James Smyth, Ph.D.
“We study how protein translation and intercellular communication are altered in disease. Viruses have evolved alongside us to exploit these same systems, revealing critical control points we can target as therapeutic opportunities across diverse pathologies.”
Investigating pathological changes to intercellular communication
What are the critical mechanisms regulating cell communication in health and disease?
Events that stress the heart, including ischemia and viral infections, disrupt communication between heart muscle cells, creating underlying abnormalities that generate irregular heart rhythms. James Smyth and his team focus on electrical connections between heart muscle cells, called gap junctions, formed by the protein connexin 43 (Cx43). In essentially all forms of cardiomyopathy, loss or altered regulation of Cx43 occurs and results in impaired electrical conduction and contributes to sudden cardiac death. The team's over-arching goal is to identify critical therapeutic targets to restore or preserve normal electrical coupling in diseased hearts and prevent the arrhythmias of sudden cardiac death.
The lab is also extending this work to cancer, where different forms of Cx43 and its functions contribute to altered cell signaling, invasive behavior, and therapeutic resistance.
As molecular virologists, Smyth and his team also study how respiratory viruses such as adenovirus and coronavirus affect the heart and replicate themselves. The team is investigating specifically how viruses reprogram the cell at the molecular level to harness this information therapeutically for myocarditis and beyond.
Using a combination of RNA biology, biochemical assays, live-cell imaging, and super-resolution microscopy, the Smyth Lab aims to uncover new therapeutic strategies to restore electrical integrity in the injured and infected heart.
smythj@vtc.vt.edu
540-526-2238
R-2116, Riverside 2
- Associate Professor, Fralin Biomedical Research Institute at VTC
- Associate Professor, Department of Biological Sciences, College of Science
- Associate Professor, Department of Basic Science Education, School of Medicine
Padget RL, Zeitz MJ, Blair GA, Wu X, North MD, Tanenbaum MT, Stanley KE, Phillips CM, King DR, Lamouille S, Gourdie RG, Hoeker GS, Swanger SA, Poelzing S, and Smyth JW. Acute adenoviral cardiac infection elicits an arrhythmogenic substrate prior to myocarditis. Circulation Research. 2024 Mar 29;134(7):892-912. doi: 10.1161/CIRCRESAHA.122.322437. Epub 2024 Feb 28. PMID: 38415360; PMCID: PMC11003857.
Calhoun PJ, Phan AV, Taylor JD, James CC, Padget RL, Zeitz MJ, Smyth JW. Adenovirus targets transcriptional and posttranslational mechanisms to limit gap junction function. The FASEB Journal. 2020 Jul;34(7):9694-9712. doi: 10.1096/fj.202000667R. Epub 2020 Jun 2. PMID: 32485054; PMCID: PMC7501180.
Zeitz MJ, Calhoun PJ, James CC, Taetzsch T, George KK, Robel S, Valdez G, Smyth JW. Dynamic UTR usage regulates alternative translation to modulate gap junction formation during stress and aging. Cell Reports. 019 May 28;27(9):2737-2747.e5. doi: 10.1016/j.celrep.2019.04.114. PMID: 31141695; PMCID: PMC6857847
James CC*, Zeitz MJ*, Calhoun PJ, Lamouille S, Smyth JW. Altered translation initiation of Gja1 limits gap junction formation during epithelial-mesenchymal transition. Molecular Biology of the Cell. 2018 Apr 1;29(7):797-808. doi: 10.1091/mbc.E17-06-0406. PMID: 29467255; PMCID: PMC5905293.
