STTR Phase I: Revealing Dangers in Heart Cells Using Multiple Molecular Sensors

The broader/commercial impact of this Small Business Technology Transfer (STTR) Phase I project seeks to address this limitation of predicting harmful effects on the heart by developing a live-cell screening platform. By focusing on cellular resilience capacity rather than static damage measurements, the project aims to establish a more predictive method. The project will also advance scientific understanding of how the cell's internal defense systems influence cellular resilience in cells. The proposed project will develop and evaluate a live-cell platform that simultaneously measures multiple internal stress-response pathways in heart cells derived from induced pluripotent stem cells. The project will integrate genetically encoded fluorescent biosensors that track oxidation-reduction activity across distinct cellular compartments in real time. The core concept mirrors a stress test, this platform applies a controlled oxidative challenge to damaged cells and measures how well cells recover. Recovery trajectories are then computationally analyzed to generate multidimensional cellular response fingerprints that reflect the cell's true functional resilience. Phase I objectives include engineering and validating a new mitochondria-targeted fluorescent biosensor, optimizing multiplexed sensor delivery, and evaluating whether these recovery profiles can reliably distinguish compromised physiological states. The anticipated outcome is a feasibility demonstration of resilience-based functional profiling as a next-generation approach to cardiotoxicity screening. 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.