Your research spans advanced EPR spectroscopic techniques (CW EPR, DEER, ENDOR, EDNMR) to investigate disordered proteins and metalloproteins. What inspired you to focus on this interdisciplinary area, and how has your vision for biomolecular EPR evolved since you started your lab?
My research is driven by the unique versatility of advanced Electron Paramagnetic Resonance (EPR) spectroscopy, which naturally bridges chemistry, physics, and biology. Despite major advances in AI-based structure prediction tools such as AlphaFold, understanding the structure and dynamics of disordered proteins remains highly challenging, and EPR is uniquely suited to probe such systems. Metalloproteins, which often contain EPR-active paramagnetic centers, play central roles in catalysis and electron transfer, making the characterization of their electronic structures in resting states and reactive intermediates essential. Over time, my vision has expanded beyond purified systems toward more complex biological environments, including native and in vivo contexts. Advances in EPR methodology and instrumentation have also broadened its applicability to other frontiers such as materials chemistry and nanobiotechnology.
Disordered proteins and reactive metalloprotein intermediates pose major challenges in molecular biophysics. What is the most critical unanswered question in this space today, and how is your group addressing it?
For disordered proteins, a central unanswered question is how transient local interactions and conformational dynamics translate into long-range functional regulation within the crowded cellular environment. In metalloproteins, the challenge lies in trapping and accurately characterizing highly diverse reactive intermediates, whose electronic structures are sensitive to subtle changes in coordination environments. My group addresses these challenges using advanced EPR methodologies integrated with computational tools and complementary spectroscopic techniques such as NMR, FRET, and rapid freeze-quench methods to capture functionally relevant intermediates.
How do you see the future of biomolecular spectroscopy evolving, and which emerging technologies excite you most?
Biomolecular spectroscopy is evolving toward hybrid, integrative approaches that combine EPR with Cryo-EM, NMR, mass spectrometry, and AI-driven modeling. Long-range distance constraints from EPR/DEER (1.5–10 nm), particularly for flexible disordered regions, will be critical for validating structural reconstructions from Cryo-EM. New experimental protocols are also expected to bridge the gap between solution-based and in-cell spectroscopy. I am particularly excited to integrate Cryo-EM and AI-based computational modeling with EPR to study structure and function in their full biological context.
Which interdisciplinary collaborations could significantly expand the impact of your research?
Major breakthroughs often emerge from interdisciplinary research. Collaborations with computational scientists specializing in AI, machine learning, and molecular dynamics can enable accurate prediction of functional conformational ensembles. Partnerships with materials scientists and nanotechnologists can further extend our work toward designing robust, enzyme-mimicking catalysts with industrial relevance.
What guidance would you offer to young scientists entering this field?
Addressing such complex problems requires a strong interdisciplinary foundation that integrates spectroscopy, biochemistry, and computational tools. EPR should not be treated as an endpoint, but interpreted alongside complementary spectroscopic methods, Cryo-EM, and computational analysis to achieve a comprehensive molecular understanding. For young scientists entering this field, I encourage a problem-driven approach focused on real-world challenges, including uncovering molecular mechanisms of disease and designing efficient catalysts to address environmental problems.
