Area of Doctoral Study: Molecular Medicine
Undergraduate Institute: University of Maryland, College Park
Research Advisor: Martin Schneider, Ph.D.
Description of Research
Skeletal muscle is quickly activated after membrane depolarization by a large intracellular release of Ca2+ ions from the sarcoplasmic reticulum (SR). My lab studies the three steps in the activation mechanism for Ca2+ release in single isolated skeletal muscles: (1) Activation of membrane voltage sensor molecules, studied using a combination of electrophysiological (gating current) and genetic manipulations (siRNA, transgenic mice); (2) Opening patterns of individual Ca2+ release channels or a group of functionally linked release channels (e.g. RYR1 and DHPR) in response to stimulation, detected by high speed confocal microscopy; (3) The mechanism coupling the voltage sensor to the release channels, studied by pharmacological and biochemical manipulation in functioning fibers. My focus has been on S100A1 and Calmodulin (CaM) two modulators of skeletal muscle Ca2+ signaling. Our studies suggest that S100A1, similar to CaM, binds to different regions within the RyR1, but also indicates that S100A1 could bind to other target proteins. Where and how exactly S100A1 exerts these additional effects is currently unknown.