James A. Spudich

This study shows that the E525K β-myosin mutation reduces cardiomyocyte contraction without altering crossbridge cycling, through structural and computational analysis.

This study shows that myosin inhibition with mavacamten is effective in treating HCM caused by both truncating and missense variants in MYBPC3, despite different pathomechanisms.

This paper studies the G768R mutation in cardiac myosin, showing it increases the duty ratio to >60%, leading to hypercontractility and impaired relaxation.

This study investigates how HCM mutations Y115H and E497D disrupt the folded-back state of human beta-cardiac myosin, leading to hypercontractility by destabilizing the OFF-state.

This study investigates how the G256E HCM mutation affects myosin function by altering nucleotide handling, leading to prolonged relaxation and contributing to hypertrophic cardiomyopathy.

The paper develops a FRET assay to directly quantify the IHM state of human β-cardiac myosin and shows how mutations and perturbations affect its stability.

This study uses cryo-ET to analyze the structure of thin filaments in human iPSC-derived cardiomyocytes and how they change with disease-related perturbations.

This study investigates the effects of the MYH7 G256E mutation on myosin function across multiple scales, finding increased hypercontractility and mitochondrial respiration.

This study investigates how HCM mutations R403Q and R663H in myosin cause hypercontractility by increasing functionally-accessible myosin heads and affecting MyBP-C binding.