Our Research

We are broadly interested in understanding atomic-scale mechanisms of how membrane proteins function under normal and diseased states. Membrane proteins play critical roles in nearly every aspect of physiological processes that encompass relaying signals between cells, transporting small molecules and ions across membrane and catalyzing vital enzymatic reactions. Importantly, membrane proteins constitute ~ 60% of targets of currently approved drugs and thus in-depth knowledge about their inner workings is sorely needed to inform the development of effective therapeutic strategies for the treatment of various human diseases.

Our current research program focuses on structures, physiology, pathology, and pharmacology of receptors, transporters, and ion channels that play pivotal roles in the kidneys and, when malfunction, cause various diseases in human. In particular, we are focusing on two classes of membrane proteins: polycystic kidney disease proteins PKD1 and PKD2, and cation-chloride cotransporters (CCCs). PKD1 and PKD2 are the sites of mutations that cause a prevalent and incurable genetic disorder autosomal dominant polycystic kidney disease (ADPKD). Several CCC transporters are the molecular targets of diuretics that are the cornerstone for the treatment of fluid overload and hypertension. Besides elucidating structure-function relationships of polycystic kidney disease proteins and CCCs, we are also interested in developing pharmacological tools mainly for dissecting their functions, but also as drug leads for developing novel therapeutic strategies. To achieve these goals, we employ a multidisciplinary approach that includes molecular biology, protein biochemistry, pharmacology, ion channel electrophysiological, and X-ray crystallography and single-particle electron cryo-microscopy (cryo-EM).