Christopher Shaw

Professor of Neurology and Neurogenetics

King’s College London, UK



Christopher Shaw is Professor of Neurology and Neurogenetics at the Institute of Psychiatry, Psychology and Neuroscience, King’s College London. He is Head of the Department of Basic and Clinical Neuroscience and Director of the Maurice Wohl Clinical Neurosciences Institute leading a faculty of 35 and 170 staff and PhD students. He also works as a Consultant Neurologist at King’s College Hospital where he runs a clinic for people with motor neuron disorders. His early clinical training in General Medicine and Neurology was conducted in New Zealand. He came to Cambridge, UK in 1992 on a Wellcome Trust Fellowship to study Neurobiology. After 3 years studying the molecular signalling between neurons and oligodendroglia he moved the Institute of Psychiatry in 1995. Over the past 20 years his team have created one of the world’s largest Biobanks of DNA samples, lymphoblast cell lines and post mortem tissues from patients with ALS. This has underpinned his research exploring the genetics, molecular and cellular pathobiology of ALS. His contributions to the field include the identification of many novel SOD1 mutations and description of the associated molecular pathology. His team were the first to identify mutations in TARDBP, which encodes TDP-43 in familial and sporadic ALS and demonstrate their neurotoxicity. They have subsequently identified the proteins that regulate TDP-43 nucleo-cytoplasmic shuttling, identified the major RNA binding targets and the pathways regulating its proteostasis. They have generated mutant TDP-43 transgenic mouse and patient induced pluripotent stem cells IPS-derived neurons and glia from TDP-43 mutant patients recapitulate key features of human ALS pathology. Using genome-wide linkage they identified a novel locus for familial ALS on chromosome 16q and subsequently identified mutations (FUS) in ~3% of all familial cases. They were the first to demonstrate that FUS mutations disrupt the nuclear localising signal leading to cytoplasmic aggregates. They subsequently generated a transgenic mouse model with FUS overexpression leading to an ALS phenotype. They were the first to demonstrate linkage to Chromosome 9p in an ALS and frontotemporal dementia (FTD) kindred subsequently shown by others to be an expanded G4C2 hexanucleotide repeat and the most common mutation for ALS and FTD. Subsequently they demonstrated the hallmark cerebellar pathology (Al-Sarraj 2011) and that specific RNA binding proteins are sequestered in RNA foci. Their exome sequencing effort in familial ALS is on-going with a recent discovery of mutations in TUBA4A and Annexin 11 and several other unpublished candidates undergoing functional studies.