BME Seminar Series: Dr. James Smyth, Virginia Tech

James W. Smyth Ph.D.
Associate Professor, Fralin Biomedical Research Institute at VTC and Virginia Tech School of Medicine
Associate Professor, Virginia Tech Center for Heart and Regenerative Medicine Research
Associate Professor of Biology, College of Science, Virginia Tech
Director, VTCRI Molecular Visualization Summer Undergraduate Research Fellowship program

Abstract: 

"Viral subversion of intercellular coupling: bridging the gap from mouse to human heart disease"

Myocarditis is a leading cause of sudden cardiac death and adenovirus is a major etiological agent underlying such cardiomyopathies. However, our understanding of adenoviral cardiac infection and resulting pathological changes leading to arrhythmias is limited, due to viral host species-specificity hindering disease model development. Intercellular junctions are critical to maintaining normal cardiac electrophysiology, with gap junctions comprising connexin proteins serving to directly couple cardiomyocytes and participate in a complex interplay with other junctional structures and ion channels to effect proper conduction. Gap junctions also facilitate propagation of cell-intrinsic and adaptive antiviral immune responses, but viral manipulation of these structures is largely unexplored. Using human induced-pluripotent stem cell derived cardiomyocytes complemented with epithelial cell assays, we have identified targeting of intercellular communication early in adenoviral infection through suppression of connexin protein expression and function. To translate our findings to the whole animal, we have developed a model of mouse adenoviral acute cardiac infection and myocarditis to understand viral and immune-mediated pathological mechanisms. By revealing how adenovirus subverts intercellular coupling to facilitate its replication and spread we aim to test antiviral interventions as well therapeutic approaches to restore normal electrical coupling in diseased hearts.

Bio: 

Jamie Smyth obtained a bachelor of science in microbiology at University College Dublin and PhD in virology at Trinity College Dublin, Ireland before pursuing postdoctoral training at the University of California San Francisco and later at Cedars Sinai Heart Institute. Translating a background in molecular virology to cardiovascular cell biology, he opened his laboratory in 2014 at the Fralin Biomedical Research Institute at Virginia Tech Carilion in Roanoke, Virginia where he is also an Associate Professor in the Department of Biological Sciences and Virginia Tech Carilion School of Medicine.