Professor Pamela J Shaw MBBS MD FRCP
Academic Neurology Unit
Department of Neuroscience
Sheffield Institute of Translational Neuroscience
University of Sheffield
385a Glossop Road
Sheffield
S10 2HQ
Tel: +44 (0)114 22 22260
Fax: +44 (0)114 22 22292
Email: : pamela.shaw@sheffield.ac.uk
Academic Secretary: Lorraine Henery
Tel: +44 (0)114 2222260
Email: L.Henery@sheffield.ac.uk
Clinical Secretary: Lynn Stewart
Tel: +44 (0)114 271 3188
Professor of Neurology and Head of Neuroscience Department, University of Sheffield 2000 -present
Director of Sheffield Care and Research Centre for Motor Neuron Disorders 2002 -present
Director of the Sheffield Institute of Translational Neuroscience 2010
Consultant Neurologist Sheffield Teaching Hospitals NHS Foundation Trust 2000- present
Previous positions
1997-2000 Wellcome Senior Research Fellow in Clinical Science and Professor of Neurological Medicine, University of Newcastle upon Tyne
1991-1997 Wellcome Senior Research Fellow in Clinical Science and Honorary Consultant/Senior Lecturer in Neurology, University of Newcastle upon Tyne.
Postgraduate appointments and awards
• 2010 Yorkshire and Humber Deanery Academic Clinical Fellows research presentation prize to my MRC CDBG Clinical Training Fellow Dr Channa Hewamadduma
• 2009 Association of British Neurologists Undergraduate prize awarded to my BMedSci student Ms Elizabeth Wood.
• 2007 The International ALS/MND Forbes Norris Award for excellence in research and compassion in clinical care
• 2007 Fellowship of the Academy of Medical Sciences
• 2007 Spinoza Visiting Professorship, University of Amsterdam
• 2006 Royal College of Physicians Jean Hunter Prize for research into nervous disorders
• 2004 Invited Fellowship of the American Neurological Association
• 2001 Association of British Neurologists Sir Charles Symonds Prize awarded to my research student Dr Stephen Bourke
• 2001 Wellcome Trust Prize studentship final year prize to my PhD student Fiona Menzies
• 2001 American Academy of Neurology and ALS Association Sheila Essey Award for outstanding research contribution in amyotrophic lateral sclerosis/ motor neurone disease
• 2000 Hong Kong Neurological Association Li Po Shan/ Dr Vincent Liu visiting Professorship
• 1997 Invited Fellowship of the American Academy of Neurology
• 1996 Renewal of Wellcome Senior Fellowship in Clinical Science
• 1996 Association of British Neurologists Sir Charles Symonds Prize awarded to my research student Dr Timothy Williams
• 1995 British Medical Association Vera Down Award
• 1992 Poster Research prize at the Third International Symposium on ALS/MND
• 1991 Award of Wellcome Senior Fellowship in Clinical Science
• 1991 Association of British Neurologists Sir Charles Symonds Prize
• 1990 North of England Neurological Association Liversedge Research Prize
• 1985 Northern Regional Health Authority David Dickson Research Prize
• 1985 Association of Physicians UK Dewar Research Prize
• 1985 British Cardiac Society Young Investigator of the Year award
Membership of National and International Committees
• Member of the Executive Committee of the Association of Physicians of Great Britain and Ireland from 1996 to 1999.
• Member of the Motor Neurone Disease Research Advisory Panel from 1993 to 1997.
• Member of the Association of British Neurologists Clinical Research and Academic Committee from 1998-2007.
• Guarantor of the Brain Trust from 1998-2010.
• Advisor to the Department of Health Medicines Control Agency/ Committee on Safety of Medicines from 1997.
• Wellcome Trust / Irish Health Board New Blood Fellowship panel from 1998 to 2000.
• External assessor for Parkinson´s Disease Society 2000.
• Medical Advisor to the Motor Neurone Disease Association from 2000.
• Member of the Neurosciences subpanel for the 2001 UK Universities Research Assessment Exercise.
• Member of the Medical Research Society Committee from 2001.
• Invited expert participant in the NICE panel for the evaluation of riluzole therapy.
• Member of Council for the Association of British Neurologists from 2001 -2007.
• Chairman for the Association of British Neurologists Clinical Research and Academic Committee 2001 -2007.
• Member of the Wellcome Trust Neurosciences Panel from October 2001 -2004.
• Member of Meetings Subcommittee of the Association of British Neurologists from 2001-2003.
