Dr. Dudley’s lab is interested biophysical approaches to cardiovascular disease. The lab spans basic science to clinical trials approaches. Specific projects include determination of the structural biology of ion channels, evaluating the molecular basis of arrhythmia linked to human gene defects, the use of electrochemical and electron spin resonance methods to measure nitric oxide and superoxide in real time, and the use of stem cells, native or genetically engineered, as replacement tissue and producers of endocrine factors.

Currently, the lab is developing a molecular model of voltage-gated sodium channel outer vestibule, selectivity filter, and antiarrhythmic drug binding site as a prelude to rational drug design efforts. In the absence of direct structural data, we have been able to constrain possible models by determining specific points of contact between the channel and high affinity ligands of known structure using thermodynamic mutant cycle analysis.

Also, we are using a variety of stem cell models to study arrhythmogenesis and cardiac cell transplantation. We are investigation the directed differentiation of stem cells, their proliferative potential, and the mechanism whereby these cells improve myocardial function after a heart attach. We are using transgenic technology to develop in vitro models of the inherited arrhythmias, Long QT Syndrome and Idiopathic Ventricular Tachycardia. We are investigating whether myocytes derived from embryonic stem cells will cause arrhythmias when used in cell transplantation.

Using electrochemical and spin trap techniques, the lab can measure nitric oxide (NO) and reactive oxygen species (ROS) release from a small number of cells. Currently, the lab is evaluating the hypotheses that ROS and NO are differentially regulated during the development of atrial fibrillation and that endocardial NO may play a role in regulating myocardial function.