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.
Author Correction: Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes (Nature Communications, (2020), 11, 1, (2539), 10.1038/s41467-019-12438-5)
Wang Q. et al, (2021), Nature Communications, 12
Bi-allelic MCM10 variants associated with immune dysfunction and cardiomyopathy cause telomere shortening.
Baxley RM. et al, (2021), Nat Commun, 12
Rationale and design of the African Cardiomyopathy and Myocarditis Registry Program: The IMHOTEP study.
Kraus SM. et al, (2021), Int J Cardiol
Publisher Correction: Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.
Lagou V. et al, (2021), Nat Commun, 12
Functional analysis of a gene-edited mouse to gain insights into the disease mechanisms of a titin missense variant
JIANG H. et al, (2021), Basic Research in Cardiology