The major thrust of our research is amyotrophic lateral sclerosis (ALS), also known as Motor Neurone Disease. ALS is the most common adult onset neuromuscular disease. It is a highly debilitating condition and there are currently no effective treatments. We have used multiple approaches to study ALS starting with gene identification in familial cases, which make up 10% of ALS cases, and in parallel we have used gene expression, cell culture and experimental models to elucidate mechanisms and explore potential targets for treatment.
We have recruited a cohort of over 208 kindred, that have contributed to the identification and characterisation of novel mutations in TARDBP, FUS, VAPB, DAO, sequestosome and the chromosome 9 locus (C9ORF72) harbouring the most prevalent cause of FALS and certain forms of frontotemporal dementia.
We have also carried out functional studies using spinal cord tissue, cell culture and experimental models which have yielded valuable information about the pathways affected by FALS mutations and common to sporadic cases, which extend from defects occurring in protein trafficking from the nucleus to the cytoplasm, from the ER to Golgi and protein degradation via proteasomal and lysosomal pathways. Specific examples are VAPB mutations that impair the IRE1 component of the UPR, a modifier action of PDI, another ER protein, affecting survival and mutations in DAO, a peroxisomal enzyme, that recaptitulate disease in motor neurons.
I am actively involved in teaching undergraduate and postgraduate students in the medical course and am Director of the Neuroscience and Mental Health BSc course and have supervised 20 PhD students, one MD project and two external London University PhD students to completion.