- BS, Chemical Physics, University of Science and Technology of China, China
- PhD, Molecular Biology, Case Western Reserve University
- Postdoc, Molecular Biology, Yale University, New Haven, CT
Biochemistry, Bioinformatics and Genomics, Biotechnology, Cancer Biology, Computational Biology, Development, Epigenetics, Experimental Pathology, Genetics, Molecular and Cellular Physiology, Molecular Biology, Molecular Physiology and Biological Physics, Neuroscience, Stem Cells & Regeneration, Structural Biology, Translational Science
Gene regulation in cancer, RNA processing; Epigenetic modification; Stem cell and development
Targeted therapy: by serendipity, we identified a novel oncogene, and found that multiple cancers are addicted to its activity. This oncogene addiction is evidenced in glioblastoma, pediatric sarcoma, and others. About half of the lab members are working on figuring out the mechanisms of this oncogene, how is it activated, how does it work, and developing small molecule inhibitors to target it. Various animal models are also constructed to study its fundamental biology as well as testing the efficacy and safety of small molecule compounds.
Chimeric RNA and system biology: One of the central paradigms is that genes are located in isolated zones, minding their own business (making their own RNAs and proteins) and don’t usually cross talk with each other, except in pathological situations. For example, one of the hallmarks in cancer is DNA rearrangement, which results in the fusion of two separate genes. These gene fusion products often play critical roles in cancer development. Traditionally, they are thought to be the sole product of DNA rearrangement and therefore unique to cancer. This belief forms the basis for many cancer diagnostic and therapeutic approaches. Recently, we discovered two mechanisms that could generate fusion products without DNA rearrangement. One of the process is called “RNA trans-splicing”, whereby two separate RNAs can be spliced together and generate a fusion RNA, which then can be translated into a fusion protein. The other process involves two neighboring genes transcribing in the same direction, “cis-Splicing of Adjacent Genes (cis-SAGe). Our work on RNA trans-splicing and intergenic cis-splicing have posed a challenge to the traditional views and helped open a new paradigm for intergenic splicing processes that generate gene products in normal physiological conditions: even in the absence of physically “touching” each other, genes do send messages (messenger RNA) that can be mingled together. These mechanisms may also be ways to expand out functional genome, and explaining the enigma that human and mouse, even worm share a similar number of genes. Our long-term goals are to understand the scope of these phenomena, the physiological functions of these “intergenic splicing” process and their implications in both normal development and in cancer. We are using a wide range of approaches ranging from state-of-art bioinformatic pipeline to modified CRISPR/CAS9 systems.
Immune therapy: The new process of RNA splicing offers a new repertoire for potential biomarkers and therapeutic targets. We found such chimeric RNA specifically expressed in various cancer types. A subset of them encode novel proteins or peptides. They represent ideal neo-antigens as cancer vaccine. Some are also membrane proteins which enable the CAR-T therapy or antibody conjugated drug development.