0113 206 5274
Summary: Professor of Anaesthesia, Director Leeds Institute of Biomedical And Clinical Sciences, School of Medicine
Location: Clinical Sciences Building, St James’s University
Teaching Commitments: MB ChB years 1 and 4
I attended St Mary’s Hospital Medical School and graduated MB BS (University of London) in 1984. After house jobs in London and Newcastle I commenced GP training in North Yorkshire. As part of this training scheme I did anaesthetics and became hooked.
I undertook my formal research training in Leeds in conjunction with completion of higher specialist training as Lecturer. My supervised MD work centred on tissue bath pharmacological challenge studies of human and rat skeletal muscle. As part of this work I was the first to describe the utility of ryanodine in distinguishing muscle from patients with malignant hyperthermia from normal muscle. Such tests are now used world-wide as a supplementary diagnostic test in MH. I also used in vitro pharmacological challenge tests to identify a pharmacogenetic skeletal muscle abnormality in survivors of exertional heat stroke. While undertaking my MD work I realised the need to acquire a range of additional experimental techniques in order to explore related avenues in MH research. I therefore spent time in colleagues’ laboratories learning basic cellular electrophysiological techniques, patch clamp and fluorescence imaging: this led to fruitful collaborations exploring the mechanisms of action of anaesthetics on neuronal and cardiac cells.
We commenced molecular genetic analysis of UK MH families in 1989 and this has become an increasing focus of my work, especially since 1996 when I took over the lead of our multidisciplinary MH genetics group. Much of our early work involved family studies (linkage and association techniques) of our large well-characterised patient resource but with evolving technology we turned to high-throughput Sanger sequencing to identify novel mutations in RYR1 and CACNA1S. Most recently we have employed Next Generation Sequencing to increase efficiency of variant detection in RYR1 and CACNA1S and, in collaboration with colleagues in University of Washington, Seattle, we have sequenced the exomes of a cohort of MH patients in the search for novel genes associated with MH.
Integral to our understanding of the genetics of MH is functional analysis of genetic variants associated with the condition. We have in-house facilities for functional analysis of novel potentially pathological RYR1 variants using site-directed mutagenesis and homologous & heterologous expression systems. For CACNA1S and other genes functional analysis is done in collaboration with our NIH-funded Program Project Partners.