October 5
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12:00 PM
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1:00 PM
Iterating experiments and network modeling towards precision cardiology
Jeff Saucerman, PhD
Professor of Biomedical Engineering
Professor of Cardiovascular Medicine
University of Virginia
Abstract:
Cardiac hypertrophy can be adaptive with exercise but becomes harmful due to gene mutations or heart attacks, leading to heart failure. This complexity makes it hard to understand and target the molecular networks involved. In this study, we identified a patient with a unique mutation in MYBPC3 associated with hypertrophic cardiomyopathy, which we recapitulated in a knock-in mouse model. Next, a computational network model predicted that MYBPC3 mutation-induced hypertrophy is mitigated by the mTOR inhibitor rapamycin, which we validated in cell culture, the MYBPC3 mutant mouse model, and in two observational patient cohorts. This study illustrates how iteration between clinic, network models, and experimental validation can guide precision therapies.
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