Webinar Featuring Young-Kwon Hong, Ph.D.

Description

Our May webinar will feature Young-Kwon Hong, Ph.D., Assistant Professor, Department of Surgery, Vascular Biology Beth Israel Deaconess Medical Center. Dr. Hong will present his talk entitled, "Mechanism of Lymphatic Mechanotransduction and Potential Therapeutic Applications to Abnormal Brain Fluid Accumulation." Abstract: Lymphatic vessels are essential for tissue fluid homeostasis, yet how mechanical forces regulate lymphatic function and drainage remains poorly defined. We investigated the role of the mechanosensitive ion channel Piezo1 in lymphatic endothelial cells (LECs) and its impact on lymphatic transport and brain fluid clearance. We show that fluid flow activates Piezo1, inducing calcium influx and downstream signaling through Orai1, KLF2, and Prox1 to regulate lymphatic vessel behavior. Piezo1 activation promotes both rapid increases in lymphatic permeability and longer-term lymphangiogenic responses. Using in vivo mouse models and lymphatic-on-chip systems, we demonstrate that pharmacologic activation of Piezo1 enhances lymphatic drainage and accelerates interstitial fluid transport. Importantly, activation of lymphatic Piezo1 significantly improves cerebrospinal fluid clearance via meningeal lymphatics and reduces disease severity in a mouse model of hydrocephalus, including decreased ventricular enlargement and improved functional outcomes. Collectively, these findings identify Piezo1 as a central regulator of lymphatic mechanotransduction and suggest that targeting Piezo1 may provide a therapeutic strategy for disorders associated with impaired fluid clearance in the brain.