Brenda Russell, PhD
Department of Physiology and Biophysics
College of Medicine
Building & Room:
The goal of the Russell team is to understand cardiac remodeling in health and disease, which is almost certain to involve mechano-signaling and may provide a path for novel therapeutic targets to avoid heart failure over time.
Research Currently in Progress
Fundamental mechanobiology questions are how changes in load and strain link mechanosignaling pathways to actin assembly on heart muscle cells. We deliver local forces to heart cells in three dimensions and determine cellular changes using state-of-art biophysical, imaging, cell/molecular biology and proteomics. Techniques are refined on neonatal rat ventricular myocytes prior to use on myocytes derived from human induced pluripotent stem cells (hIPSC-CMs), and from human and adult rodent hearts. Our approach is to relate micromechanical signaling to cell hypertrophy by growing cells in microenvironments of different compliance (stiffness) to mimic chronic load (disease), or by loading mechanically to mimic acute changes. We focus on actin and the actin capping protein, CapZ, to study sarcomere assembly. The specific hypothesis currently being tested is that actin assembly depends on CapZ modification by mechano-transduction signaling pathways, such as deacetylation via HDACs, phosphorylation by PKCe, and binding to phosphatidylinositol 4,5-bisphosphate (PIP2).