Smyth JW and Shaw RM. Autoregulation of connexin43 gap junction formation by internally translated isoforms. Cell Reports. 2013 Nov 14;5(3):611-8. doi: 10.1016/j.celrep.2013.10.009. Epub 2013 Nov 7. PMID: 24210816; PMCID: PMC3898934
University of California, San Francisco
Specialist
Cedars-Sinai Heart Institute, Los Angeles
Project Scientist
- Trinity College Dublin: Ph.D., Virology
- University of California, San Francisco: Postdoctoral fellowship
- University College Dublin: B.S., Microbiology
- Faculty Mentor Award, Virginia Tech Office of Postdoctoral Affairs, 2024
- Principles of Community Award, Virginia Tech Department of Biological Sciences, 2023
- Faculty Service Award, Virginia Tech Department of Biological Sciences, 2021
- Honoring Exemplary Researcher Outreach (H.E.R.O.) Honoree, Roanoke Valley Governor’s School, 2019
- Invited ‘Emerging leader’ Keynote Speaker, International Gap Junction Conference, Glasgow, United Kingdom, 2017
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Summer research fellows showcase studies at annual symposium , article Date: Aug 25, 2025 - -
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Article ItemFralin Biomedical Research Institute scientist to co-chair international forum on gap junctions , article
Co-chairs James Smyth and Silvia Penuela are bringing scientists from across the globe to Arlington to share findings in a rapidly developing field whose insights point to novel therapeutic opportunities in a wide range of disorders and complex diseases.
Date: May 24, 2024 - -
Article ItemUnveiling a hidden threat: Researchers show viral infections pose early heart risks , article
Fralin Biomedical Research Institute scientists challenge traditional assumptions and open a new window to help people with cardiac infections.
Date: Mar 07, 2024 - -
Article ItemSeeking a better understanding of how genetic mutations lead to developmental disorders , article
A new Fralin Biomedical Research Institute award for postdoctoral scholars will help Chelsea Phillips advance research related to cellular junctions in heart cells.
Date: Nov 16, 2023 - -
Article Item‘The real deal’: Students thrive and grow in summer hands-on research experiences , article
This was the seventh summer of programs aimed at engaging and training the next generation of scientists. This year, 34 students from colleges in Virginia, North Carolina, and as far away as California, and from five area high schools, participated in summer undergraduate research fellowship programs at the Fralin Biomedical Research Institute at VTC.
Date: Sep 20, 2023 - -
Article ItemResearch project shows medical student the power of perseverance , article
Ellen Shrontz is one of nine students at the Virginia Tech Carilion School of Medicine to earn a Letter of Distinction for her four-year research project. Her research focused on gap junctions, specialized intercellular connections, that are lost in many forms of heart disease and during cancer progression.
Date: Mar 10, 2023 - -
Article ItemThree translational biology, medicine, and health graduate students awarded American Heart Association fellowships , article
The awards are intended to enhance the research and clinical training of promising students seeking careers as scientists, physician-scientists, or clinician scientists interested in improving global cardiovascular, cerebrovascular, and brain health.
Date: Jan 11, 2023 - -
Article ItemAmerican Heart Association grant will support undergraduates interested in pursuing cardiovascular research , article
Select students will tackle cardiovascular research projects under the mentorship of Fralin Biomedical Research Institute scientists. Applications are due Feb. 14.
Date: Jan 04, 2023 - -
Article ItemCardiovascular scientists to explore viral infection that can lead to sudden death , article
James Smyth, associate professor at the Fralin Biomedical Research Institute at VTC, has been awarded a five-year, $2.7 million grant from the National Institutes of Health to discover why viruses that normally infect our lungs can turn deadly when they infect the heart.
Date: Nov 18, 2022 - -
Article ItemFralin Biomedical Research Institute expands Summer Undergraduate Research Fellowship program , article
More than 30 undergraduate and high school students worked behind the curtain of biomedical research this summer at the Fralin Biomedical Research Institute at VTC.
Date: Aug 16, 2022 - -
Article ItemFralin Biomedical Research Institute at VTC Center for Vascular and Heart Research holds retreat to catalyze collaboration , article
The daylong retreat at The Hotel Roanoke & Conference Center and on the research institute campus included presentations by research teams about their lab’s key techniques, competencies, and equipment.
Date: Jul 21, 2022 - -
Article ItemDual degree program and NIH grant allow medical student to pursue doctorate before graduation , article
Kenneth Young is pausing his studies the Virginia Tech Carilion School of Medicine to pursue a doctorate through Virginia Tech’s Translational Biology, Medicine, and Health Graduate Program, with his first year of research funded by a National Institutes of Health Diversity Supplement grant.
Date: Oct 20, 2021 - -
Article ItemFralin Biomedical Research Institute Summer Undergraduate Research Fellows present neurobiology and advanced imaging findings , article
The Fralin Biomedical Research Institute at VTC hosted 20 undergraduate students this summer for a 10-week experience in two research programs that explore neurobiology and cutting-edge imaging technology to visualize living systems.
