Our laboratory focuses on structure-function relationships in the regulation of calcium transport in the heart. We study the molecular structure of the Ca²⁺-ATPases from the endoplasmic reticulum (ER) and sarcoplasmic reticulum (SR) with the overall aim of revealing the molecular basis of calcium transport and mechanisms of regulation. These Ca²⁺-ATPases pump calcium from the cytosol at the expense of ATP, thereby lowering cellular calcium concentrations and triggering a variety of physiological responses including heart muscle relaxation. Defects in these calcium transport mechanisms have been implicated in heart disease (hypertrophy, cardiomyopathy, hypertension, end-stage heart failure).

To achieve these goals, we utilize electron cryomicroscopy, x-ray crystallography and biochemical techniques to study the structure and function of Ca²⁺-ATPases. The primary focus of our laboratory is the molecular basis for the regulation of heart muscle relaxation by phospholamban and sarcolipin. For these studies, we use a combination of biochemistry and electron and x-ray crystallography to obtain three-dimensional structural information. Two examples of our recent studies include (1) Electron crystallographic analyses examining the interaction between Ca²⁺-ATPase, phospholamban and sarcolipin in two-dimensional crystals; and (2) X-ray crystallographic analysis of the inhibitory complex of a mycotoxin bound to Ca²⁺-ATPase.