Our research focuses on developing computational algorithms and conducting big data mining from high-throughput data to understand the role of gene regulation and cellular cross-talks in cell state transition and fate determination. We have developed a series of algorithms and web resources for single-cell transcriptomics, epigenomic, CRISPR-screens and spatial transcriptomic data analysis and re-use. Through integrating multi-omics single-cell and spatial datasets, we try to decipher the transcriptional and epigenetic regulatory mechanisms underlying tumor progression, anti-tumor immunity, cellular and organ level differentiation.
Computational methods for single-cell and spatial multi-omics
We have developed computational methods(MAESTRO) for integrative analysis of scRNA-seq and scATAC-seq data. We also created a scRNA-seq database for comprehensive visualization of the gene expression and cell-type composition in tumor microenvironment(TISCH). Now we are working on multiple challenging questions in single-cell filed including automatic cell-type annotation, predicting and unraveling the regulation networks based on scATAC-seq data, improving the resolution of spatial transcriptomics by integrating with scRNA-seq, and inferring the cellular cross-talks based on spatial transcriptomics data.
Mechanism in generating and remodeling immunosuppressive tumor microenvironment
Cancer arises through evasion of immune killing. We are working on utilizing scRNA-seq, scATAC-seq, scCRISPR screens, and spatial transcriptomics to deciphering the cellular heterogeneity and dynamics in the tumor microenvironment. We hope to discover intra- or inter-cellular mechanisms in generating immunosuppressive tumor microenvironment and develop novel strategies in remodeling the TME to cure cancer. We are now collaborating with immunologists and oncologists to studying the mechanism of carcinogenesis, immune and drug resistance in the oral, lung, and cervical cancer.
Genetics and epigenetics regulation of cell-fate decision
We aimed to investigate the gene regulation mechanisms in cell state transition and fate control, which could be used to improve the efficiency in rewiring cell fate. We have been studying the epigenetic inheritance and reprogramming during mammalian embryo development and its effect on embryogenesis and cell fate determination. We have revealed the dynamics of H3K4me3, H3K27me3, and H3K9me3 during mouse early embryo development, and demonstrated the function of broad H3K4me3 and lineage-specific H3K9me3 in cell-type differentiation (Nature 2016, Nat Cell Biol 2018). We have also identified key epigenetic regulators in somatic nuclear-transferred embryo development (Cell Discov 2016, Cell Stem Cell 2018).