Ensemble studies have contributed tremendously to comprehending biological reactions. However, these studies characterize the average molecular population, and have limited ability in detecting intermediate states or distinguishing heterogeneities. Over the past few decades, single-molecule techniques, including fluorescence resonance energy transfer (FRET), magnetic tweezers (MT) and optical tweezers (OT), have proven to be exceedingly powerful in addressing this knowledge gap. By studying one molecule at a time, these approaches have enabled significant advancement in the understanding of a wide variety of biomolecular systems, especially those involving DNA and associated proteins. Using these single‐molecule techniques, our research interests focus on understanding mechanisms and functions of molecular motors in the process of DNA replication, repair, recombination, and editingsuch as helicase, polymerase and nuclease, and developing technological innovations to meet the challenges in the pursuits. In addition, we are working on understanding structures and functions of membraneless organelles and RNA-binding proteins. Our lab currently covers four major research fields:


  • Molecular mechanisms of CRISPR-Cas proteins We use a series of single-molecule techniques to understand the detailed molecular mechanisms of CRISPR-Cas proteins, such as spCas9 and saCas9, in order to increase their fidelity, minimize off-target cleavage, and ensure their efficient applications in medicine and biology.
  • Homologous recombination-directed DSB repair DNA repair and recombination are essential for maintaining genome integrity. We combine biophysical manipulation techniques with fluorescence imaging to control, visualize and dissect key steps in the recombination reaction mediated by many molecular proteins down to the single molecule.
  • Replication restart pathways after collision with obstacles To ensure accurate DNA replication, a replisome must effectively overcome numerous obstacles on its DNA substrate. We empoly single-molecule techniques to reveal pathways that cells have evolved to possess in order to avoid replication failure from fork barriers, such as DNA damage and DNA -bound complexes.
  • RNA structure and piRNA biogenesis The maturation and function of piRNAs are highly dependent on the coordinated action of several RNA-binding proteins. Using ensemble and single-molecule methods, we aim to understand the mechanisms and funcitons of essential RNA-binding proteins, such as MOV10L1, in piRNA biogenesis.