Team 1 – Genomics and Pathophysiology of Cardiovascular Diseases

Team headed by P. Charron

Team 1 focuses its research program on – identification of new genes and genetic variants associated to the susceptibility to rare or frequent cardiovascular diseases, – characterization of their functional roles at the molecular and cellular levels, – finding new pathophysiological mechanisms, in the ultimate goal of a better therapeutic management of patients. This research is built on the use of genetic and transcriptomic techniques (“Micro-array” and “Next-Generation-Sequencing”) and on functional studies of identified genes/variants. The main studied diseases are cardiomyopathies, arrhythmias, coronary artery disease and venous thrombosis.

This team is linked to both “écoles doctorales” 515 “Complexité du Vivant” and 393 “Santé Publique: Epidémiologie & Sciences de l’Information Biomédicale”.

 

Principal investigators’ groups:

  • In Team 1, Pascale Guicheney and Nathalie Neyroud focus their research on genetics of hereditary cardiac arrhythmias (Brugada syndrome, long QT syndrome, short QT syndrome, and ventricular fibrillation) and functional consequences of new mutations in ion-channel subunits and associated proteins with the aim of increasing our understanding of regulatory processes of ion channels involved in human cardiac pathophysiology. They use next-generation DNA sequencing (NGS), molecular, immunohistochemical and electrophysiological techniques, associated to viral gene transfer and animal models to identify new genetic variants and to determine how variants linked to arrhythmia can alter the expression and function of cardiac voltage-gated channels. 
  • One of team 1 research axes aims at unravelling the predictive factors of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). Vasospam, thickening and prolonged contraction of intracranial arteries, is a severe complication of aSAH occurring 4 to 12 days after the bleeding for 15 to 20% of aSAH cases and leading to delayed cerebral ischemia (DCI) responsible for severe neurological deficiencies. To date, there is no predictive factor of vasospasm onset thus every aSAH patient is submitted to a heavy treatment not free of side effects. The discovery of cerebral vasospam predictive factors would thus improve patients nursing at their arrival in neuro-intensive care units. The used approaches to unravel these predictive factors combine transcriptomic, miRNOmic and genetic approaches. This project is led by Sophie Garnier and David-Alexandre Trégouët in close collaboration with Pr. Vincent Degos of Pitié-Salpêtrière neuro-intensive care unit.