Identification of genetic determinants and modifiers of cardiac arrhythmias and sudden cardiac death.

Dr. Lodder focuses on deciphering the genetic and molecular basis of cardiac arrhythmias and cardiomyopathy. Her work covers the entire spectrum from gene discovery in Mendelian disease, to population genetics, systems genetics (including the underlying bioinformatics), and the functional analysis of the genes and pathways identified by these studies in vitro and in vivo. This work reflects her interest in solving cardiovascular problems by working on different integration levels: combining genetics and functional molecular and cellular studies with investigations at the level of the whole organ, organism and population.

One of the main projects, funded by a VIDI grant from the Dutch Research Council: NWO Talent Scheme, focuses on the roles of TNNI3K in cardiac disease. TNNI3K is a pleiotropic kinase, almost uniquely expressed in the heart. Genetic variation in this kinase is associated with cardiac conduction disease, supraventricular arrhythmias, cardiomyopathy and sudden cardiac death in human. In mice higher expression levels are associated with slower conduction, and worsening of cardiac disease such as cardiomyopathy and ischemia reperfusion injury. This project focuses on identification of the downstream targets of TNNI3K and unravelling the molecular pathways underlying the effect of TNNI3K on cardiac (electro)physiology.