Welcome to Gao Lab

Innate immunity serves as first line of host defense. The mammalian innate immune system mainly employs pattern recognition receptors (PRRs) to detect conserved molecules from pathogens. Pathogen nucleic acids which possess distinct features with host nucleic acids, are recognized by host innate immune receptors, including TLRs on the endosomal membrane and cytosolic sensing pathways. Recently the breakthrough in cytosolic DNA sensing pathways drew a lot of attention. Cytosolic DNA from pathogens is sensed by the cGAS protein, which synthesize cyclic di-nucleotide cGAMP. cGAMP further activates STING on the ER membrane and initiate IFN response, which limits pathogen propagation. cGAS is sensor for various pathogens which use DNA as genetic materials, including DNA viruses, retroviruses (HIV), bacteria and parasites. cGAS STING pathway is Associated with cancer and neural degerative disease.

What's more, dysregulation of nucleic acid metabolism causes innate immune overactivation. Dnase (Trex1 or Dnase-II) deficient mice or patients have self-DNA accumulation and manifest life-threatening autoimmunity. Genetic ablation of cGAS rescue mice from autoimmune phenotypes, indicating the pivotal role of cGAS in contribution in autoimmunity.

Aicardi-Goutières syndrome and the type I interferonopathies Yanick J. Crow & Nicolas Manel. Nat Rev Immunol 2015

Nucleic acid metabolism also involves in antiviral immunity. DBR1 is RNA debranching enzyme, which is necessary for RNA lariats (by product of RNA splicing) degradation. Human deficiency of DBR1 has been shown to cause hindbrain encephalitis.

Here we are trying to idenfy more enzymes which both participate in nucleic acid metabolism and innate immunity. By using sing cell sequencing, the state-of-the-art CRSIPR technology and traditional molecular biology methods, we are interested in dissecting the mechanism of regulation of innate immunity by nucleic acid metabolism.