I am currently Professor of Neurology and Neurogenetics at the Institute of Psychiatry, Psychology and Neuroscience, King’s College London, as well as Head of the Department of Basic and Clinical Neuroscience and Director of the Maurice Wohl Clinical Neurosciences Institute.
I work as a consultant Neurologist at King’s College Hospital where I run a clinic for people with motor neuron disorders.
My early clinical training in General Medicine and Neurology was conducted in New Zealand. I came to Cambridge, UK in 1992 on a Wellcome Trust Fellowship to study Neurobiology. After 3 years in the laboratory of Professor Alastair Compston studying the molecular signalling between neurons and oligodendroglia I moved in 1995 to join Professor Nigel Leigh at the Institute of Psychiatry.
MBChB, MD, FRACP, FRCP (Hon), FMedSci, FANA
Over the past 20 years my team have collected one of the world’s largest biobanks of DNA samples, lymphoblast cell lines and post mortem tissues from patients with amyotrophic lateral sclerosis (ALS). This has underpinned my research exploring the genetics, molecular and cellular pathobiology of ALS. We have described many novel SOD1 mutations, the molecular pathology of ALS, and demonstrate that many mutations did not alter the activity of dismutase (an antioxidant enzyme), but have multiple toxic effects in a range of cellular models.
We were the first to identify specific mutations in familial and sporadic ALS and demonstrate their neurotoxicity, and have subsequently identified many of the proteins involved in the disease’s genesis and progression. Using genome-wide linkage we identified a novel locus for familial ALS on chromosome 16q and subsequently identified mutations (FUS) in approximately 3% of all familial cases. We were the first to demonstrate that FUS mutations disrupt the nuclear localising signal leading to cytoplasmic aggregates, and subsequently generated a transgenic mouse model with FUS overexpression leading to an ALS phenotype.
Our exome sequencing effort in familial ALS is ongoing, and we have recently discovered several more proteins and pathways involved in ALS.