from a mutant sod1 zebrafish model. A McGown, A Al Mashadi, N Redhead, A Lyon, CE Beattie, PJ Shaw, T Ramesh. Ann Neurol 73:246-258;2013 (E pub Oct 1 2012). D.o.i: 10.1002/ana.23780. PMID:23281025.
Sequestration of multiple RNA recognition motif proteins by C9ORF72 GGGGCC expanded repeats in amyotrophic laterals sclerosis. M J Walsh, J Cooper-Knock, A Higginbottom, JR Highley, J Bury, M Dickman, M Rattray, PR Heath, M Wyles, S Wharton, PG Ince, S Wilson, J Kirby, GM Hautbergue, PJ Shaw. Brain 137:2040-2051; 2014.
A zebrafish model exemplifies the long pre-clinical period of motor neuron disease. TM Ramesh, PJ Shaw, J McDearmid. J Neurol Neurosurg Psychiatry 85:1288-1289;2014 (EPub Jun 26). PMID 24970908.
Direct conversion of patient fibroblasts demonstrates non-cell autonomous toxicity of astrocytes to motor neurons in familial and sporadic ALS. K Meyer, L Ferraiuolo, CJ Miranda, S Likhite, S McElroy, S Renusch, D Ditsworth, C Lagier-Tourenne, RA Smith, J Ravits, AH Burghes, PJ Shaw, DW Cleveland, SJ Kolb, BK Kaspar. PNAS 111:829-832;2014. PMID: 24379375.
PTEN depletion decreases disease severity and modestly prolongs survival in a mouse model of spinal muscular atrophy. D Little, CF Valori, CA Mutsaers, EJ Bennett, M Wyles, PJ Shaw, TH Gillingwater, M Azzouz, K Ning. Molecular Therapy 2014 (ePub November 5). PMID: 25369768
Exome-wide rare variant analysis identifies TUBA4A mutations associated with familial ALS. BT Smith1, N Ticozzi, C Fallini, A Soragia Gkazi, S Topp, J Kost, E Scotter, P Keagle, J Miller, C Tiloca, C Vance, EW Danielson, C Troakes, C Colombrita, S Al-Sarraj, EA Lewis, A King, D Calini, V Pensato, B Castellotti, J de Belleroche, F Bass, AALM ten Asbroek, KP Kenna, RL McLaughlin, M Polak, S Asress, J Esteban-Pérez, JL Muñoz-Blanco, SLAGEN Consortium, G Lauria, S Duga, S Corti, C Cereda, C Lucia, G Sorarù, O Hardiman, KE Morrison, A Al-Chalabi, H Pall, PJ Shaw, K Talbot, F Taroni, A García-Redondo, Z Wu, JD Glass, C Gellera, A Ratti, V Silani, CE Shaw, JE Landers. Neuron 84:324-331;2014.
Gastrostomy in patients with amyotrophic lateral sclerosis (ProGAS): a prospective cohort study.motor neurone disease. ProGas Study Group including PJ Shaw as Co-Chief Investigator. Lancet Neurology 14:702-709; 2015. PMID:26027943.
Antisense RNA foci in the motor neurons of C9ORF72- ALS are associated with TDP-43 proteinopathy. J Cooper-Knock, A Higginbottom, MJ Stopford, JR Highley, PG Ince, SB Wharton, S Pickering-Brown, J Kirby[, GM Hautbergue, PJ Shaw. Acta Neuropathologica 130:63-75;2015.
ZNStress: A high-throughput drug screening protocol for identification of compounds modulating neuronal stress in the transgenic mutant sod1G93R zebrafish model of amyotrophic lateral sclerosis. A McGown, PJ Shaw, T Ramesh. Molecular Neurodegeneration 2016 (In Press).
The C9orf72 protein interacts with Rab1a and the ULK1 complex to regulate initiation of autophagy. CP Webster, EF Smith, CS Bauer, GM Hautbergue, L Ferraiuolo, M Myszczynska, A Higginbottom, MJ Walsh, A Moller, AJ Whitworth, BK Kaspar, K Meyer, PJ Shaw, AJ Grierson, KJ De Vos. EMBO J 2016;35:1656-1676. PMID: 27334615.
