Investigators and Program Directors

Research Interests

My laboratory's focus is on the structure and function of a calcium ion channel in cardiac muscle. Calcium ions are second messengers in signaling pathways in all types of cells. In the heart, they regulate cardiac muscle contraction, electrical signals that determine the cardiac rhythm, and cell growth pathways. One of the major calcium channels responsible for calcium release from intracellular stores is the ryanodine receptor. The ryanodine receptor plays a crucial role in muscle excitation-contraction coupling, a process in which neuron-induced depolarization of the plasma membrane causes ryanodine receptor molecules to release Ca2+ from the sarcoplasmic reticulum; the resulting increase in cytoplasmic [Ca2+] activates the myofilaments so as to generate muscle contraction. Abnormal calcium release through a dysfunctional cardiac muscle ryanodine receptor has been implicated in a certain type of sudden cardiac death and heart failure.

High resolution cryo-electron microscopy and computational image processing, in conjunction with confocal laser scanning microscopy and fluorescence resonance energy transfer techniques, are being used to determine the three-dimensional structure of ryanodine receptors, and to characterize their conformation dynamics. We are particularly interested in the defective interactions between ryanodine receptor's structural domains and between the receptor and its modulators that physiologically regulate channel functions, and in the abnormal conformational changes that underlie dysfunction of ryanodine receptors. The information will help us to understand the role of ryanodine receptors in excitation-contraction coupling mechanisms, and how the dysfunction of ryanodine receptors leads to cardiac muscle diseases, which in turn may allow rational design of novel therapeutic strategies.

Contact Information

Phone: 518-474-6516
Fax: 518-474-7992
E-mail:liuz@wadsworth.org