L. Michel Espinoza-Fonseca

I have extensive formal training and practical experience in molecular simulation of biomolecules andmedicinal chemistry. In the years that I have been an independent investigator, I have focused on thestructural basis of sarcoplasmic reticulum (SR) Ca2+ transport in the heart. In particular, I study thesarco/endoplasmic reticulum calcium Ca2+-ATPase (SERCA) and its regulation by the small transmembraneprotein phospholamban (PLB). Inhibition of SERCA by PLB is a hallmark of heart failure, thus the interactionbetween SERCA and PLB has become an attractive therapeutic target. While many functional aspects ofSERCA and PLB are known, many detailed questions remain concerning the structural basis of SERCAactivation and inhibition by PLB: How do SERCA couples structural dynamics with activation? What step(s)along the catalytic cycle of the pump is inhibited by PLB? What are the mechanisms of SERCA relief ofinhibition by Ca2+ and PLB phosphorylation? To answer these questions, my group uses a combination ofstate-of-the-art computer simulations and analysis techniques. The work in my lab is closely coupled toexperimental studies through collaborations with world-class FRET and NMR spectroscopists who arestudying SERCA and PLB.