• Chairman of the ALS/MND International Scientific Programme Committee from 2004 -2010.
• World Federation of Neurology Working Group on Therapeutic Trials in ALS/MND from 1996.
• Secretary to the European ALS Study Group from 1997 to 2000.
• Member of the European Neurological Society Scientific Committee on motor neurone disease from 1998.
• Coordinator of the Molecular/ Cell Biology Section of the European Familial ALS Group from 1997 to 2000.
• Novartis ALS/MND advisory board 2002.
• Steering committee International MND trial ONO Pharmaceuticals 2002.
• Invited external assessor Neuroscience review panels, University of Glasgow and Imperial College London 2003.
• Member of organising scientific panel for the European Federation of Neurological Societies (EFNS) 2004 -2006
• Member of the scientific panel for the International Congress on Neuromuscular disorders 2004 –2006.
• Member of the UK Medical Research Council College of Experts from 2005-2010.
• Member of the Muscular Dystrophy Campaign Research Advisory Panel from 2004-2007.
• Medical advisor to Oxford Biomedica from 2005-2009.
• Member of editorial boards of Muscle and Nerve, Amyotrophic Lateral Sclerosis and Brain.
• Member of HEFCE Senior Lectureship awards panel from 2006 -2009.
• Associate Director of the Dementia and Neurodegenerative Diseases (DeNDRoN) UK Clinical Research Network from 2004.
• Chair of the DeNDRoN Clinical Studies Group for Motor Neuron Disorders from 2004.
• Member of UKCRN Experimental Medicine Committee 2007-2009.
• Member of the Academy of Medical Sciences Fellowship Panel from 2007-2010.
• Member of the Academy of Medical Sciences Clinical Academic Training Panel from 2008-2009.
• Wellcome Trust / Academy of Medical Sciences New Lecturer Awards panel from 2009-2010.
• UKCRC/ MRC Brain Bank Strategy Advisory Committee 2007 – 2008.
• Member of MRC strategic group for neurodegeneration 2008.
Membership of Editorial Boards
• Muscle and Nerve
• Editorial Panel for Research Frontiers in Science, British Medical Journal.
• Editorial board of Amyotrophic lateral sclerosis
• Editorial Board of Brain
Principal Funding Sources
• The Wellcome Trust
• The Motor Neurone Disease Association
• The Medical Research Council
• NIHR
• European Union
Research income since 1983 >£44m.
Members of Research Group
Scientific research team
Clare Wood-Allum
Alice Brockington
Channa Hewamadduma
Laura Ferraiuolo
Rohini Raman
Akaterini Nanou
Robin Highley
Emily Goodall
Marc da Costa
Adrian Higginbottom
Richard Mead
Paul Heath
Judith Hartley
Laura Cox
Chiara Valori
Paul Sharp
Jonathan Cooper
Chris Hewitt
Lynn Duffy
Scott Allen
Giovanni Nardo
Joanne Bury
Neelam Patel
James Alix
Ellen Bennett
Sandy Rajan
Clinical research team
Chris McDermott
Clare Wood-Allum
Alice Brockington
Channa Hewamadduma
Ceryl Harwood
Hannah Hollinger
Theresa Walsh
Alison Proctor
Melanie Fox
Alison Proctor
Muhammad Rafiq
Susan Thompson
Susan Gunstone
Susie Crawford
Haris Stavroulakis
Tomi Aridegbe
Daniel Blackburn
Research
The Sheffield Institute of Translational Neuroscience, established as part of a major strategic initiative within the University of Sheffield is well-placed to harness the revolutionary developments in biomedical science for the benefit of patients with neurodegenerative disease. The major goal of my group is to elucidate the functioning of motor neurones in health and disease and to translate these basic science findings into health benefits for patients afflicted with degenerative motor system disorders.
My research group consists of a multidisciplinary team of basic and clinical scientists investigating molecular mechanisms of neurodegeneration in disorders of the human motor system, particularly motor neurone disease (MND), spinal muscular atrophy and hereditary spastic paraparesis (HSP). The Neurology group is closely linked with Neuropathology, headed by Professor Paul Ince. The research resources underpinning this programme include clinical material (Biobanks of DNA, blood RNA, CSF, fibroblasts and CNS tissue donated by patients for research); and in vitro and in vivo experimental models employed to investigate molecular mechanisms of motor neurone injury including genetic perturbations, oxidative stress, mitochondrial dysfunction, and disorders of RNA processing.
