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Professor Christopher E Shaw  MBChB, MD, FRACP, FRCP(hon)
Professor of Neurology and Neurogenetics
Director of the Centre for Neurodegeneration Research
Director of the Maurice Wohl Clinical Neuroscience Institute
Co-Lead for Clinical Neuroscience Clinical Academic Group for King's Health Partners

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tel+44 (0)207 848 5183
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address

Institute of Psychiatry
Box  P041
De Crespigny Park
London
United Kingdom, SE5 8AF

location 105
1 - 2 Windsor Walk
departmentsClinical Neuroscience
Neurodegeneration and Brain Injury
alsoMotor Neurone Disease (MND) / Amyotrophic Lateral Sclerosis (ALS)
RNA Processing Proteins and Neurodegeneration

biography

Christopher Shaw is Professor of Neurology and Neurogenetics at the Institute of Psychiatry, King’s College London. His early training in General Medicine and Neurology was conducted in New Zealand. He came to Cambridge in 1992 on a Wellcome Trust Fellowship to study Neurobiology. In 1995 he moved to the Institute of Psychiatry.

He is Director of the Maurice Wohl Clinical Neuroscience Institute and Director of the Centre for Neurodegeneration Research. He is also Co-Lead for the Clinical Neuroscience Clinical Academic Group for King’s Health Partners.

His major area of clinical and research interest is in the genetic and molecular basis of motor neurone disease (MND, also known as Amyotrophic Lateral Sclerosis or Lou Gherig’s disease). He runs a clinic for patients with MND/ALS at King’s College Hospital.

activities and interests

Head of laboratory researching amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive neurodegenerative disorders that share a common pathogenesis.

His research team are currently hunting new ALS and FTD disease causing gene mutations using genetic linkage, exome capture and next generation sequencing.

Recent findings include the identification of mutations in RNA processing genes TARDBP (Sreedharan et al Science 2008) and FUS (Vance et al Science 2009) confirming that their mis-accumulation plays a pivotal role pathogenic role in the neurodegenerative cascade.

We have generated a range of cellular and animal models of TDP-43 and FUS disease that recapitulate key pathological features in man that influence RNA splicing and neuronal survival (Nishimura et al., Brain 2010; Tollervey et al., Nature Neuroscience 2011; Bilican et al., PNAS 2012).

We were the first group to identify a locus on Chromosome 9p for ALS and FTD (Vance et al., Brain 2006) that was subsequently identified as a massive intronic hexanucleotide repeat expansion mutation in the gene C9ORF72. We have shown that mutant C9ORF72 is the single most common cause of ALS in Europe, arising from a single event around 6,300 years ago (Smith et al EJHG 2012). We also the first to describe the pathological hallmark of mutant C9ORF72 being p62 inclusions in the cerebellum and hippocampus (Al-Sarraj et al., Acta Neuropath 2011) and showed that TDP-43 mislocalisation is essential for neurodegeneration.

We are working with industrial partners to develop cellular models of TDP-43 pathology suitable for drug discovery.

publications

Ten most relevant publications
1. Bilican B, Serio A, Barmada SJ, Nishimura AL, Sullivan GJ, Carrasco M, Phatnani HP, Puddifoot CA, Story D, Fletcher J, Park IH, Friedman BA, Daley GQ, Wyllie DJ, Hardingham GE, Wilmut I, Finkbeiner S, Maniatis T, Shaw CE, Chandran S. Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability. Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5803.

2. Tollervey JR, Curk T, Rogelj B, Briese M, Cereda M, Kayikci M, König J, Hortobágyi T, Nishimura AL, Zupunski V, Patani R, Chandran S, Rot G, Zupan B, Shaw CE, Ule J. Characterising the RNA targets and position-dependent splicing regulation by TDP-43. Nat Neurosci. 2011 Apr;14(4):452-8.

3. Al-Sarraj S, King A, Troakes C, Smith B, Maekawa S, Bodi I, Rogelj B, Al-Chalabi A, Hortobágyi T, Shaw CE. p62 positive, TDP-43 negative, neuronal cytoplasmic and intranuclear inclusions in the cerebellum and hippocampus define the pathology of C9orf72-linked FTLD and MND/ALS Acta Neuropathol. 2011;122:691-702.

4. Tollervey JR, Wang Z, Hortobágyi T, Kayikci M, Joshua T. Witten JT, Zarnack K, Clark TA, Schweitzer AC, Rot G, Curk T, Rogelj B, Briese M, Cereda M, Kayikci M, König J, , Nishimura AL, Zupunski V, Patani R, Chandran S, Rot G, Zupan B, Rogelj B, Shaw CE, Ule J. Analysis of alternative splicing associated with aging and neurodegeneration in the human brain. Genome Research 2011 2011 Oct;21(10):1572-82

5. Vance C, Rogelj B, Hortobagyi T, De Vos KJ, Sreedharan J, Hu X, Wright P, Nishimura AL, Ganeslingam J, Tripathi V, Smith B, Ruddy D, Al-Saraj S, Al-Chalabi A, Leigh PN, Blair IP, Nicholson G, de Belleroche J, Gallo J-M, Miller CC, Shaw CE. Mutations in FUS, an RNA processing protein, cause familial ALS type 6 Science 2009;323:1208-11.

6. Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogelj B, Ackerley S, Durnall JC, Williams KL, Buratti E, Baralle F, de Belleroche J, Mitchell JD, Leigh PN, Al-Chalabi A, Miller CC, Nicholson G, Shaw CE. TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis. Science 2008;319:1668-72.

7. King A, Al-Sarraj S, Shaw CE. Frontotemporal Lobar degeneration with ubiquitinated tau-negative inclusions and additional a-synuclein pathology but also unusual cerebellar ubiquitinated p62-poitive, TDP-43 negative inclusions Neuropathology 2008, 29:466-71.

8. Vance C, Al-Chalabi A, Smith BN, Hu X, Sreedharan J, Siddique T, Schelhaas HJ, Kusters B, Troost D, Baas F, De Jong V, Shaw CE.. Familial amyotrophic lateral sclerosis with frontotemporal dementia is linked to a locus on Chromosome 9p13.2. Brain 2006 129:868-76.

9. Broom WJ,. Parton MJ, Vance CA, Russ C, Andersen PM, Hansen V, Leigh PN, Powell JF, Al-Chalabi A, Shaw CE. No association of the SOD1 locus and disease susceptibility or phenotype in sporadic ALS. Neurology 2004, 63:2419-22.

10. Ruddy DM, Parton MJ, Al-Chalabi A, Lewis C, Leigh PN, Powell JF, Siddique T, Postumus Meyjes E, Frank Baas, De Jong V, Shaw CE.. Two families with familial amyotrophic lateral sclerosis are linked to a novel locus on Chromosome 16q. American Journal of Human Genetics 2003; 73 360-369.

last updated: Monday, May 28, 2012