Dr Arash Yavari BSc, MBBS, MRCP

Wellcome Research Training Fellow

Research summary

My research investigates a novel AMP-activated protein kinase-dependent model of hypertrophic cardiomyopathy (HCM) in the Watkins’ group. This project fits in more broadly with the group’s research interests in: i) the identification and characterisation of novel causative pathways underpinning the manifestations of inherited cardiomyopathies; ii) the study of cardiac energetics and metabolism in left ventricular hypertrophy (LVH) and heart failure.
AMPK is a highly-conserved serine/threonine kinase that acts as a cellular energy sensor and a regulator of metabolism in most cell types including cardiomyocytes. Interest in its cardiac role was partly initiated by our and others identification of mutations in the γ2 regulatory subunit (encoded by the PRKAG2 gene) in families with HCM. PRKAG2 mutations are characterized by left ventricular hypertrophy, myocardial glycogen accumulation, electrical pre-excitation through atrioventricular accessory pathways and progressive cardiac conduction system disease. The identification of mutations in a non-sarcomeric protein fundamental to cellular energy regulation is consonant with a body of evidence identifying energy deficiency as a major contributor to the phenotype of the cardiomyopathies. Understanding the molecular mechanisms through which PRKAG2 mutations cause their clinical effects is likely therefore to be of importance, both broadly to other inherited and acquired forms of LVH characterised by energy deficient signalling, as well as to patients with AMPK disease.

Research Area

Pathophysiology and cardiac energetics of PRKAG2 cardiomyopathy

Keywords

Cardiac muscle biology; hypertrophic cardiomyopathy; energetics; AMPK; PRKAG2 gene

Contact Details

Department of Cardiovascular Medicine,
University of Oxford
Email arash.yavari@cardiov.ox.ac.uk

Sponsor(s)

Wellcome Trust
British Heart Foundation