Cardiac Muscle Contraction

The main goal of our laboratory is to understand the molecular mechanisms of cardiac muscle dynamics in normal and diseased states. Particularly our interests focus on the relationships between thin filament activation and crossbridge kinetics, and how the mechanotransduction signaling transmits to myofilament activation. We use multiple techniques, molecular, cellular, biochemistry, structural and biophysical, to obtain information on the fundamental regulatory mechanisms of cardiac muscle contraction. We have demonstrated that exchange of myofibrillar protein can be achieved via a single transgenic manipulation, since stoichiometry of myofibrillar protein is accurately maintained. Using this approach, the mutant contractile proteins are exchanged for endogenous proteins in the mouse heart. Cardiac function is measured by work-performing heart preparations or by echocardiogram, and force/calcium is measured at the myofilament level. We have recently established that using the combined Atomic Force Microscopy (AFM) and fluorescence microscopy technologies, quantitative information on the interaction of mechanical forces with integrins-extracellular matrix protein bonds could be obtained. This has allowed us to study the mechanotransduction mechanisms in cardiomyocytes.

Lymphatic Muscle Contraction

In addition, our laboratory is interested in understanding the regulatory mechanisms of the lymphatic muscle contraction. The lymphatics normally transport fluids and proteins against net hydrostatic pressure and protein gradients. Lymphatic muscle has strong/phasic contractions, much higher shortening velocities and different intracellular calcium dynamics. The lymphatic muscle contractile characteristics indicate that the lymphatic pump acts similar to the heart in its generation of flow. We have shown that lymphatics from different regions of the body exhibited significant functional and contractile differences; in addition lymphatic muscle has a unique combination of smooth and striated muscle components that fit the multi-functional roles of the lymphatic vessels. We investigate the roles of regulatory proteins in lymphatic muscle contraction by using isolated vessel preparations from rat mesenteric and thoracic duct lymphatics along with pharmacological and siRNA approaches. Furthermore we use mouse embryoid body model to address the mechanisms of lymphatic vessel development. Understanding the mechanisms of lymphatic muscle biology is extremely important to ongoing attempts to better understand the lymphatic function and to discover the pathogenesis and the effective treatment of different forms of lymphedema.