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G protein-coupled receptors, abbreviated as GPCRs, are the largest membrane protein family with more than 800 members that are currently targeted by one-third of FDA approved medications, despite only 10% GPCRs have been subjected to drug development. My research focuses on understanding the GPCR activation and its molecular pharmacology for better drug discovery. 

By integrating 19F-NMR spectroscopy, cryo-electron microscopy, and molecular dynamics simulations, we identified an underexplored intermediate conformational state plays a significant role in the GPCR signaling, independently regulating a signaling process different from the other conformational states reported previously. 

This work not only advances the understanding of GPCR signaling mechanisms but also paves the way for a novel therapeutic strategy that specifically target disease-related receptor conformation.

Metabolic engineering optimizes cellular processes to produce bio-based chemicals, reducing reliance on fossil fuels and benefiting human and environmental health. My research develops orthogonal gene expression tools and designs pathways to convert inexpensive feedstocks, like glycerol and C1 compounds, into valuable chemicals, supporting a greener chemical industry.

A key challenge in metabolic engineering is balancing gene expression to avoid bottlenecks, especially in iterative pathways like reverse β-oxidation (rBOX). To address this, we developed the TriO system, a plasmid-based tool for controlled gene expression. By fine-tuning expression, we optimized enzyme combinations and achieved near-optimal butyrate production from glycerol in E. coli, reaching up to 90% of the theoretical yield.

In addition to optimizing existing pathways, we are engineering new pathways to convert C1 compounds into ethylene glycol and branched-chain products. C1 compounds like COâ‚‚ play a crucial role in reducing greenhouse gases and these methods offer sustainable alternatives to petrochemicals.

My research investigates tauopathies, a group of neurodegenerative diseases, including Alzheimer’s, driven by pathological tau aggregation in the brain. I focus on the role of molecular chaperones, critical regulators of protein homeostasis, in modulating tau aggregation. Through a medium-throughput screen of chaperone families, I identified several significant tau modulators, including the small isoform of DnaJB6, which demonstrated exceptional potency in reducing tau aggregation. Using cellular and in vivo models, I established that DnaJB6 overexpression not only mitigates tau pathology but also shows potential to potentially improve memory and behavior in a tauopathy mouse model. These findings address critical knowledge gaps and position DnaJB6 as a novel and promising therapeutic target for tauopathies. My ongoing research further explores DnaJB6’s mechanisms and broader implications in tau regulation, with additional publications in progress to contribute important advancements toward understanding and treating tau-related diseases.