Professor Dame Pamela J Shaw MBBS MD FRCPPam Shaw

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 22295
Fax: +44 (0)114 22 22292
Email: : pamela.shaw@sheffield.ac.uk

Academic Secretary: Bev Carter
Tel: +44 (0)114 2222295
Email: bev.carter@sheffield.ac.uk

Clinical Secretary: Erica Waines
Email: Erica.Waines@sth.nhs.uk
Tel: +44 (0)114 271 3188

Professor of Neurology, University of Sheffield

Director, Sheffield Institute of Translational Neuroscience (SITraN)

Director, Sheffield Care and Research Centre for Motor Neuron Disorders

Consultant Neurologist, Sheffield Teaching Hospitals NHS Foundation Trust

Associate Director Dementia and Neurodegenerative Diseases Clinical Research Network (DeNDRoN)

Biography

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.

Recent post-graduate awards include: ABN Sir Charles Symonds award (1991;1996;2001); American Academy of Neurology Sheila Essey award 2001; Royal College of Physicians Jean Hunter award 2006 and the International ALS/MND Forbes Norris award 2007.

Research Interests

Professor Shaw’s research is focused on 3 main goals:

To understand the function of motor neurones in health and disease and to translate basic science findings into health benefits for patients with degenerative motor system disorders.

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.

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 she has supervised the research training of 103 individuals from medicine and science including 30 PhD/MD students.

Current Projects

Professor Shaw is a Clinician Scientist in Neurology 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:

  1. Identification of cell specific features of motor neurons which underlie susceptibility to neurodegeneration
  2. Understanding the cellular pathways of motor neurone injury in the presence of mutant SOD1 using a combination of cell biology, proteomics and gene expression profiling
  3. Identifying the different subtypes of motor neuron disease (MND) based on genetics and molecular pathology
  4. Development of new small molecule and gene therapy candidate treatments for patients using stages screening programmes in cellular and other experimental model systems
  5. Promoting the introduction of one neuroprotective drug for MND into clinical practice – riluzole
  6. Establishing the role of non-invasive ventilation (NIV) in improving the quality of life and prolonging survival of MND patients.

Professor Shaw’s research is funded by the Wellcome Trust, the Medical Research Council, NIHR, the Motor Neurone Disease Association, EPSRC, the European Union and biotechnology & pharmaceutical industry partners. Since 1983 she has generated more than £44m in research income.

Awards

  • 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 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
  • 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

Professional Activities

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

• Muscle and Nerve
• Editorial Panel for Research Frontiers in Science, British Medical Journal.
• Editorial board of Amyotrophic lateral sclerosis
• Editorial Board of Brain

She has been a research advisory panel member for the Wellcome Trust, MNDA, MRC and the Muscular Dystrophy Association and reviews for multiple grant awarding bodies.

Membership of National and International Committees

• Member of MRC strategic group for neurodegeneration (from?) 2008.
• Invited expert participant in the NICE panel for the evaluation of riluzole therapy.
• 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.
• External assessor for Parkinson´s Disease Society (from?) 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.
• Member of the European Neurological Society Scientific Committee on MND from 1998.
• Advisor to the Department of Health Medicines Control Agency/ Committee on Safety of Medicines from 1997.
• World Federation of Neurology Working Group on Therapeutic Trials in ALS/MND from 1996.

Previous Activities

• Guarantor of the Brain Trust from 1998-2010.
• Chairman of the ALS/MND International Scientific Programme Committee from 2004 -2010.
• Member of the UK Medical Research Council College of Experts from 2005-2010.
• Member of the Academy of Medical Sciences Fellowship Panel from 2007-2010.
• Wellcome Trust / Academy of Medical Sciences New Lecturer Awards panel from 2009-2010.
• Medical advisor to Oxford Biomedica from 2005-2009.
• Member of the Academy of Medical Sciences Clinical Academic Training Panel from 2008-2009.
• Member of UKCRN Experimental Medicine Committee 2007-2009.
• Member of HEFCE Senior Lectureship awards panel from 2006 -2009.
• UKCRC/ MRC Brain Bank Strategy Advisory Committee 2007 – 2008.
• Member of the Association of British Neurologists Clinical Research and Academic Committee from 1998-2007.
• 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 Muscular Dystrophy Campaign Research Advisory Panel from 2004-2007.
• Member of the scientific panel for the International Congress on Neuromuscular disorders 2004 –2006.
• Member of organising scientific panel for the European Federation of Neurological Societies (EFNS) 2004 -2006
• Member of the Wellcome Trust Neurosciences Panel from October 2001 -2004.
• Member of Meetings Subcommittee of the Association of British Neurologists from 2001-2003.
• Invited external assessor Neuroscience review panels, University of Glasgow and Imperial College London 2003.
• Novartis ALS/MND advisory board 2002.
• Steering committee International MND trial ONO Pharmaceuticals 2002.
• Wellcome Trust / Irish Health Board New Blood Fellowship panel from 1998 to 2000.
• Secretary to the European ALS Study Group from 1997 to 2000.
• Coordinator of the Molecular/ Cell Biology Section of the European Familial ALS Group from 1997 to 2000.
• 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.

Principal Funding Sources

• The Wellcome Trust
• The Motor Neurone Disease Association
• The Medical Research Council
• NIHR
• European Union

Research income since 1983 >£44m.

ResearchTeam

Scientific research team

Channa Hewamadduma
Laura Ferraiuolo
Robin Highley
Emily Goodall
Marc da Costa
Adrian Higginbottom
Richard Mead
Paul Heath
Paul Sharp
Jonathan Cooper-Knock
Scott Allen
James Alix

Clinical Research Team

Chris McDermott
Channa Hewamadduma
Hannah Hollinger
Theresa Walsh
Alison Proctor
Muhammad Rafiq
Susie Crawford
Haris Stavroulakis
Daniel Blackburn
Tom Jenkins

Selected Publications

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).