The research in my lab focuses on elucidating the structural basis of innate immune responses towards microbial nucleic acids. The cGAS/STING pathway plays a central role in innate immunity toward bacterial and viral DNA. cGAS is activated by dsDNA and catalyzes the synthesis of a cyclic dinucleotide cGAMP, which binds to the adaptor STING that mediates the recruitment and activation of protein kinase TBK1 and transcription factor IRF-3. Activated IRF-3 translocates to the nucleus and induces the expression of type I interferons (IFN), an important family of antiviral cytokine. To elucidate the mechanism of cGAS activation, we determined the structures of cGAS in isolation and in complex with DNA. The cGAS/DNA complex structure reveals that cGAS interacts with DNA through two binding sites. Enzyme assays and IFN-? reporter assays of cGAS mutants demonstrate that interactions at both DNA binding sites are essential for cGAS activation. To investigate how cGAMP activates STING, we determined the structures of STING in isolation and in complex with cGAMP. These structures reveal that STING forms a V-shaped dimer and binds cGAMP at the dimer interface. We have also determined the structures of TBK1 in complex with two inhibitors, which show that TBK1 exhibits an I?B kinase fold with distinct domain arrangement. To elucidate the mechanism of IRF-3 recruitment by STING, we determined the structure of a phosphorylated STING peptide bound to IRF-3. To understand how phosphorylation activates IRF-3, we solved the structure of an IRF-3 phosphomimetic mutant bound to CBP, which reveals how phosphorylation induces the dimerization and activation of IRF-3.

education and training
selected publications
Academic Articles59
  • Yang, K. S., Ma, X. R., Ma, Y., Alugubelli, Y. R., Scott, D. A., Vatansever, E. C., ... Liu, W. R. (2021). A Quick Route to Multiple Highly Potent SARS-CoV-2 Main Protease Inhibitors*.. ChemMedChem. 16(6), 942-948.
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  • Liu, J., Huang, Y., Kong, L., Yu, X., Feng, B., Liu, D., ... He, P. (2020). The malectin-like receptor-like kinase LETUM1 modulates NLR protein SUMM2 activation via MEKK2 scaffolding.. Nat Plants. 6(9), 1106-1115.
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  • Cho, J., Zhao, B., Shi, J., Savage, N., Shen, Q., Byrnes, J., ... Li, P. (2020). Molecular recognition of a host protein by NS1 of pandemic and seasonal influenza A viruses.. Proc Natl Acad Sci U S A. (12), 6550-6558.
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  • Hoffpauir, C. T., Bell, S. L., West, K. O., Jing, T., Wagner, A. R., Torres-Odio, S., ... Watson, R. O. (2020). TRIM14 Is a Key Regulator of the Type I IFN Response during Mycobacterium tuberculosis Infection.. J Immunol. (1), 153-167.
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  • Jing, T., Zhao, B., Xu, P., Gao, X., Chi, L., Han, H., Sankaran, B., & Li, P. (2020). The Structural Basis of IRF-3 Activation upon Phosphorylation.. J Immunol. (7), 1886-1896.
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Conference Papers1
  • Shen, Q., Shi, J., Li, P., Hwang, W., & Cho, J. (2018). Tight Binding through Structural Disorder: Mechanism and Application. Biophysical Journal. 114(3), 427a-428a.
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Repository Documents / Preprints2
  • Weindel, C. G., Zhao, X., Martinez, E., Bell, S. L., Vail, K. J., Coleman, A. K., ... Watson, R. O. (2021). Mitochondrial dysfunction promotes alternative gasdermin D-mediated inflammatory cell death and susceptibility to infection.
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  • Hoffpauir, C. T., Bell, S. L., West, K. O., Jing, T., Torres-Odio, S., Cox, J. S., ... Watson, R. O. (2019). TRIM14 is a key regulator of the type I interferon response during Mycobacterium tuberculosis infection.
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chaired theses and dissertations
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mailing address
Texas A&M University; Biochemistry & Biophysics; 2128 TAMU
College Station, TX 77843-2128