Institute of Cardiometabolism and Nutrition, INSERM, France
Inserm researcher since 1980, research director since 1995, I headed the research unit 582 “Pathophysiology and therapy of striated muscle” (2003- 2008), and made a major contribution to the understanding of the genetics of congenital myopathies and muscle dystrophies (1994-2010). My past and current research projects also focused on genetics of hereditary cardiac arrhythmias (long QT syndrome, Brugada syndrome, catecholergic polymorphic ventricular tachycardia, idiopathic ventricular fibrillation, lone atrial fibrillation and early repolarization syndrome) and functional consequences of mutations in ionic channel subunits or associated proteins. We use molecular, immunohistochemical and electrophysiological techniques to determine how mutations that are linked to arrhythmia can alter the function of voltage-gated channels expressed in the heart. We identified numerous mutations in several ionic genes that regulate the repolarization phase of the cardiac action potential, including the voltage-gated K+ channels, and the first KCNQ1 mutations causing Jervell and Lange Nielsen syndrome, a syndrome associating long QT syndrome and deafness, and the cardiac sodium channel. We also studied rare variants in CACNA1C, RYR2 and CALM3 leading to calcium dysregulation identified by exome sequencing. We are interested in SNPs that modify the effect of a lone mutation or explain pleiotropic effect or variable penetrance in families.