Major research goals
My research is focused on 3 main goals: 1. To understand the function of motor neurons in health and disease and to translate basic science findings into health benefits for patients with degenerative motor system disorders. 2. To provide excellent clinical care for patients with motor system disorders, at all disease stages incorporating: multidisciplinary team working, evidence based standards of care for symptomatic management, and evaluation of new neuroprotective therapies. 3. To foster excellent training for clinical and scientific junior staff with the aim of ensuring high standards of future care and linking new developments in medical science firmly to the needs of patients with neurological disorders. Since 1983 I have supervised the research training of 103 individuals from medicine and science including 30 PhD/MD students.
Main Research Achievements
Early research achievements included the first detailed study of neurological complications of coronary artery bypass (CABG) surgery, together with evaluation of causative factors, functional impact and prognosis for recovery. This comprehensive documentation of the spectrum of peri-operative neurological complications was instrumental in promoting the development and evaluation of new neuroprotective strategies which have been successful in reducing post-operative morbidity.
Since 1991, I have led a programme of research investigating the genetic, molecular and neurochemical factors underlying neurodegenerative disorders of the human motor system. In all of these areas significant novel insights into motor neuron degeneration have been discovered. My group have described new aspects of the molecular pathology of motor system disorders, including the presence of hyaline conglomerate neurofilamentous inclusions in SOD1 related familial motor neuron disease (MND); and characteristic molecular pathological features of TDP34 inclusions in subtypes of ALS; and the presence of novel cortical pathology, motor neuron cytopathology and defects of microtubule based intracellular transport in spastin related hereditary spastic paraplegia (HSP). My team were amongst the first to describe neurochemical abnormalities in the CNS of human MND patients including: perturbations in free radical detoxifying systems; the presence of oxidative damage to proteins and a motor neuron specific decrease in complex IV of the mitochondrial respiratory chain. In genetic studies we have made unique contributions in correlating genetic alterations to CNS pathology in both MND and HSP and have uncovered new genetic subtypes of MND (associated with mitochondrial tRNA and CHMP2B mutations). We have contributed to collaborative efforts in genome wide association studies which have identified important loci for frontotemporal lobar degeneration (7p --)and for sporadic ALS (9p21).
My research team has been one of the major groups world-wide contributing new insights into the emerging concept that glutamatergic toxicity contributes to motor neuron injury in MND including autoradiographic, immunohistochemical and in situ hybridisation studies indicating altered expression of glutamate receptors and re-uptake transporters in MND and perturbations of CSF glutamate levels in a subset of patients. This body of work contributed to the emergence of the anti-glutamate agent riluzole as a neuroprotective agent in the clinical management of MND, and to the award of the Sir Charles Symonds research prize by the Association of British Neurologists. My group has described several cell specific features of human motor neurons which may account for selective vulnerability to neurodegeneration including: the low expression of calcium binding proteins and the low expression of the GluR2 AMPA receptor subunit, both important components of susceptibility to glutamatergic toxicity. Recent work has identified key differences in the transcriptome of motor neurons which are vulnerable and resistant to the disease process in MND.
By establishing robust cellular models and correlating key findings with in vivo models and human CNS tissue, my team has been at the forefront of research elucidating the molecular pathophysiology of motor neuron injury associated with mutations in Cu/Zn superoxide dismutase (SOD1). This work has been recognised by the award of the Sheila Essey Prize by the American Academy of Neurology. Key findings have demonstrated that motor neuronal cells expressing mutant SOD1 have: 1) Biochemical changes reflecting an increased tendency to apoptosis including increased expression of cleaved caspase 9 and annexin V staining on the cell surface; 2) An increased tendency to cell death by apoptosis when oxidatively stressed; 3) Altered intracellular handling and extracellular release of superoxide and nitric oxide free radical species; 4) Altered regulation, at both mRNA and protein level of specific cytoskeletal components; 5) The development of morphologically abnormal mitochondria, with impaired activity of complexes II and IV of the mitochondrial respiratory chain and impaired cellular bioenergetic status. 6) Alteration in the motor neuron transcriptome and proteome indicating biochemical pathways specifically perturbed by mutant SOD1 which are potentially amenable to therapeutic manipulation. This has allowed us to develop new small molecule and gene therapy candidate therapeutic approaches for patients using staged screening programmes in cellular and other experimental model systems.
