Glenn Radice, PhD
Mechanical forces play a critical role in regulating cellular function in all cell types. This is especially true in the heart where the contractile force generated by myocytes provides mechanical stimuli both to itself and to neighboring cells through mechanosensing structures, including the N-cadherin-catenin cell adhesion complex.
Research in Dr. Radice’s laboratory is directed at uncovering the molecular, biochemical and cellular basis for how heart muscle cells sense and respond to mechanical force. Shortly after birth, muscle cells of the mammalian heart lose their ability to divide. Thus, they are unable to effectively replace dying cells in the injured heart. Previous work has established that abnormal mechanotransduction in the neonatal mouse heart, caused by depletion of N-cadherin-associated a-catenins, results in sustained myocyte proliferation into adult life. Current research emphasis is to identify how N-cadherin together with the underlying cytoskeleton transmits force into the cell and activates signaling events that control myocyte proliferation. The goal of our studies is to provide an understanding of how mechanotransduction regulates myocyte proliferation in the normal heart, and apply this knowledge to the design of novel therapies to stimulate adult myocytes to undergo cell division and repair the injured heart. To study this phenomenon the lab employs a multidisciplinary approach, including mouse molecular genetics, cell biology, cardiac physiology, and biomechanical techniques. In addition to providing mechanical coupling between myocytes, cell adhesion complexes are critical for normal electrical activity in the heart. Another major project investigates how defects in intercellular adhesion and signaling cause heart disease, including arrhythmogenic cardiomyopathy. To understand the molecular mechanisms underlying the pathogenesis of this disease, genetically modified animal models are being created that better represent the genotype-phenotype relationship of the human disease.
Xiafei Li, PhD
Post Doctoral Research Associate
Rhode Island Hospital
Evelyn Tolbert, MS
Senior Research Associate
Rhode Island Hospital