Research Vision

Our lab investigates the fundamental biophysical mechanisms by which metabolites maintain protein homeostasis across multiple scales - from molecular interactions in test tubes to cellular processes and whole organisms. We focus particularly on understanding these mechanisms in the context of aging and age-related diseases.

Core Research Questions

1.What role do micromolecules (metabolites) play in determining protein structure and quality control?

2. How does aging alter the cellular environment and affect protein folding and misfolding?

3. How do biotic and abiotic stressors trigger protein misfolding through altered metabolite-protein interactions?

We integrate longitudinal and cross-sectional cohort analyses with targeted laboratory studies, bridging population-level observations with molecular mechanisms to comprehensively understand the exposome. We strategically select complementary models to address questions in their most relevant biological context.

1. Chemical Chaperones in Protein Homeostasis

We investigate how endogenous metabolites function as chemical chaperones through:

  • Establishing mechanistic insights into how cellular small molecules assist protein folding and stabilization

  • Characterizing the cooperative and counteractive effects of metabolite networks on protein structure using quantitative proteomics

  • Mapping proteome-wide conformational changes using Limited-proteolysis coupled to mass spectrometry (LiP-MS) proteomics.

2. Protein Misfolding in Aging and Stress Response

We integrate advanced biophysical approaches to explore how aging and environmental stressors influence protein misfolding through:

  • Developing genetic tools for compartment-specific metabolic manipulation combined with structural proteomics to map stress-induced conformational changes

  • Characterizing the dynamics of biomolecular condensate formation under biotic and abiotic stressors using advanced imaging techniques and spectroscopy

  • Investigating protein quality control systems during aging using quantitative mass spectrometry-based proteomics and high-resolution microscopy

3. Integrative Analysis of Metabolite-Protein Conformational Landscapes

We develop data-driven platform approaches to understand and leverage complex metabolite-protein interactions through:

  • Establishing automated screening platforms for systematic analysis of protein-metabolite interactions

  • Combining multi-modal detection methods to track conformational changes and protein stability

  • Developing quantitative frameworks that can be adapted for therapeutic discovery pipelines