Significant contributions from patient based clinical research include the identification and introduction into clinical practice of riluzole as a neuroprotective agent in motor neuron disease and evaluation of further potential neuroprotective therapies. I instigated and directed a clinical research programme to evaluate the effects of non-invasive ventilation in MND patients with neuromuscular respiratory failure. This work has shown a dramatic benefit of NIV on both survival and quality of life, an outcome which has changed clinical practice in the UK and overseas and has resulted in the publication of a NICE clinical practice guideline.
Current research interests include:
- Elucidation of molecular mechanisms of motor neuron degeneration using cellular and in vivo models of genetic subtypes of disease. Particular effort is focused on oxidative stress, mitochondrial dysfunction and dysregulation of RNA processing.
- Application of microarray and proteomic analysis, together with laser capture microdissection of single neuronal populations to identify pathways involved in the different stages of motor neuron injury.
- Identification of novel therapeutic approaches to motor neuron degeneration using cellular
and in vivo models, with staged screening of small molecule and gene therapy neuroprotective agents. - Identification of biomarkers of subtypes of MND using gene expression profiling of peripheral tissues and microdissected motor neurons.
- Identification of genetic and environmental factors predisposing to familial and sporadic
MND, including evaluation of the role of physical activity. - The role of glial cells as contributors to the propagation of motor neuron injury.
Evaluation of respiratory support measures on survival and quality of life in MND, including non-invasive ventilation, the role of cough assist devices and evaluation of diaphragmatic pacing. - Therapeutic trials of novel neuroprotective agents (recent trials Exonhit pentoxifylline; ONO 2506; copaxone; ONO 2506 in early onset patients; TRO19622; lithium.
- Hereditary spastic paraparesis – genetics; genotype-phenotype correlations and
investigation of the effects of relevant mutations in experimental models of disease.
Selected Publications
Mutant SOD1 alters the motor neurone transcriptome: implications for familial amyotrophic lateral sclerosis. J Kirby, PR Heath, S Allen, E Halligan, C A Loynes, C Wood-Allum, H Holden, J Lunec, PJ Shaw. Brain 128:1686-1706;2005.
Apoptosis in amyotrophic lateral sclerosis – what is the evidence. S Sathasivam, PJ Shaw. Lancet Neurology 4:500-509;2005.
Molecular and cellular pathways of neurodegeneration in motor neurone disease (MND). PJ Shaw. J Neurol Neurosurg Psychiatry 76:1046-1057;2005.
Motor neurone disease (MND) phenotype in a patient with a mitochondrial tRNA (Ile) mutation. GM Borthwock, RW Taylor, T Walls, K Tonsca, GA Taylor, PJ Shaw, PG Ince, DM Turnbull. Ann Neurol 59:570-574;2006.
Handbook of Clinical Neurology Series 3rd Edition. Motor Neuron Disorders. Editors Andrew Eisen, PJ Shaw. Elsevier, 2007.
The microtubule severing protein spastin is essential for motor axon outgrowth in the zebrafish embryo. JD Wood, JA Landers,M Bingley, CJ McDermott, V Thomas McArthur, LJ Gleadall, PJ Shaw, VT Cunliffe. Human Molecular Genetics 15:2763-2771;2006.
Impairment of mitochondrial anti-oxidant defence in SOD1related motor neuron injury and amelioration by ebselen. C Wood Allum, SC Barber, J Kirby, P Heath, H Holden, S Allen, T Beaujeux, SHE Alexson, PG Ince, PJ Shaw. Brain 129:1693-1709;2006.
Expression of vascular endothelial growth factor (VEGF) and its receptors in the nervous sytem in ALS. A Brockington, SB Wharton, M Fernando, CH Gelsthorpe, L Baxter, PG Ince, CE Lewis, PJ Shaw. J Neuropathol Exp Neurol
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.
ALS phenotypes are associated with mutations in CHMP2B (charged multivescicular body protein 2B) N Parkinson, PG Ince, MO Smith, R Highley, G Skibinsji, P Andersen, KE Morrison, HS Pall, O Hardiman, J Collinge, PJ Shaw*, EMC Fisher* (Joint Senior authors). Neurology 67:1074-1077; 2006.
Microglia, mutant SOD1 and motor neurons: life and death in a bad neighbourhood. P Monk, PJ Shaw. Nature Medicine 12:885-887;2006.
Culture adaptation of human embryonic stem cells in vitro and stem cell oncogenesis in vivo. D Baker, NJ Harrison, E Maltby, K Smith, HD Moore, PJ Shaw, P Heath, H Holden, , PW Andrews. Nature Biotechnology 25:207-215;2007.
