Tiruppathi Lab Research
We are interested in understanding the mechanism(s) that control transport of albumin across the endothelial cell membrane. This transport process is important because
albumin maintains the vascular integrity and also involved in the transport of many physiological ligands into the cell. We have purified a 60 kDa protein (gp60) from endothelial cell
membrane that can bind albumin. Using antibodies raised against gp60, we cross-linked gp60 on the endothelial cells to activate gp60 which increased transport of albumin and other fluid
phase macromolecules in endothelial cells. Moreover, gp60 is associated with caveolin, a main structural component of caveolae. We are investigating the role of gp60 in caveolae-mediated
solute transport in vascular endothelial cells. Further, we are in the process of cloning gp60 to understand the physiological function of gp60 in vascular endothelial cells.
Another area of research interest is the molecular mechanism that regulates vascular inflammation. Proinflammatory mediators, such as thrombin, induce vascular
inflammation by activating specific receptors on the endothelial cell surface. Thrombin binds to and activates a seven transmembrane domain G protein-coupled receptor by cleaving
the receptor in the amino-terminal region. This activation causes cell retraction or cell rounding which increases the paracellular transport of macromolecules. The increased
macromolecules transport across the endothelial barrier leads to vascular tissue inflammation. Currently, we are investigating the signaling pathways in endothelial cells that
are activated by thrombin receptor as well as the regulation of the receptor expression in endothelial cells.