James Smyth, Ph.D.

One of the most important mechanisms of intercellular communication is through structures known as gap junctions, which are formed by proteins and directly couple cell interiors. In the working myocardium of the cardiac ventricle, connexin 43 (Cx43) is the primary isoform. These Cx43 gap junctions electrically couple cardiac muscle cells and are responsible for the proper beating of the heart. In most forms of heart disease, altered expression of Cx43 interferes with the heart’s electrical system, fostering arrhythmia and sometimes triggering sudden cardiac death.

The Smyth Laboratory uses molecularly tractable model systems to understand how the heart responds to injury, from localized infarctions and ischemia to infection of the heart by viruses such as adenovirus. Using state-of-the-art molecular, biochemical, and imaging technologies, Smyth Lab researchers determine the molecular changes that occur during disease responsible for reduced gap junction formation. They investigate how regulation of protein synthesis, at the point of mRNA translation influences gap junction formation.

This emerging field of alternate translation initiation is subject to dynamic regulation through signal-transduction networks in the cell, which scientists are interrogating biochemically. Live-cell fluorescence confocal microscopy enables us to watch these events in real time and understand how cardiac cells respond to such stresses as hypoxia and viral infection. With super-resolution microscopy, researchers are also probing connexin biology at a resolution of 20 nanometers, providing previously unattainable and exciting insights at the molecular level.