The overall research interests of our laboratory are pulmonary vascular physiology and pathophysiology, ion channel electrophysiology, and pathogenic mechanisms of pulmonary vascular disease. We are currently investigating a) the Ca2+ signaling and excitation-contraction coupling in vascular smooth muscle cells, b) the transcriptional and functional regulation of ion channels (K+, Ca2+ and Cl- channels) in pulmonary vascular smooth muscle and endothelial cells, c) the cellular and molecular
mechanisms of hypoxic pulmonary vasoconstriction, d) the pathogenic and therapeutic mechanisms of idiopathic and thromboembolic pulmonary hypertension, and e) the functional role of ion channels in stem cell proliferation and differentiation. Using the combined techniques of patch clamp, digital imaging fluorescence microscopy, cellular and molecular biology, and genetics/genomics, we hope to gain a greater understanding of i) the roles of ion channels and intracellular Ca2+ in the regulation of pulmonary vascular smooth muscle cell proliferation, migration and apoptosis, and ii) how dysfunctional voltage-gated K+ (Kv) channels and upregulated transient receptor potential (TRP) channels in pulmonary arterial smooth muscle cells (PASMC) contribute to the development of pulmonary arterial hypertension.
The research techniques commonly utilized in our lab include: a) recording of whole-cell and single-cell ionic currents using the patch clamp technique; b) measurement of intracellular Ca2+ concentration using digital imaging fluorescence microscopy; c) determination of pulmonary vascular reactivity using isolated perfused/ventilated lung and isolated pulmonary arteries of mouse; d) in vivo measurement of cardiac function and hemodynamics via right heart and pulmonary arterial catheterization in small animals (rats and mice); e) quantification of mRNA and protein expression using real-time RT-PCR, Western blot, and immunocytochemistry; and f) SNP discovery and analysis using blood/DNA samples from patients with pulmonary vascular diseases.