Research Interests

Signaling pathways activating TRPC channels and functional role of TRPC in the regulation of endothelial barrier function.

Endothelial cells (EC) form a unique signal-transducing surface in the vascular system. The abundance of ion channels in the plasma membrane of these non-excitable cells has very important functional role in mediating Ca2+ influx and vascular homeostasis. The mammalian homologues of the Drosophila transient receptor potential (TRPC) channel have emerged as primary candidates for Ca2+ entry channels. The level of TRPC1 and TRPC6 mRNA expression is remarkably high in human endothelial cells as compared with the other TRPC subtypes. These high levels raise the interesting question as how these two different members of TRPC family regulate the specific ([Ca2+]i) signaling pathways. My research focuses on how the activation of thrombin receptor on the endothelium regulate the specific ([Ca2+]i) signaling pathways through TRPC channels and the subsequent cascade of events that mediate the loss of endothelial barrier function.

We have shown that thrombin activates the store operated channel (SOC) TRPC1 via PKC{alpha} pathway. The entry of Ca2+ in endothelial cells could also be regulated by the activation of TRPC6, which is a Receptor Activated Cationic Channel (RACC). So, my focus is to address the basis by which thrombin-initiated signals via PAR-1 interaction with Gq regulate both the Store-Operated Channel (SOC) TRPC1 and Receptor Activated Cationic Channel (RACC) TRPC6 channel. And secondly, how each of these 2 distinct TRPC channels contribute in regulating ([Ca2+]i) homeostasis and endothelial permeability.