Determining mechanistic effects of therapeutic compounds aimed at treatment of heart failure

The proposed research aims to determine mechanistic effects of therapeutic compounds aimed at treatment of heart failure. We will specifically determine the activating shifts in kinetics and structural dynamics induced by these compounds on ATP-dependent calcium transport. This transport is carried out by SERCA proteins and is essential to heart muscle relaxation and has been identified as central to heart failure, which today is the leading cause of hospitalization world-wide. The proposed research constitutes a novel approach to track mechanisms of action of activating compounds with therapeutic effects for heart failure, which paves way for development of “smart” drugs with high specificity. Such drugs would enable immediate and non-invasive administration at hospitals and have potential for long-term usage to improve cardiac performance.