Mutations in VAPB are not associated with sporadic amyotrophic lateral sclerosis. J Kirby*, CAA Hewamadduma*, JA Hartley, HC Nixon, H Evans, RR Wadhwa, C Kershaw, PG Ince, PJ Shaw. Neurology 68:1951-1953;2007.
Linkage to a known gene, but no mutation identified: comprehensive re-analysis of SPG4 HSP pedigrees reveals large deletions as the sole cause. C Beetz, S Zucher, A Ashgley-Koch, M Auer-Grumbach, P Byrne, PF Chinnery, M Hutchinson, CK McDermott, IA Meyer, AOH Nygren, M Pericak-Vance, A Pyle, GA Rouleau, J Schickel, PJ Shaw, T Deufel. Human Mutation 28: 739-740; 2007.
VEGF counteracts the loss of activated Akt preceding motoneuron degeneration in ALS. M Dewil, D Kiraly, R Sciot, PJ Shaw, PG Ince, W Robberecht, L van den Bosch. Neuropathol Appl Neurobiol 33:499-509;2007.
Large scale pathways based association study in amyotrophic lateral sclerosis. D Kasperavicute, ME Weale, KV Shianna, PF Sullivan, CL Simpson, VK Hansen, MR Turner, A l Chalabi, HS Pall, EF Goodall, KE Morrison, RW Orrell, M Bech, S Jabanka, M sendtner, A Brockington, PG Ince, J Hartley, H Nixon, PJ Shaw, G Schiavo, NW Wood, DB Goldstein, EMC Fisher. Brain 130:2292-2301;2007.
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.
Familial amyotrophic lateral sclerosis –linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondrial content. KJ de Vos, A Chapman M Tennant, , C Manser, , E Tudor, KF Lau, J Brownlees, S Ackerley, PJ Shaw, DM McLoughlin, PN Leigh, CCJ Miller, AJ Grierson. Hum Mol Genet 16:2720-2728;2007.
Diagnosis and management of motor neurone disease. CJ McDermott, PJ Shaw. British Medical Journal 336:658-662; 2008.
The motor neuron diseases. PJ Shaw. In: Brain´s Diseases of the Nervous System 12th Edition (Editor: M Donaghy). Chapter 23. 2009.
Heat shock protein 60 (HSP60) is a rare cause of hereditary spastic paraplegia, but may act as a genetic modifier. CAA Hewamadduma, J Kirby, C kershaw, A Dalton, J Martindale, CJ McDermott, PJ Shaw. Neurology 70:1717-1718;2008.
Astrocyte origin, function and role in motor neuron disease. A future therapeutic target? D Blackburn, S Sargsyan, P Monk, PJ Shaw. Glia 57:1251- 1264;2009.
New pedigrees and novel mutation expand the phenotype of REEP1 associated hereditary spastic paraplegia (HSP). CAA Hewamadduma, CJ McDermott, J Kirby, AJ Grierson, M Panayi, A Dalton, YA Rajabally, PJ Shaw. Neurogenetics 10:105-110;2009.
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 4:1-14; 2009.
Transcriptional response of the neuromuscular system to exercise training: and potential implications for amyotrophic lateral sclerosis. L Ferraiuolo, JP de Bono, PR Heath, H Holden, P Kasher, KM Channon, J Kirby, PJ Shaw. J Neurochem 109:1714-1724;2009.
An in vitro screening cascade for anti-oxidant drugs in motor neuron disease models. SC Barber, A Higginbottom, RJ Mead, S Barber, PJ Shaw. Free Radical Biology and Medicine 46:1127-1138;2009.
Direct evidence for axonal transport defects in a novel mouse model of mutant-spastin- induced hereditary spastic paraplegia (HSP) and in human HSP patients. PR Kasher, KF De Vos, SB Wharton, C Manser, EJ Bennett, M Bingley, JD Wood, R Milner, CJ McDermott, CCJ Miller, PJ Shaw*, AJ Grierson*. J Neurochem 110:34-44;2009. * Joint senior authors.
Microarray RNA expression analysis of cerebral white matter lesions reveals changes in multiple functional pathways. JE Simpson, O Hosny El-Sayed, SB Wharton, PR Heath, H Holden, MS Fernando, F Matthews, G Forster, JT O´Brien, MD Barber, RN Kalaria, C Brayne, PJ Shaw, CE Lewis, PG Ince on behalf of the MRC Cognitive Function and Ageing Study Neuropathology Group. Stroke 2009;40:369-375.
