Targeting ubiquitin-mediated proteostasis to rescue motor nuron vulnerability in SBMA
Summary Description
Preliminary data from our lab indicate that lower motor neurons in SBMA fail to activate the ubiquitin–proteasome system (UPS), a critical neuroprotective protein quality control pathway, unlike other, less vulnerable spinal cord neurons. This project investigates the molecular basis of this selective UPS suppression in vulnerable motor neurons. Using single-nucleus epigenomic profiling and functional testing in Drosophila models, this work aims to uncover the mechanisms underlying UPS dysfunction and evaluate whether restoring this pathway can rescue disease phenotypes. The results will reveal novel potential therapeutic targets for SBMA and related neurodegenerative conditions.
Bio
Changwoo (Chris) Lee began his research in neurodegenerative disease as an undergraduate in Dr. Albert La Spada’s lab at University of California San Diego. He pursued his Ph.D. in Dr. Janghoo Lim’s lab at Yale University, where he continued his research in SBMA and other polyglutamine diseases through a combination of classical bench-top experiments and advanced computational analyses. His doctoral research also involved a close collaboration with Dr. Andrew Lieberman’s lab at the University of Michigan. Now as a postdoctoral researcher in the Lim lab, Chris is committed to investigating the cellular and molecular mechanisms underlying neurodegenerative diseases, with the long-term goal of translating mechanistic insights into therapeutic strategies.
