Sydney White
Predoctoral trainee (Mehta Lab)
Department of Pharmacology & Regenerative Medicine
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About
Advisor: Dolly Mehta
Co-mentor: Kostandin Pajcini
Title: Understanding Endothelial Plasticity and Signaling in Lung Injury
Abstract: Endothelial plasticity is a critical determinant of vascular repair and remodeling during lung injury. Our lab has shown that mature lung endothelial cells (ECs) can transdifferentiate into lymphocyte precursor–like cells (LCPs) in response to inflammatory stress—a process enhanced by loss of PTEN, a key inhibitor of the PI3K/Akt pathway. Building on these findings, my work investigates how PTEN, S1PR1, and TRPC6 signaling coordinate to regulate endothelial stability and fate decisions following injury. S1PR1 activation promotes Rac1-mediated adherens junction assembly and barrier protection, whereas TRPC6-mediated calcium influx increases permeability and inflammatory signaling. PTEN functions as a molecular brake on PI3K/Akt signaling, maintaining the balance between EC proliferation, survival, and plasticity. Together, these pathways form an integrated network that determines whether endothelial cells promote repair or contribute to dysfunction. Understanding their interplay may reveal therapeutic targets to restore vascular integrity and improve recovery from severe lung injury.