Mutant SOD1 G93A microglia have an inflammatory phenotype and elevated production of MCP1. SA Sargsyan, DJ Blackburn, SC Barber, PN Monk, PJ Shaw. Neuroreport 20:1450-1455;2009.
Pattern of spread and prognosis in lower limb onset ALS. MR Turner, A Brockington, J Scaber, H Hollinger, R Marsden, PJ Shaw, K Talbot. Amyotrophic Lateral Sclerosis 11:369-373;2010.
Oxidative stress in ALS: key role in motor neuron injury and a therapeutic target. SC Barber, PJ Shaw. Free Rad Biol Med 2010;48:629-641.
Broad clinical phenotypes associated with TAR-DNA binding protein (TARD-BP) mutations in amyotrophic lateral sclerosis. J Kirby, EF Goodall, W Smith, R Masanzu, JA Hartley, R Hibberd, HC Nixon, S Wharton, KE Morrison, PG Ince, CJ McDermott, PJ Shaw. Neurogenetics 2010:11:217-225.
Population variation in oxidative stress and astrocyte DNA damage in relation to Alzheimer-type pathology in the ageing brain. JE Simpson. PG Ince, LJ Haynes, R Theaker, C Gelsthorpe, L Bazter, G Forster, GL Lace, PJ Shaw, FE Matthews, GM Savva, C Brayne, SB Wharton on behalf of the MRC Congitive Function and Ageing Neuropathology Study Group. Neuropathol Appl Neurobiol 36:25-40; 2010.
Novel FUS/TLS mutations and pathology in familial and sporadic amyotrophic lateral sclerosis. C Hewitt, J Kirby, JR Highley, JA Hartley, R Hibberd, H Hollinger, TL Williams, PG Ince, CJ McDermott, PJ Shaw. Archives of Neurology 2010;67:1-8.
Astrocyte phenotype in relation to Alzheimer-type pathology in the ageing brain. JE Simpson, PG Ince, G Lace, G Forster, PJ Shaw, F Matthews, G Savva, C Brayne, SB Wharton. Neurobiol Ageing 2010;31:578-590.
Amyotrophic lateral sclerosis and other motor neuron diseases. PJ Shaw. Chapter 418. In Cecil Textbook of Medicine 24th Edition. Editor: Lee Goldman. Elsevier, 2010 (In Press).
Evaluation of two different methods for per-oral gastrostomy tube placement in patients with motor neurone disease (MND): PIG Versus PEG procedures. G Chavada*, A El-Nayal*, F Lee, SJ Webber, M McAlindon, T Walsh, H Hollinger, CJ McDermott,PJ Shaw. Amyotrophic Lateral Sclerosis 2010 (epub June 16).
Common variants at 7p21 associated are 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.
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)
Downregulation of genes with a function in neurite outgrowth and synapse formation in motor neurons of the VEGFδδ mouse model of amyotrophic lateral sclerosis. A Brockington, PR Heath, H Holden, P Kasher, F Bender, M Autiero, F Claes, D Lambrechts, M Sendtner, P Carmeliet, PJ Shaw. BMC Genomics 11: 203; 2010 (e Pub March 26).
An evaluation of neurophysiological criteria used in the diagnosis of motor neurone disease. CP Douglass, RH Kandler, PJ Shaw, CJ McDermott. J Neurol Neurosurg Psychiatry 81:646-649;2010. Accompanying editorial from Professor Kerry Mills.
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 2010 (In Press).
Systemic delivery of scAAV9 expressing SMN 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 Jun 9;2:35ra42.
Validation of the Historical Adult Physical Activity Questionnaire (HAPAQ) against objective measurements of physical activity. H Besson*, C A Harwood", U Ekelund, F M Finucane, CJ McDermott, PJ Shaw*, NJ Wareham*. Authors with equal contribution. International Journal of Behavioral Nutrition and Physical Activity 2010 Jun 24:7:54.
Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome wide association study. A Shatunov, K Mok, S Newhouse, M Weale, B Smith, M Van Es, L Van Den Berg, W Robberecht, O Hardiman, AE Farmer, CM Lewis, A Butler, O Abel, PM Andersen, V Silani, BTraynor, J Melki, JE Landers PhD, P McGuffin, H Pall MD FRCP, N Leigh, J Hardy, RH Brown Jr MD DPhil, JF Powell, R Orrell, K Morrison BMChB DPhil, PJ Shaw, CE Shaw, A Al-Chalabi*. Lancet Neurology 2010 (E pub Aug 27).
