The innate immune system uses pattern recognition receptors (PRRs) in different cellular compartments to discriminate among microbial components that mark invading pathogens. Cytosolic nucleic acid, such as viral RNA and DNA, and even host DNA leaked from the nucleus and the mitochondria, triggers innate immune responses by producing type I interferons and other cytokines and chemokines. The major PRRs for cytosolic RNA and DNA are RIG-I and cGAS, respectively. Using a proteomics approach, our laboratory mapped the protein interaction networks of RIG-I and cGAS, which consist of many novel binding factors. Further study found several binding proteins were required for the activation of RIG-I or cGAS. The current research goal of our team is to elucidate how these factors regulate RIG-I or/and cGAS signaling pathways. We adopt various omics, molecular approaches, and genetics to investigate their roles in nucleic acid-mediated innate immunity. We also extend these studies to elucidate the role of innate immunity in autoimmune diseases and cancers using several mouse models established in the laboratory.
Another interest in our laboratory is to study the interactions between influenza A virus and host, and how these interactions modulate host defense and viral infection. We have established comparative influenza-host protein interaction networks. From the pilot screening of a small pool of our network, we found several novel anti-flu host factors. We will continue the screening and investigate the role of new host factors in influenza pathogenesis.
- Nucleic acid-mediated innate immune signaling pathways
- Role of innate immunity in autoimmune diseases and tumorigenesis
- Influenza-host interactions