Date: Aug 24, 2021 - -
Article ItemFralin Biomedical Research Institute scientists confirm usually benign virus attacks the heart’s electrical system , article
Virginia Tech researchers made their findings via first-of-their-kind experiments to observe adenovirus effects on human heart cells in a culture dish.
Date: Jun 16, 2020 - -
Article ItemFralin Biomedical Research Institute doctoral candidate awarded NIH Fellowship to study role of virus in sudden cardiac death , article
A dose of adenovirus hits most people like a common cold – a cough, a fever, maybe a sore throat. But for an unfortunate few, the usually benign bug hacks the heart’s cellular electrical communication system and sometimes proves fatal.
Date: May 08, 2020 - -
Article ItemRoanoke scientists give local youth behind-the-scenes look at biomedical research , article
For the second year, Roanoke youth enrolled in Goodwill Industries of the Valley's YouthHQ@Goodwill Science Camp visited the Fralin Biomedical Research Institute at VTC this week. The campers learned about careers in science, microscopy, genetics, viruses, and how a heartbeat happens.
Date: Aug 08, 2019 - -
Article ItemLost in translation: The medium is the message for a healthy heartbeat , article
Researchers at the Fralin Biomedical Research Institute at VTC have revealed how a genetic message to produce healthy heart tissue is altered in the body during stress and aging to contribute to sudden cardiac death.
Date: May 28, 2019 - -
Article ItemThe heart: digital or analog? VTCRI researchers shed dramatic new light on disorders of heart bioelectricity , article
Scientists at the Virginia Tech Carilion Research Institute have found evidence that may disrupt conventional understanding about how electrical activity travels in the heart — a discovery that potentially can lead to new insight into medical problems, such as heart arrhythmia and sudden cardiac death.
Date: Aug 27, 2018 - -
Article ItemHeart association to support VTCRI biological sciences grad student's research into sudden cardiac death , article
Patrick Calhoun is investigating how a viral infection that causes a mild cough in the lungs may have a much more severe effect in heart tissue.
Date: Aug 03, 2018 - -
Article ItemVTCRI scientists identify novel cellular mechanism that can lead to cancer metastasis , article
Scientists at the Virginia Tech Carilion Research Institute have added a new dimension to the understanding of how cells alter their communication with one another during development, wound healing, and the spread of cancer.
Date: May 29, 2018 - -
Article ItemTBMH graduate students land elusive National Institutes of Health fellowships , article
Doctoral students Tristan Raisch and Carissa James have won National Institutes of Health research fellowships aimed at protecting people with heart problems.
Date: Jan 08, 2018 - -
Article ItemVTCRI summer undergraduate neuroscience research federally funded for five more years , article
A summer pilot program for undergraduate neuroscience research at the Virginia Tech Carilion Research Institute proved so successful that National Institute of Neurological Disorders and Stroke, of the National Institutes of Health, has provided $500,000 of funding for another five years.
Date: Jan 04, 2018 - -
Article ItemUndergraduates will spend summer learning what it means to be biomedical research scientists in and out of the lab , article
SURF students in both programs will complete independent research projects, with guidance provided by VTCRI faculty mentors, to be presented at the Virginia Tech Undergraduate Research Symposia on July 27.
Date: Jun 13, 2017 - -
Article ItemVirginia Tech Carilion Research Institute scientist awarded $2.1 million to fight heart disease , article
Steven Poelzing, an associate professor at the institute, will lead a research team to investigate how the microscopic spaces surrounding heart cells affect connections called gap junctions, which allow electrical impulses and small molecules to pass between cells.
Date: Jan 10, 2017 - -
Article ItemInaugural heart school events will get rescheduled , article
The public is invited to learn more about heart development and current cardiovascular research during Virginia Tech Carilion Research Institute’s first heart school, held as part of American Heart Month.
Date: Feb 23, 2015 - -
Article ItemVirginia Tech Carilion Research Institute sets a new pace in heart research , article
The Virginia Tech Carilion Research Institute, well known for its innovative, world-class brain research, is launching a major new initiative in cardiovascular research.
Date: May 20, 2014 -
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