We utilize a mouse model with a variety of knock-out and knock-in mouse lines to investigate viral pathogenesis, and also employ unbiased screening using CRISPR knock-out (CRISPRko) and CRISPR activation (CRISPRa) techniques to discover novel anti-viral or pro-viral cellular genes.

Discovery of novel cellular genes and pathways modulating virus infection

We employ unbiased screening platforms including CRISPR screening (e.g., CRISPR knock-out (CRISPRko) and CRISPR activation (CRISPRa) techniques) to discover novel anti-viral or pro-viral cellular genes. We focus on Noroviruses and SARS-CoV-2 to identify the novel cellular factors. We recently employed the CRISPRa screening technique and identified LRRC15 as a novel inhibitory receptor for SARS-CoV-2 (Song et al., Plos Biol, 2022). 

Pathogenesis and cell tropism of murine norovirus in a mouse model

Noroviruses (NoVs) are single-stranded RNA virus, the leading cause of virally induced gastric enteritis in global. We study murine norovirus (MNoV) as a model pathogen to understand cellular tropism, and the contribution of innate and adaptive immunity to control norovirus infection in the intestine of mice. We recently found the cellular tropism of norovirus for persistent infection to be rare intestinal epithelial cells, called tuft cells. We are investigating what features of tuft cells allow persistence and how MNoV evade cell intrinsic and extrinsic immune responses.

Study of innate & adaptive immune controls of viral infection and immune evasion by viruses

We identified type III interferon (IFN-λ) as a cellular determinant controlling tuft cell tropism of murine norovirus, and also found that the virus counteract the control of IFN-λ by secreted viral protein, NS1. We are presently investigating the molecular mechanism of NS1-mediated IFN-λ immune evasion and evaluating NS1 as a novel vaccine target. Identifying the critical component of immune control of viral pathogenesis in the host organism and the counteracting mechanism of immune evasion is the key focus of our research program.

We believe that better understanding viral replication and pathogenesis not only provides an insight into new therapeutics or vaccines, but also often reveals new concepts of biological processes.