Colleges
DPHIL OPPORTUNITIES AVAILABLE
Hugh Watkins
FRS FMedSci
Radcliffe Professor of Medicine
- British Heart Foundation Professor of Cardiovascular Medicine
- Honorary Consultant in Cardiology and General Medicine
- Principal Investigator of CureHeart
- 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.
Key publications
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Association analyses based on false discovery rate implicate new loci for coronary artery disease.
Journal article
Nelson CP. et al, (2017), Nat Genet
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Chronic Activation of γ2 AMPK Induces Obesity and Reduces β Cell Function
Journal article
Yavari A. et al, (2016), Cell Metabolism
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Reassessment Of Mendelian Gene Pathogenicity Using 7,855 Cardiomyopathy Cases And 60,706 Reference Samples
Journal article
Thomson K. et al, (2016), Genetics in Medicine
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A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.
Journal article
Nikpay M. et al, (2015), Nat Genet, 47, 1121 - 1130
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Combination of Whole Genome Sequencing, Linkage and Functional Studies Implicates a Missense Mutation in Titin as a Cause of Autosomal Dominant Cardiomyopathy with Features of Left Ventricular Non-Compaction.
Journal article
Gehmlich K., (2016), Circulation: Cardiovascular Genetics
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Fumarate is cardioprotective via activation of the Nrf2 antioxidant pathway.
Journal article
Ashrafian H. et al, (2012), Cell Metab, 15, 361 - 371
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Metabolic modulator perhexiline corrects energy deficiency and improves exercise capacity in symptomatic hypertrophic cardiomyopathy.
Journal article
Abozguia K. et al, (2010), Circulation, 122, 1562 - 1569
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Genetic variants associated with Lp(a) lipoprotein level and coronary disease.
Journal article
Clarke R. et al, (2009), N Engl J Med, 361, 2518 - 2528
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
Journal article
Speliotes EK. et al, (2010), Nature Genetics, 42, 937 - 948
Recent publications
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Comparing the effects of chemical Ca2+ dyes and R-GECO on contractility and Ca2+ transients in adult and human iPSC cardiomyocytes.
Journal article
Robinson P. et al, (2023), J Mol Cell Cardiol
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Novel insights into diminished cardiac reserve in non-obstructive hypertrophic cardiomyopathy from four-dimensional flow cardiac magnetic resonance component analysis.
Journal article
Ashkir Z. et al, (2023), Eur Heart J Cardiovasc Imaging
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Genetic Determinants of the Interventricular Septum Are Linked to Ventricular Septal Defects and Hypertrophic Cardiomyopathy
Journal article
Yu M. et al, (2023), Circulation: Genomic and Precision Medicine
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Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease.
Journal article
Young WJ. et al, (2023), Nature communications, 14
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Insights into the Role of a Cardiomyopathy-Causing Genetic Variant in ACTN2
Journal article
Broadway-Stringer S. et al, (2023), Cells