Drug metabolism, Genetics, Heart, Ion transport, Knockout, Mouse, Pharmacokinetics, Pharmacology, Polymorphism
Abnormalities of cardiac rhythm are a common and serious public health problem. However, the therapies used to treat arrhythmias are often ineffective, and can sometimes even exacerbate arrhythmias. Research in this laboratory is directed at elucidating mechanisms underlying abnormalities of cardiac rhythm and mechanisms underlying variable responses to antiarrhythmic drug treatments. Since antiarrhythmic drugs affect the function of cardiac ion channels, it is one working hypothesis in the laboratory that variable responses to drug therapy may reflect variable function or expression of genes encoding ion channels or proteins involved in drug disposition. Thus, a major focus of work in the laboratory is elucidation of factor(s) that determine ion channel gene expression in cardiac tissue. Approaches include identification of new genes, identification of DNA polymorphisms and characterization of their functional effects on disease and drug responses, and modulation of expression in cultured heart cells (e.g. by antisense) and gene knockout in mice.