Honors & Awards

  • Research Supplement to Promote Diversity in Health-Related Research, NIH NIAID (2022 - 2025)
  • Microbiology and Immunology Departmental T32 Fellowship, Stanford University (2021)
  • Women’s Council Recognition Award, UNLV (2019)
  • Outstanding Graduate Student Teacher Award, UNLV (2019)
  • Summer Doctoral Research Fellowship, UNLV (2018 - 2020)
  • Space Grant Consortium Graduate Research Fellowship, NASA (2016)
  • IDeA Network of Biomedical Research Excellence Scholarship, NV INBRE (2012)

Stanford Advisors

All Publications

  • Transcriptional profiling links unique human macrophage phenotypes to the growth of intracellular Salmonella enterica serovar Typhi. Scientific reports Schade, R., Butler, D. S., McKenna, J. A., Di Luccia, B., Shokoohi, V., Hamblin, M., Pham, T. H., Monack, D. M. 2024; 14 (1): 12811


    Macrophages provide a crucial environment for Salmonella enterica serovar Typhi (S. Typhi) to multiply during typhoid fever, yet our understanding of how human macrophages and S. Typhi interact remains limited. In this study, we delve into the dynamics of S. Typhi replication within human macrophages and the resulting heterogeneous transcriptomic responses of macrophages during infection. Our study reveals key factors that influence macrophage diversity, uncovering distinct immune and metabolic pathways associated with different stages of S. Typhi intracellular replication in macrophages. Of note, we found that macrophages harboring replicating S. Typhi are skewed towards an M1 pro-inflammatory state, whereas macrophages containing non-replicating S. Typhi exhibit neither a distinct M1 pro-inflammatory nor M2 anti-inflammatory state. Additionally, macrophages with replicating S. Typhi were characterized by the increased expression of genes associated with STAT3 phosphorylation and the activation of the STAT3 transcription factor. Our results shed light on transcriptomic pathways involved in the susceptibility of human macrophages to intracellular S. Typhi replication, thereby providing crucial insight into host phenotypes that restrict and support S. Typhi infection.

    View details for DOI 10.1038/s41598-024-63588-6

    View details for PubMedID 38834738

    View details for PubMedCentralID 6376096

  • Localized modulation of DNA supercoiling, triggered by the Shigella anti-silencer VirB, is sufficient to relieve H-NS-mediated silencing Nucleic Acids Research Picker, M. P., Karney, M. M., Gerson, T. M., Karabachev, A. D., Duhart, J. C., McKenna, J. A., Wing, H. J. 2023

    View details for DOI 10.1093/nar/gkad088

  • The AraC/XylS Protein MxiE and Its Coregulator IpgC Control a Negative Feedback Loop in the Transcriptional Cascade That Regulates Type III Secretion in Shigella flexneri. Journal of bacteriology McKenna, J. A., Karney, M. M., Chan, D. K., Weatherspoon-Griffin, N., Becerra Larios, B., Pilonieta, M. C., Munson, G. P., Wing, H. J. 2022: e0013722


    Members of the AraC family of transcriptional regulators (AFTRs) control the expression of many genes important to cellular processes, including virulence. In Shigella species, the type III secretion system (T3SS), a key determinant for host cell invasion, is regulated by the three-tiered VirF/VirB/MxiE transcriptional cascade. Both VirF and MxiE belong to the AFTRs and are characterized as positive transcriptional regulators. Here, we identify a novel regulatory activity for MxiE and its coregulator IpgC, which manifests as a negative feedback loop in the VirF/VirB/MxiE transcriptional cascade. Our findings show that MxiE and IpgC downregulate the virB promoter and, hence, VirB protein production, thus decreasing VirB-dependent promoter activity at ospD1, one of the nearly 50 VirB-dependent genes. At the virB promoter, regions required for negative MxiE- and IpgC-dependent regulation were mapped and found to be coincident with regions required for positive VirF-dependent regulation. In tandem, negative MxiE- and IpgC-dependent regulation of the virB promoter only occurred in the presence of VirF, suggesting that MxiE and IpgC can function to counter VirF activation of the virB promoter. Lastly, MxiE and IpgC do not downregulate another VirF-activated promoter, icsA, demonstrating that this negative feedback loop targets the virB promoter. Our study provides insight into a mechanism that may reprogram Shigella virulence gene expression following type III secretion and provides the impetus to examine if MxiE and IpgC homologs in other important bacterial pathogens, such as Burkholderia pseudomallei and Salmonella enterica serovars Typhimurium and Typhi, coordinate similar negative feedback loops. IMPORTANCE The large AraC family of transcriptional regulators (AFTRs) control virulence gene expression in many bacterial pathogens. In Shigella species, the AraC/XylS protein MxiE and its coregulator IpgC positively regulate the expression of type III secretion system genes within the three-tiered VirF/VirB/MxiE transcriptional cascade. Our findings suggest a negative feedback loop in the VirF/VirB/MxiE cascade, in which MxiE and IpgC counter VirF-dependent activation of the virB promoter, thus making this the first characterization of negative MxiE- and IpgC-dependent regulation. Our study provides insight into a mechanism that likely reprograms Shigella virulence gene expression following type III secretion, which has implications for other important bacterial pathogens with functional homologs of MxiE and IpgC.

