James Spudich

Co-Founder & Member of Scientific Advisory Board, Cytokinetics

Search every verified James Spudich interview, podcast appearance, and on-the-record quote — each transcript cross-checked by AI and human review to confirm speaker identity. James Spudich, a professor of medicine at Stanford University and co-founder of Cytokinetics, has continued to discuss the translational research pathway from basic muscle biology to therapeutic development. In a December 2023 talk, he described how his laboratory's fundamental studies of myosin, the motor protein driving muscle contraction, led to the discovery that hypertrophic cardiomyopathy (HCM) mutations cause hypercontractility by increasing the number of myosin heads that can interact with actin. He noted that about half of cardiac myosins are normally in a folded-back, inactive state, and that HCM mutations shift this equilibrium toward the active state. Spudich recounted that this work led to the founding of MyoKardia and the development of mavacamten, a small-molecule myosin inhibitor that received FDA approval after Bristol-Myers Squibb acquired the company. He stated that patients on the therapy reported transformative improvements, such as being able to walk marathons. Spudich has also emphasized the importance of sustained basic research funding, noting that his laboratory has received NIH support for five decades. In earlier lectures, he reviewed the history of muscle biology, describing the swinging crossbridge hypothesis and the development of single-molecule laser trap assays that measured the 10-nanometer step and 2-piconewton force of a single myosin molecule. He has discussed the "myosin mesa" hypothesis, which proposes that a flat surface on myosin serves as a binding platform for regulatory interactions, and that many HCM mutations disrupt electrostatic interactions that keep myosin heads in an off state. Spudich has argued that understanding these molecular details makes it possible to design small-molecule therapies that correct the power output changes caused by cardiomyopathy mutations.