Drs. Luo and Lacroix Awarded $2.5M NIH Grant for Groundbreaking PIEZO1 Mechanotransduction Research

Congratulations to Dr. Yun Lyna Luo, A Professor in the Department of Biotechnology and Pharmaceutical Sciences in the College of Pharmacy, and Dr. Jerome Lacroix from the Department of Biomedical Sciences in the College of Osteopathic Medicine of the Pacific, on receiving an NIH R01 grant award totaling $2,514,288 from the National Heart, Lung, and Blood Institute (NHLBI) for their research project, “Cooperative Modulation of Piezo Channels”. This is the third NIH R01 grant that Drs. Luo and Lacroix have secured together as Multi-PIs (MPI) at WesternU since 2019.

Grant Summary: PIEZO1, an important molecular sensor in our cells, plays a crucial role in detecting mechanical forces, and its malfunction has been implicated in various cardiovascular pathologies including hypertension, xerocytosis, dilated cardiomyopathy, and lymphedema. Here, to gain a better understanding of PIEZO1 functioning, we investigate how its unique protein shape influences the functioning and interactions of neighboring PIEZO1 sensors. This MPI project is a joint effort with Dr. Medha Pathak from UC Irvine School of Medicine. In Aim1, we use multi-scale molecular dynamics simulations to study the energetics and dynamics of PIEZO footprint-footprint interactions in large membranes. In Aim2, we use high-speed single molecule Ca2+ imaging to map the mobility and activity of endogenous PIEZO1 channels expressed at the surface of endothelial cells derived from human induced pluripotent stem cells. This will allow us to examine cooperativity between neighboring channels under physiological conditions. In Aim3, we use high-resolution patch clamp electrophysiology to precisely quantify cooperativity by comparing the distributions of multi-channel open probabilities to binomial distributions expected for independent channels. If successful, this project will establish PIEZO1 cooperativity as a potential mechanism to contextually regulate mechanotransduction signaling, enhancing our understanding of its role in cardiovascular health and disease.