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Wandi Zhu, Phd
April 26 @ 12:00 pm - 1:00 pm
Brigham and Women’s Hospital
Harvard Medical School
MECHANOELECTRICAL SIGNALING IN THROMBOTIC COMPLICATIONS OF CARDIOMETABOLIC DISEASE
Thrombosis is a major complication of cardiometabolic disease and a leading cause of mortality globally. Vascular abnormalities, as a result of cardiometabolic dysregulation, lead to disordered blood flow and increased shear stress on both blood and endothelial cells. Thrombosis often occurs in these conditions, but the cellular mechanisms mediating mechanical contributions to thrombosis and hemostasis are poorly understood. One of the major mechano-transducers in blood and endothelial lineages is the mechanosensory ion channel, Piezo1. Using a perturbational screening of patient peripheral blood samples for latent phenotypes, I identified an elevated Piezo1 expression and function in multiple blood lineages in diabetes, which contribute to a novel mechanically driven thrombotic pathway. The upregulation of Piezo1 in diabetes was partly due to hyperglycemia, which caused an increase in Piezo1 transcription in mature blood cells, as well as selects for high-Piezo1- expressing progenitors during hematopoiesis. Understanding the mechanical component of thrombosis and how it is coupled to metabolism will allow us to isolate disease-associated thrombotic triggers from the general coagulation pathways, thus enabling the development of urgently needed precision therapies without bleeding complications. The findings also establish the basis for exploring mechanoelectrical signaling through ion channels in non-excitable cell types, such as blood and endothelial cells, regulating blood clotting, inflammation, and hematopoiesis.
Wandi received her BS in Biomedical Engineering from Stony Brook University in 2013 and PhD in Biomedical Engineering from Washington University in St. Louis in 2018. After a brief work experience at Genentech, she joined Dr. Calum MacRae’s lab in 2019 for her postdoctoral training in Cardiovascular Medicine at Brigham and Women’s Hospital. With her background in engineering and cellular electrophysiology, Wandi is interested in applying interdisciplinary approaches to reveal the roles of mechanoelectrical signaling in both excitable and non-excitable cell types in health and cardiovascular diseases, as well as establish means to conduct personalized risk assessments and therapeutic testing.