Friday, April 26, 2024
4/26/2024
Project Summary The ability of skeletal muscle to respond to changes in the metabolic environment and to supply energy in response to stress is essential for global metabolic health. At the onset of energetic stress, there is a change in substrate availability and molecular signals, including reactive oxygen species (ROS). ROS are important cell signaling molecules that are involved in both physiological and pathological development. One significant producer of ROS is Nadph oxidase 4 (Nox). Nox4 is unique compared to other Nox members as it predominantly produces hydrogen peroxide (H2O2), the most stable form of ROS. This project will focus on the assessment of in vivo and in vitro Nox4-mediated metabolic adaptations utilizing novel approaches including somatic gene transfer, transgenic mouse lines and high-resolution respirometry. In this proposal I will evaluate the role of Nox4 in energetic sensing and initiation of the metabolic stress response in skeletal muscle. This work will contribute to our understanding of physiological ROS and its downstream targets and will also assess a novel role for Nox4 in mediating mitochondrial adaptations to stress. Completion of this proposal will prepare me for a postdoctoral fellowship and an academic position by improving my technical skills, fostering collaborations, and implementing feedback in order to translate this proposal into a published scientific manuscript.
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