Research Summary
Understand the regulatory dynamics of “resilience networks” during development, healthy aging and disease models.
We received a 2022 Catalyst Award that focused on understanding the molecular mechanisms by which HDAC inhibition promotes neuronal resilience. This project began with the striking observation that loss of a SIN-3/HDAC complex could rescue morphological phenotypes in both stressed C. elegans and mouse cortical neurons. We identified three distinct paradigms in which we found HDAC inhibition (HDACi) to be protective, and with the support of the Knight Initiative we sought to understand how HDAC inhibition improves neuronal resilience against stress. In our 2022 proposal, we defined three aims that have guided our work over the past two years. In brief, our goals were to (1) uncover mechanisms by which HDACi protects against ER stress, (2) uncover mechanisms by which HDACi protects against endosomal stress, and (3) identify a conserved “resilience network” that could protect neurons during stress or aging across evolution. We have made significant progress on all aims, and hope to advance this project with this research award.
