Radcliffe Professor of Medicine and Head of Department
- British Heart Foundation Professor of Cardiovascular Medicine
- Honorary Consultant in Cardiology and General Medicine
- Director of the BHF Centre for Research Excellence
Molecular Genetics and Molecular Biology of the Heart Muscle Disease/Molecular Genetics of Complex Cardiovascular Phenotypes
My interest is in using molecular genetic analysis of cardiovascular disease as a tool to define disease mechanisms and therapeutic targets. I have had a longstanding focus on inherited heart muscle diseases, in particular hypertrophic cardiomyopathy, which is a relatively common Mendelian condition which puts affected individuals at risk of sudden cardiac death. My group's work, using molecular biological, model organism and clinical research approaches, has lead to the idea that energy compromise is a key disease mechanism; clinical trials are underway to test new medical therapies based on this finding. Our work on genetic causes of ‘sudden cardiac death’ syndromes has been translated into clinical practice through the Oxford BRC, leading to an NHS commissioned national DNA diagnostic service. This area of my work is integrally linked with the groups of Dr. Charles Redwood and Dr. Houman Ashrafian as we have worked closely together for many years.
I also lead a research group investigating susceptibility genes for coronary artery disease, now the main cause of premature mortality worldwide. With colleagues in Oxford (Profs Farrall and Collins) and in Europe (Prof Hamsten, Karolinska) I established the Procardis study to assemble the large scale clinical collections needed to tackle this challenge; I have since chaired a large international collaboration in this area (the C4D Consortium). Recent findings include evidence that lipoprotein Lp(a) levels are causally related to coronary disease risk and identification of multiple novel common susceptibility variants for coronary artery disease risk. This work is now entering an exciting phase where we can use functional genomic tools to understand new biology, thus drawing on some of the approaches we have developed in our Mendelian genetic work.
Heritability of haemodynamics in the ascending aorta.
McGurk KA. et al, (2020), Sci Rep, 10
Heterozygous ATP-binding Cassette Transporter G5 Gene Deficiency and Risk of Coronary Artery Disease.
Nomura A. et al, (2020), Circ Genom Precis Med
Genetic Predisposition to Coronary Artery Disease in Type 2 diabetes
van Zuydam NR. et al, (2020), Circulation: Genomic and Precision Medicine
Data-driven modelling of mutational hotspots and in silico predictors in hypertrophic cardiomyopathy.
Waring A. et al, (2020), J Med Genet
Publisher Correction: Whole-genome sequencing of a sporadic primary immunodeficiency cohort.
Thaventhiran JED. et al, (2020), Nature