Ph.D. University of South Alabama 2006
Calcium signaling and autoantibodies in pulmonary endothelial barrier disruption.
Our group is interested in endothelial dysfunction in the cardiovascular system. We currently have two major focus areas. The first area is in calcium signaling in pulmonary artery and microvascular endothelial cells as it relates to the formation of inter-endothelial cell gaps and disruption of the endothelial barrier in inflammatory processes. Inflammatory mediators promote endothelial barrier disruption by allowing calcium entry across the plasma membrane through store-operated calcium (SOC) entry channels. Within this focus area we are studying regulation of SOC entry channel activation and inactivation. In one project, we are studying how binding of members of the FKBP family of immunophilins regulates SOC entry activation. In this project we will determine whether glucocorticoid upregulation of FKBP51 inhibits activation of SOC entry which may represent a novel anti-inflammatory mechanism of glucocorticoids.
Another project in the calcium signaling focus area studies the mechanism(s) underlying inactivation of one particular SOC entry channel, the ISOC channel. While it is known that ISOC inactivation is both calcium and phosphorylation dependent, it is not known whether the phosphorylation and calcium mediated pathways are part of a common mechanism. In this project, we are seeking to address the hypothesis that endothelial ISOC inactivation is dependent upon phosphorylation and calcium complexation in the proline-rich region of the ISOC channel subunit TRPC4, and is a critical determinant of the magnitude and duration of inter-endothelial cell gap formation.
The second focus area in our group is that of autoantibodies and endothelial cell dysfunction. It is known that people with some underlying autoimmune diseases are predisposed to developing pulmonary hypertension. Endothelial dysfunction, described as "disordered proliferation and angiogenisis", may play a prominent role in the development and progression of severe pulmonary hypertension. We are interested in determining whether autoantibodies contribute to endothelial dysfunction leading to the development of pulmonary hypertension.
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