BME Seminar Series: Dr. James Smyth, Virginia Tech
James William Smyth, PhD
Assistant Professor, Virginia Tech Carilion Research Institute
Assistant Professor, Center for Heart and Regenerative Medicine Research, Virginia Tech Carilion Research Institute
Assistant Professor, Department of Biological Sciences, Virginia Tech
Assistant Professor, Department of Biomedical Sciences, Virginia Tech Carilion School of Medicine
"Regulation of gap junction function at the RNA level; stressed hearts and mixed messages"
Altered expression and localization of the gap junction protein connexin43 occurs in several diverse pathologies, and directly contributes to the arrhythmias of sudden cardiac death. We have found that dynamic regulation of connexin43 at the point of translation occurs, yielding truncated protein isoforms regulating gap junction formation. Using cellular trans-differentiation and viral infection as model systems where protein translation initiation is altered, we are uncovering novel mechanisms of global and gene-specific regulation of protein synthesis. We have identified dynamic expression of distinct connexin43 mRNA transcripts differing only in 5’UTR length. These transcripts are subject to alternative translation initiation events ultimately regulating gap junction formation in stress and aging. Together, our findings elucidate a relationship between mRNA transcript isoform expression and translation initiation regulating intercellular communication. Our goal is to harness translation initiation to restore normal connexin43 function and electrical coupling in diseased hearts.
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 Assistant Professor in the Department of Biological Sciences.