Honors & Awards


  • Centennial Teaching Award, Stanford University - Office of the Vice Provost for Teaching and Learning (2016)

Education & Certifications


  • B.S., Ouachita Baptist University, Arkadelphia, Arkansas, Majors in Professional Chemistry and Physics, Minors in Mathematics and Biology (2014)

Stanford Advisors


Lab Affiliations


All Publications


  • The IFN-λ-IFN-λR1-IL-10Rβ Complex Reveals Structural Features Underlying Type III IFN Functional Plasticity. Immunity Mendoza, J. L., Schneider, W. M., Hoffmann, H. H., Vercauteren, K., Jude, K. M., Xiong, A., Moraga, I., Horton, T. M., Glenn, J. S., de Jong, Y. P., Rice, C. M., Garcia, K. C. 2017; 46 (3): 379–92

    Abstract

    Type III interferons (IFN-λs) signal through a heterodimeric receptor complex composed of the IFN-λR1 subunit, specific for IFN-λs, and interleukin-10Rβ (IL-10Rβ), which is shared by multiple cytokines in the IL-10 superfamily. Low affinity of IL-10Rβ for cytokines has impeded efforts aimed at crystallizing cytokine-receptor complexes. We used yeast surface display to engineer a higher-affinity IFN-λ variant, H11, which enabled crystallization of the ternary complex. The structure revealed that IL-10Rβ uses a network of tyrosine residues as hydrophobic anchor points to engage IL-10 family cytokines that present complementary hydrophobic binding patches, explaining its role as both a cross-reactive but cytokine-specific receptor. H11 elicited increased anti-proliferative and antiviral activities in vitro and in vivo. In contrast, engineered higher-affinity type I IFNs did not increase antiviral potency over wild-type type I IFNs. Our findings provide insight into cytokine recognition by the IL-10R family and highlight the plasticity of type III interferon signaling and its therapeutic potential.

    View details for DOI 10.1016/j.immuni.2017.02.017

    View details for PubMedID 28329704

  • Modification by covalent reaction or oxidation of cysteine residues in the tandem-SH2 domains of ZAP-70 and Syk can block phosphopeptide binding BIOCHEMICAL JOURNAL Visperas, P. R., Winger, J. A., Horton, T. M., Shah, N. H., Aum, D. J., Tao, A., Barros, T., Yan, Q., Wilson, C. G., Arkin, M. R., Weiss, A., Kuriyan, J. 2015; 465: 149-161

    Abstract

    Zeta-chain associated protein of 70 kDa (ZAP-70) and spleen tyrosine kinase (Syk) are non-receptor tyrosine kinases that are essential for T-cell and B-cell antigen receptor signalling respectively. They are recruited, via their tandem-SH2 (Src-homology domain 2) domains, to doubly phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) on invariant chains of immune antigen receptors. Because of their critical roles in immune signalling, ZAP-70 and Syk are targets for the development of drugs for autoimmune diseases. We show that three thiol-reactive small molecules can prevent the tandem-SH2 domains of ZAP-70 and Syk from binding to phosphorylated ITAMs. We identify a specific cysteine residue in the phosphotyrosine-binding pocket of each protein (Cys39 in ZAP-70, Cys206 in Syk) that is necessary for inhibition by two of these compounds. We also find that ITAM binding to ZAP-70 and Syk is sensitive to the presence of H2O2 and these two cysteine residues are also necessary for inhibition by H2O2. Our findings suggest a mechanism by which the reactive oxygen species generated during responses to antigen could attenuate signalling through these kinases and may also inform the development of ZAP-70 and Syk inhibitors that bind covalently to their SH2 domains.

    View details for DOI 10.1042/BJ20140793

    View details for Web of Science ID 000351685300012

    View details for PubMedID 25287889