Su-Hyuk Ko, Ph.D.

Pathological autophagy as a driver of 4R tau propagation and neurotoxicity in tauopathies
Dr. Su-Hyuk Ko’s research focuses on the role of dysregulated autophagy in the progression of tauopathies, with a particular emphasis on 4-repeat (4R) tau isoforms that accumulate in Alzheimer’s disease and related disorders. He investigates how autophagy, under chronic proteostatic stress, shifts from a degradative process to a secretory mechanism that facilitates the release and intercellular propagation of tau. Using C. elegans transgenics, rodent neuronal cultures, and in vivo tauopathy models, his team aims to define stage-specific mechanisms through which pathological autophagy exacerbates tau burden and neurodegeneration. These studies aim to identify actionable points for therapeutic intervention by targeting autophagic flux at specific stages of disease progression.
 

Redox-sensitive axonal fusion and regenerative reprogramming following neural injury
In parallel, Dr. Ko studies how injured neurons regain structural and functional connectivity through axonal fusion, a membrane repair process distinct from classical axon regeneration. He has demonstrated that lipid peroxidation promotes the phase separation of PSR-1, a phosphatidylserine receptor that initiates fusion-like events between damaged axonal membranes. Ongoing work in C. elegans and mammalian nerve injury models aims to delineate the molecular cues that regulate fusion competence, with a particular focus on redox signaling and membrane lipid remodeling. These efforts are geared toward developing translational strategies for enhancing recovery after peripheral or central nervous system trauma.
 

Together, these two research programs converge on a common goal: to elucidate how neuronal self-preservation and repair mechanisms become maladaptive under disease or injury conditions, and how they might be redirected for therapeutic benefit.