Research

Research Interests

• AAA+ Protein Mechanisms: Investigating the molecular mechanisms of AAA+ proteins—including Hsp104, p97/VCP, and Thorase/ATAD1, along with their potentiated or disease-associated variants.

• Molecular Chaperones and Disaggregases: Identifying, characterizing, and engineering novel disaggregases, chaperones, and related biomolecules that maintain or restore protein and genome homeostasis. Our work targets aberrant protein aggregation of α-synuclein, transthyretin (TTR), TDP-43, and FUS, which are implicated in Parkinson’s disease (PD), Alzheimer’s disease (AD), AD-related dementias (ADRD), amyloidosis, atherosclerosis, hypertrophic cardiomyopathy (HCM), and amyotrophic lateral sclerosis (ALS).

Mechanistic Focus

1. AAA+ Protein Function: Dissecting conformational dynamics, substrate recognition, and cofactor regulation of Hsp104, p97/VCP, Thorase/ATAD1, and their variants using single-molecule and structural approaches.

2. Discovery and Evolution of Molecular Machines: Identifying and evolving novel disaggregases, chaperones, and related factors that govern proteostasis and genome stability, with emphasis on mechanistic principles and emergent properties.

3. Sequence Grammar of Aggregation-Prone Proteins: Exploring how mutations, isoforms, and post-translational modifications reshape folding landscapes and aggregation kinetics of α-synuclein, transthyretin, TDP-43, and FUS.