Current research interests include the following three areas:
Visualization of Chromatin and Epigenetic Dynamics
Gene expression is regulated by epigenetic modifications in many cellular processes. Epigenetic modifications, including histone modifications, DNA methylation, and RNA methylation, at different residues can recruit differential sets of chromatin remodeling complexes to silence or activate specific gene expressions. Fluorescent Resonance Energy Transfer (FRET) biosensors based on fluorescent proteins (FPs) have been well established to monitor dynamic molecular events in single cells. We have successfully developed a new histone H3K9me3 FRET biosensor and a new histone H3S10ph FRET biosensor, and visualize the dynamic coordination between histone modifications in regulation chromatin structures and cell cycles in single living cells.
FRET Biosensor Development
We integrate random mutagenesis, phage/yeast/mammalian display, and FACS to systematically develop novel FRET biosensors with optimized specificity and sensitivity. The systematic approach developed can be readily extended to the development/optimization of, in principle, any FRET biosensor for the detection of chromatin structure and epigenetics. We have successfully developed a new hybrid FRET biosensor by using directed evolution technology and sequence-function analysis to engineer a monoboby into an efficient R-PE binder, PEbody, to directly capture R-PE.
4D Imaging Platform of Epigenetics
Visualize the epigenetic dynamics at specific critical genes identified from RNA-seq, and verify the locus-specific epigenetics in disease models, e.g. cancer, progeria, immune disease.