    View details for DOI 10.1128/jb.00137-22

    View details for PubMedID 35703565

  • The Antiactivator of Type III Secretion, OspD1, Is Transcriptionally Regulated by VirB and H-NS from Remote Sequences in Shigella flexneri JOURNAL OF BACTERIOLOGY McKenna, J. A., Wing, H. J. 2020; 202 (10)


    Shigella species, the causal agents of bacillary dysentery, use a type III secretion system (T3SS) to inject two waves of virulence proteins, known as effectors, into the colonic epithelium to subvert host cell machinery. Prior to host cell contact and secretion of the first wave of T3SS effectors, OspD1, an effector and antiactivator protein, prevents premature production of the second wave of effectors. Despite this important role, regulation of the ospD1 gene is not well understood. While ospD1 belongs to the large regulon of VirB, a transcriptional antisilencing protein that counters silencing mediated by the histone-like nucleoid structuring protein H-NS, it remains unclear if VirB directly or indirectly regulates ospD1 Additionally, it is not known if ospD1 is regulated by H-NS. Here, we identify the primary ospD1 transcription start site (+1) and show that the ospD1 promoter is remotely regulated by both VirB and H-NS. Our findings demonstrate that VirB regulation of ospD1 requires at least one of the two newly identified VirB regulatory sites, centered at -978 and -1270 relative to the ospD1 +1. Intriguingly, one of these sites lies on a 193-bp sequence found in three conserved locations on the large virulence plasmids of Shigella The region required for H-NS-dependent silencing of ospD1 lies between -1120 and -820 relative to the ospD1 +1. Thus, our study provides further evidence that cis-acting regulatory sequences for transcriptional antisilencers and silencers, such as VirB and H-NS, can lie far upstream of the canonical bacterial promoter region (i.e., -250 to +1).IMPORTANCE Transcriptional silencing and antisilencing mechanisms regulate virulence gene expression in many important bacterial pathogens. In Shigella species, plasmid-borne virulence genes, such as those encoding the type III secretion system (T3SS), are silenced by the histone-like nucleoid structuring protein H-NS and antisilenced by VirB. Previous work at the plasmid-borne icsP locus revealed that VirB binds to a remotely located cis-acting regulatory site to relieve transcriptional silencing mediated by H-NS. Here, we characterize a second example of remote VirB antisilencing at ospD1, which encodes a T3SS antiactivator and effector. Our study highlights that remote transcriptional silencing and antisilencing occur more frequently in Shigella than previously thought, and it raises the possibility that long-range transcriptional regulation in bacteria is commonplace.

    View details for DOI 10.1128/JB.00072-20

    View details for Web of Science ID 000532698800003

    View details for PubMedID 32123035

    View details for PubMedCentralID PMC7186461

  • Investigating the DNA-Binding Site for VirB, a Key Transcriptional Regulator of Shigella Virulence Genes, Using an In Vivo Binding Tool GENES Karney, M. A., McKenna, J. A., Weatherspoon-Griffin, N., Karabachev, A. D., Millar, M. E., Potocek, E. A., Wing, H. J. 2019; 10 (2)


    The transcriptional anti-silencing and DNA-binding protein, VirB, is essential for the virulence of Shigella species and, yet, sequences required for VirB-DNA binding are poorly understood. While a 7-8 bp VirB-binding site has been proposed, it was derived from studies at a single VirB-dependent promoter, icsB. Our previous in vivo studies at a different VirB-dependent promoter, icsP, found that the proposed VirB-binding site was insufficient for regulation. Instead, the required site was found to be organized as a near-perfect inverted repeat separated by a single nucleotide spacer. Thus, the proposed 7-8 bp VirB-binding site needed to be re-evaluated. Here, we engineer and validate a molecular tool to capture protein-DNA binding interactions in vivo. Our data show that a sequence organized as a near-perfect inverted repeat is required for VirB-DNA binding interactions in vivo at both the icsB and icsP promoters. Furthermore, the previously proposed VirB-binding site and multiple sites found as a result of its description (i.e., sites located at the virB, virF, spa15, and virA promoters) are not sufficient for VirB to bind in vivo using this tool. The implications of these findings are discussed.

