Sudden cardiac death (SCD) is a leading cause of death in western countries: coronary artery disease is the major cause of SCD in older subjects while inherited arrhythmogenic diseases are the leading cause of SCD in younger individuals. Dr Priori has dedicated her clinical and research activity to the understanding of the molecular mechanisms underpinning inherited arrhythmias and since 2013 she has focused her attention to the development of molecular therapies for these conditions. One of the major challenges in the field is represented by the lack of models for the arrhythmogenic syndromes of interest, therefore part of the research of the team is dedicated to the development of disease models spanning from induced pluripotent stem cells derived myocytes differentiated from tissue of affected individuals to knock in and knock out mice and knock in and knock out pigs.
At present the research of the team is focused on two severe inherited arrhythmogenic diseases: catecholaminergic polymorphic ventricular tachycardia (CPVT) and Long QT syndrome type 8 (LQT8). The group is currently working on two existing mice models for the dominant and the recessive forms of CPVT with the objective of investigating the effects of gene therapy strategies developed by the Molecular Cardiology Laboratories at the ICS Maugeri Institute in Pavia (Italy) on intracellular calcium handling and cellular electrophysiology. A most ambitious effort of the group is the development of a knock-in pig to model LQT8.
The laboratory is currently funded by the ERC advanced grant to Dr Silvia Priori that is targeted to investigate innovative strategies of gene-delivery, gene-silencing and gene-editing to the heart comparing efficacy of different constructs and promoters.
Pivotal to the activity of the team is the collaboration with other research groups at CNIC. The group investigates ultrastructural abnormalities of the key mutant proteins that cause inherited arrhythmias in collaboration with the Microscopy unit lead by Dr. Valeria Caiolfa. Also studied are trascriptomic and proteomic aspects of pivotal proteins involved in calcium handling in CPVT and LQT8, in collaboration with different investigators and unit leaders such as Drs. Enrique Lara, Miguel Torres Sánchez, Jesús Vasquez Cobos and Ana Dopazo.