J. Carter Ralphe, MD, professor, Division of Cardiology, received $2,417,136 from the National Heart, Lung, and Blood Institute to support his new R01 project, “Mutation-specific Responses to Myosin Inhibitors in Human iPSC Models of HCM.” Co-investigators include Willem (Toy) De Lange, PhD, scientist II, and Emily Farrell, PhD, scientist II, both members of the Division of Cardiology. The project will focus on how specific mutations that cause human hypertrophic cardiomyopathy (HCM) respond to the novel myosin inhibitor class of therapeutics. Ralphe’s team will leverage a human iPSC cardiac tissue model and selected mouse models to perform detailed functional assessment and analyses of cellular transcription and proteome responses. These data will support future refinement in how these therapies are applied in patients with HCM, improving efficacy in selected individuals, improving safety, and reducing costs through avoidance of inappropriate use. Additionally, the mutation-specific pathophysiology identified through this work will address an increasingly recognized gap in knowledge about how specific mutations lead to the HCM phenotype. This information will be critical in the search for more effective therapies. The four-year project began on September 1, 2026.