Oligodendrocytes contribute to motor neuron death in ALS via SOD1 dependent mechanism. L Ferraiuolo, K Meyer, T Sherwood, J Vick, S Likhite, AE Frakes, C Miranda, L Braun, PR Heath, R Pineda, CE Beattie, PJ Shaw, C Askwith, DM McTigue, B K Kaspar. PNAS 2016 Sept 29 PMID:27688759.
Long-term physical activity: an exogenous risk factor for sporadic amyotrophic lateral sclerosis. CA Harwood, H Besson, U Ekelund, K Westgate, S Gunstone, S Brage, S Sharpe, NJ Wareham, CJ McDermott, PJ Shaw. Amyotroph Lateral Scler Frontotemporal Degener. 2016 (E pub March 2016).
Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis. W van Rheenen, A Shatunov, AM Dekker, et al. Nature Genetics 2016 48:1043-1048. PMID:27455348.
NEK1 variants confer susceptibility to amyotrophic lateral sclerosis. KP Kenna, PTC van Doormaal, A Dekker, et al. Nature Genetics 2016; 48:1037-1042. PMID: 27455347.
Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. ET Cirulli, BN Lasseigne, S Petrovski, PC Sapp, PA Dion, CS Leblond, J Couthouis, Y‐Fan Lu, Q Wang, BJ Krueger, Z Ren, J Keebler, Y Han, SE Levy, BE Boone, JR Wimbish, LW Jones, AL Jones, JP Carulli, A Day-Williams, JF Staropoli, WW Xin, A Chesi, AR Raphael, D McKenna-Yasek, J Cady, JMBV de Jong, KP Kenna, BN Smith, S Topp, J Miller, A Gkazi, FALS Sequencing Consortium including PJ Shaw, A Al-Chalabi, LH van den Berg, J Veldink, V Silani, N Ticozzi, CE Shaw, RH Baloh, S Appel, E Simpson, C Lagier-Tourenne, SM Pulst, S Gibson, JQ Trojanowski, L Elman, L McCluskey, M Grossman, NA Shneider, WK Chung, JM Ravits, JD Glass, KB Sims, VM Van Deerlin, T Maniatis, SD Hayes, A Ordureau, S Swarup, J Landers, F Baas, AS Allen, RS Bedlack, J Wade Harper, AD Gitler, GA Rouleau, R Brown, MB Harms. Science 347:1436-1441;2015. PMID 25700176.
A randomised controlled trial of the effectiveness of the NeuRx RA/4 Diaphragm Pacing System in patients with respiratory muscle weakness due to motor neurone disease (DiPALS). DiPALS Writing Group; DIPALS Study Group Collaborators including PJ Shaw as Sheffield Centre PI. Lancet Neurology 14:883-892; 2015. PMID:26234554.
C9ORF72 interaction with cofilin modulates actin dynamics in motor neurons. Sivadasan R, Hornburg D, Drepper C, Frank N, Jablonka S, Hansel A, Lojewski X, Sterneckert J, Hermann A, Shaw PJ, Ince PG, Mann M, Meissner F, Sendtner M. Nature Neuroscience. 2016 Oct 10. PMID: 27723745.
C9ORF72 hexanucleotide repeat exerts toxicity in a stable, inducible motor neuronal cell model, which is rescued by partial depletion of Pten. M Stopford, A Higginbottom, G Hautbergue, J Cooper-Knock, P Mulchay, K de Vos, M Azzouz, PR Heath, J Kirby, PJ Shaw. Human Molecular Genetics 2017 (In Press).
A data-driven approach reveals microglial activity to predict pathology and prognosis in amyotrophic lateral sclerosis. J Cooper-Knock, C Green, G Altschuler, W Wei, JJ Bury, PR Heath, M Wyles, C Gelsthorpe, JR Highley, A Pons, K Doyle, K Otero], B Traynor, J Kirby, PJ Shaw*, W Hide*. *Equal contribution. Acta Neuropath Communications 2017 (In Press).