RUI: Mathematical modeling of innate antiviral and inflammatory responses for viral myocarditis

Viral myocarditis is a condition in which a viral infection causes inflammation and damage to the heart muscle, reducing its ability to pump blood and, in severe cases, leading to long-term heart disease or heart failure. Current treatments are limited because they often address infection or inflammation broadly, rather than the specific processes that determine whether the heart heals or develops lasting damage. This project will integrate mathematical modeling with laboratory experiments to examine how cardiac and immune cells communicate during early viral infection and to identify which interactions support healing and which, when dysregulated, contribute to harmful inflammation and long-term heart damage. The work has the potential to impact biotechnology by generating computational tools and experimentally testable predictions that can support the development, evaluation, or repurposing of more targeted strategies for virus-associated heart inflammation. Other features include providing hands-on interdisciplinary research training for undergraduate students in mathematics, biology, and related fields, and strengthening collaborative science through mentoring, course development, conference presentations, and hosting a regional STEM conference for undergraduate students. This project will develop and analyze a mathematical model of innate antiviral and inflammatory dynamics during viral myocarditis, supported by wet laboratory experiments. The model will explicitly represent the virus, cardiomyocytes, cardiac fibroblasts, macrophages, antiviral and pro-inflammatory signaling, and cardiac tissue damage using a system of coupled ordinary differential equations. The research has two main goals: (i) formulate, parameterize, analyze, and experimentally validate a model that captures the distinct and interacting contributions of cardiac-resident and recruited immune cells during viral infection of the heart; and (ii) use the model to investigate treatment-related questions involving the timing, magnitude, and cellular sources of antiviral and inflammatory responses. Sensitivity analysis and numerical simulations will identify key parameters and pathways that regulate viral clearance, excessive inflammation, and progression toward tissue damage. Cellular and molecular assays will guide model construction, inform parameter estimation, and test model-generated predictions about how specific immune pathways influence infection outcomes across heterogeneous cardiac cell populations. The resulting framework will address a gap in viral myocarditis research by providing a quantitative, cell-type-informed model of host-virus-immune interactions in the heart. In addition to advancing mathematical biology through the analysis of high-dimensional nonlinear dynamical systems, this project will generate experimentally grounded hypotheses about pathways that may be targeted to promote viral clearance while limiting harmful inflammation. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.