Ion channels, Ca2+ signaling system, Cardiac muscle cell signaling
Quantitative modeling of complex biological systems
The rhythm and the strength of heart beats are controlled by three dynamic systems in cardiac cells: (1) the electrical system, (2) the Ca2+ signaling system, and (3) the contractile system. In a cardiac cycle, the electric excitation of cardiac muscle cell triggers an increase of the cytosolic Ca2+ concentration, which causes the muscle to contract; the Ca2+ is then sequestered or removed from the cytosol, and the muscle relaxes. My research is to understand the molecular and cellular mechanisms that control these dynamic systems and hence govern the cardiac function in health and disease. We are currently funded by a NIH-R01 grant to study the link between the contractile dysfunction to the electrical arrhythmias in the Familial Hypertrophic Cardiomyopathy.
My current work focuses on the hypertension-induced heart diseases. High blood pressure is a major risk factor for cardiac hypertrophy, arrhythmias and heart failure. So far, the main treatment strategy is to use anti-hypertensive drugs to lower the blood pressure. However, 30-33% of the treated patients still have blood pressure higher than the recommended level of 140/90 mmHg. Hence finding new effective treatment for hypertension-induced heart diseases is of great clinical importance. Recently, we found that the onset of hypertension is associated with an increase of the activity of an important signaling molecule in the heart, the Ca2+-calmodulin-dependent kinase II (CaMKII). Previous studies show that CaMKII plays a key role in modulating cardiac function and regulating heart disease development. My NIH funded project is to investigate the potential of using CaMKII inhibitor as a new therapeutic strategy for treating hypertension-induced heart diseases.
We use multidisciplinary approach to study the complex behavior of the dynamic systems that control cardiac function. Our unique strength comes from closely combining experimental study with quantitative modeling. The major techniques we use include electrophysiology, confocal microscopy, Ca2+ measurement using fluorescence indicators, biochemistry and molecular biology methods, and large scale computer simulations.