Second, we are investigating the use of stem cells for cell transplantation therapy in congestive heart failure. Recently, pluripotent cells have shown the ability to engraft in areas of myocardial damage and to improve cardiac function. These observations suggest the possibility of cardiac cell transplantation as a treatment for cardiomyopathy. In a recent manuscript, we showed that these cells might contribute to arrhythmias, however. We are investigating the influence of injury on electrophysiological differentiation and whether genetically altered stem cells or bone-marrow derived vascular precursor cells can reduce arrhythmic risk. Also, we are comparing cell therapy and tissue engineered approaches to cardiac repair. These projects involve stem cell differentiation, gene targeting, cell culture, FACS sorting, animal models of infarct, histology, and electrophysiology.

Finally, ion channels are responsible for cardiac excitability, but mutations or alterations in transcriptional or translational regulation of ion channels can lead to sudden death. We are identifying families with inherited sudden death syndromes and studying why these mutations/polymorphisms cause the arrhythmia. Also, we are studying ion channel transcriptional regulation by such things as oxidative stress. These experiments involve genetics, molecular biology, expression of ion channels in heterologous systems, electrophysiology to study the effect of mutations on channel behavior, computer modeling to understand the results, and gene targeting to make animal models.