Graduate student, Year 4
Department of Biochemistry and Molecular Biology
Center for Lung Biology
Dr. Donna Cioffi
Department of Biochemistry and Molecular Biology and Center for Lung Biology
I am working to find out the critical role of S100 proteins in the store-operated calcium channel-mediated endothelial dysfunction. The goal of my project is to know how we can protect the endothelial barrier from damage due to entering of calcium into the cells. Endothelial cells line the blood vessels and form a protective barrier in our body. Calcium enters endothelial cells through ion channels. Specifically, entering of calcium through the store-operated calcium ion channel ISOC, causes endothelial cell damage and disruption of the endothelial barrier. This produces leaky blood vessels. Our lab has determined that two proteins FKBP51 and PP5C prevent the entering of calcium into the endothelial cells by blocking the ISOC channel and protect the endothelial barrier, but we do not know how this can happen. My aim is to determine whether calcium dependent S100 proteins play an important role in the FKBP51-PP5C-mediated inhibition of ISOC channel and protection of endothelial barrier. S100 proteins are potent activator of PP5C. Thus, S100 proteins may activate PP5C in the endothelial cells to promote FKBP51-PP5C-mediated inhibition of ISOC channel. My project will be able to identify a critical part of the mechanism which prevents/reverses endothelial barrier disruption and could be targeted to modulate vascular inflammation-associated endothelial dysfunction.
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