University of Pittsburgh

The primary research interest of my lab is in defining the molecular mechanisms involved in the assembly, trafficking, localization and second-messenger-dependent regulation of the intermediate (IK) and small (SK) conductance, Ca²⁺-dependent K⁺ channels. These channels are crucial in a wide array of physiological processes, including endothelial function and hence vascular tone, the regulation of action potential firing frequency, epithelial ion transport, cell growth and differentiation and T-cell activation. We currently have 3 main foci in the lab. First, we are using patch-clamp methodologies in combination with variance analysis, computer modeling and mutagenesis to further define the Ca²⁺-dependent gating processes of these channels. Second, we are using a combination of protein biochemical and fluorescence imaging techniques to study the endocytic trafficking, recycling and ubiquitin-mediated degradation of these channels both in heterologous (HEK cells) and endogenous (human microvascular endothelial cells) expression systems. Finally, we are studying the physiological role of the SK3 homologue in C. elegans using both knockout and transgenic worms as well as expressing the individual splice variants of this channel heterologously to obtain a clearer biophysical fingerprint of these channels.