    View details for DOI 10.3390/genes10020149

    View details for Web of Science ID 000460742800078

    View details for PubMedID 30781432

    View details for PubMedCentralID PMC6410309

  • Insights into transcriptional silencing and anti-silencing in Shigella flexneri: a detailed molecular analysis of the icsP virulence locus MOLECULAR MICROBIOLOGY Weatherspoon-Griffin, N., Picker, M. A., Pew, K. L., Park, H. S., Ginete, D. R., Karney, M. A., Usufzy, P., Castellanos, M. I., Duhart, J., Harrison, D. J., Socea, J. N., Karabachev, A. D., Hensley, C. T., Howerton, A. J., Ojeda-Daulo, R., Immak, J. A., Wing, H. J. 2018; 108 (5): 505–18


    Transcriptional silencing and anti-silencing mechanisms modulate bacterial physiology and virulence in many human pathogens. In Shigella species, many virulence plasmid genes are silenced by the histone-like nucleoid structuring protein H-NS and anti-silenced by the virulence gene regulator VirB. Despite the key role that these regulatory proteins play in Shigella virulence, their mechanisms of transcriptional control remain poorly understood. Here, we characterize the regulatory elements and their relative spacing requirements needed for the transcriptional silencing and anti-silencing of icsP, a locus that requires remotely located regulatory elements for both types of transcriptional control. Our findings highlight the flexibility of the regulatory elements' positions with respect to each other, and yet, a molecular roadblock docked between the VirB binding site and the upstream H-NS binding region abolishes transcriptional anti-silencing by VirB, providing insight into transcriptional anti-silencing. Our study also raises the need to re-evaluate the currently proposed VirB binding site. Models of transcriptional silencing and anti-silencing at this genetic locus are presented, and the implications for understanding these regulatory mechanisms in bacteria are discussed.

    View details for DOI 10.1111/mmi.13932

    View details for Web of Science ID 000434156400005

    View details for PubMedID 29453862

    View details for PubMedCentralID PMC6311345

  • Characterization of the ospZ Promoter in Shigella flexneri and Its Regulation by VirB and H-NS JOURNAL OF BACTERIOLOGY Basta, D. W., Pew, K. L., Immak, J. A., Park, H. S., Picker, M. A., Wigley, A. F., Hensley, C. T., Pearson, J. S., Hartland, E. L., Wing, H. J. 2013; 195 (11): 2562–72


    OspZ is an effector protein of the type III secretion system in Shigella spp. that downregulates the human inflammatory response during bacterial infection. The ospZ gene is located on the large virulence plasmid of Shigella. Many genes on this plasmid are transcriptionally repressed by the nucleoid structuring protein H-NS and derepressed by VirB, a DNA-binding protein that displays homology to the plasmid partitioning proteins ParB and SopB. In this study, we characterized the ospZ promoter and investigated its regulation by H-NS and VirB in Shigella flexneri. We show that H-NS represses and VirB partially derepresses the ospZ promoter. H-NS-mediated repression requires sequences located between -731 and -412 relative to the beginning of the ospZ gene. Notably, the VirB-dependent derepression of ospZ requires the same VirB binding sites as are required for the VirB-dependent derepression of the divergent icsP gene. These sites are centered 425 bp upstream of the ospZ gene but over 1 kb upstream of the icsP transcription start site. Although these VirB binding sites lie closer to ospZ than icsP, the VirB-dependent increase in ospZ promoter activity is lower than that observed at the icsP promoter. This indicates that the proximity of VirB binding sites to Shigella promoters does not necessarily correlate with the level of VirB-dependent derepression. These findings have implications for virulence gene regulation in Shigella and other pathogens that control gene expression using mechanisms of transcriptional repression and derepression.

    View details for DOI 10.1128/JB.00212-13

    View details for Web of Science ID 000318811300013

    View details for PubMedID 23543709

    View details for PubMedCentralID PMC3676053