Our research group has a strong commitment to research on Amyotrophic Lateral sclerosis (ALS) through molecular genetics, expression profiling in spinal cord and through the use of experimental models to develop new therapeutic approaches. Our major goal has been to identify disease genes associated with the dominantly inherited familial form of ALS (FALS) which, although rare, accounting for 5% of cases, is clinically indistinguishable from the sporadic form of the disease. In order to do this, we have established a resource of ~ 200 families. To date, mutations have been identified in ~70% of these families. The most recently identified mutations causing ALS, frontotemporal dementia (FTD) or ALS/FTD are large hexanucleotide repeat expansions found in a gene of unknown function, C9ORF72), which account for 38% of familial cases of ALS and 6% of sporadic cases in the UK and is characterised by TDP-43-positive ubiquitinated inclusions, the typical hallmark of sporadic cases. Our group has also made key contributions to understanding the role of the small heat shock protein, HSP27 (HSPB1) in the mammalian brain and spinal cord, from the characterisation of the expression of HSPs in stroke and seizures to the demonstration that HSP27 can reduce seizures, attenuate caspase 3 induction and protect against hippocampal cell death. Furthermore, we showed that HSP27 rescues motor neurones and preserves muscle function following injury.
Membership of External Committees.
Member of the Motor Neurone Disease Association Research Advisory Panel (2009-)
International Scientific Committee. Agency for Research on Amyotrophic Lateral Sclerosis (2009-)
Member of the Council of the European Society for Neurochemistry
International Programme Committee for the International Society of Neurochemistry, Busan, South Korea August 2009.
Fellow of the Royal College of Pathologists 1996-
Fellow of the Society of Biology 2011-
et al., NEK1 variants confer susceptibility to amyotrophic lateral sclerosis, Nature Genetics
et al., 2017, Mutations in the vesicular trafficking protein annexin A11 are associated with amyotrophic lateral sclerosis, Science Translational Medicine, Vol:9, ISSN:1946-6234
et al., 2017, Characterisation of the pathogenic effects of the in vivo expression of an ALS-linked mutation in D-amino acid oxidase: Phenotype and loss of spinal cord motor neurons, Plos One, Vol:12, ISSN:1932-6203
et al., 2016, NEK1 variants confer susceptibility to amyotrophic lateral sclerosis, Nature Genetics, Vol:48, ISSN:1061-4036, Pages:1037-+
et al., 2016, CCNF mutations in amyotrophic lateral sclerosis and frontotemporal dementia, Nature Communications, Vol:7, ISSN:2041-1723