Research Focus

Protein Folding & Misfolding in Neurodegenerative Diseases

Proper protein folding is essential for cellular function. In the endoplasmic reticulum (ER), molecular chaperones and folding enzymes assist nascent polypeptides to achieve their native conformations. However, genetic mutations, environmental stress, or aging can disrupt this delicate process, leading to the accumulation of misfolded proteins—a hallmark of many neurodegenerative disorders.

Our Research Goals

We aim to elucidate the structural and mechanistic basis of protein misfolding and its clearance pathways, with a focus on:

• How disease-associated mutations impair folding kinetics and stability
• The role of ER-resident chaperones (e.g., BiP, calnexin) in triaging clients
• Cross-talk between ER quality control and cytosolic degradation systems

Key Methodologies

Our lab integrates multidisciplinary approaches:

• Structural Biology: Cryo-EM and X-ray crystallography of chaperone-client complexes
• Biochemistry: In vitro reconstitution of folding/degradation assays
• Cell Biology: Live-cell imaging, CRISPR-Cas9 gene editing, and proteostasis reporters
• Disease Models: Patient-derived iPSCs and transgenic mouse models

Current Projects

• Structural dynamics of mutant SOD1 in ALS pathogenesis
• Mechanism of tau aggregation suppression by Hsp70 co-chaperones
• Development of small-molecule correctors for α-synuclein misfolding in Parkinson’s disease

By bridging molecular mechanism with pathological relevance, we strive to identify novel therapeutic strategies that restore proteostasis in neurodegenerative conditions.