Honors & Awards


  • Dean's Postdoctoral Fellowship, Stanford School of Medicine (2016)
  • Postdoctoral Fellowship Award, Department of Microbiology and Immunology, Stanford School of Medicine, NIH Training Grant (2015)
  • Nominee, Weintraub Graduate Award, Fred Hutchinson Cancer Research Center (2014)
  • Honorable Mention, NSF Graduate Research Fellowship (2010)
  • Alumni Scholarship for Emerging Leaders, University of California, Berkeley (2004)
  • Dean's Honor List, University of California, Berkeley (2003)

Professional Education


  • Doctor of Philosophy, Harvard University (2014)
  • Bachelor of Arts, University of California Berkeley (2006)

Stanford Advisors


All Publications


  • Cutting Edge: Inflammasome Activation in Primary Human Macrophages Is Dependent on Flagellin JOURNAL OF IMMUNOLOGY Kortmann, J., Brubaker, S. W., Monack, D. M. 2015; 195 (3): 815-819

    Abstract

    Murine NLR family, apoptosis inhibitory protein (Naip)1, Naip2, and Naip5/6 are host sensors that detect the cytosolic presence of needle and rod proteins from bacterial type III secretion systems and flagellin, respectively. Previous studies using human-derived macrophage-like cell lines indicate that human macrophages sense the cytosolic needle protein, but not bacterial flagellin. In this study, we show that primary human macrophages readily sense cytosolic flagellin. Infection of primary human macrophages with Salmonella elicits robust cell death and IL-1β secretion that is dependent on flagellin. We show that flagellin detection requires a full-length isoform of human Naip. This full-length Naip isoform is robustly expressed in primary macrophages from healthy human donors, but it is drastically reduced in monocytic tumor cells, THP-1, and U937, rendering them insensitive to cytosolic flagellin. However, ectopic expression of full-length Naip rescues the ability of U937 cells to sense flagellin. In conclusion, human Naip functions to activate the inflammasome in response to flagellin, similar to murine Naip5/6.

    View details for DOI 10.4049/jimmunol.1403100

    View details for Web of Science ID 000358070400011

    View details for PubMedID 26109648

  • IMMUNOLOGY. Microbial metabolite triggers antimicrobial defense. Science Brubaker, S. W., Monack, D. M. 2015; 348 (6240): 1207-1208

    View details for DOI 10.1126/science.aac5835

    View details for PubMedID 26068833

  • Innate Immune Pattern Recognition: A Cell Biological Perspective ANNUAL REVIEW OF IMMUNOLOGY VOL 33 Brubaker, S. W., Bonham, K. S., Zanoni, I., Kagan, J. C. 2015; 33: 257-290

    Abstract

    Receptors of the innate immune system detect conserved determinants of microbial and viral origin. Activation of these receptors initiates signaling events that culminate in an effective immune response. Recently, the view that innate immune signaling events rely on and operate within a complex cellular infrastructure has become an important framework for understanding the regulation of innate immunity. Compartmentalization within this infrastructure provides the cell with the ability to assign spatial information to microbial detection and regulate immune responses. Several cell biological processes play a role in the regulation of innate signaling responses; at the same time, innate signaling can engage cellular processes as a form of defense or to promote immunological memory. In this review, we highlight these aspects of cell biology in pattern-recognition receptor signaling by focusing on signals that originate from the cell surface, from endosomal compartments, and from within the cytosol.

    View details for DOI 10.1146/annurev-immunol-032414-112240

    View details for Web of Science ID 000352911900010

    View details for PubMedID 25581309

  • A Bicistronic MAVS Transcript Highlights a Class of Truncated Variants in Antiviral Immunity CELL Brubaker, S. W., Gauthier, A. E., Mills, E. W., Ingolia, N. T., Kagan, J. C. 2014; 156 (4): 800-811

    Abstract

    Bacterial and viral mRNAs are often polycistronic. Akin to alternative splicing, alternative translation of polycistronic messages is a mechanism to generate protein diversity and regulate gene function. Although a few examples exist, the use of polycistronic messages in mammalian cells is not widely appreciated. Here we report an example of alternative translation as a means of regulating innate immune signaling. MAVS, a regulator of antiviral innate immunity, is expressed from a bicistronic mRNA encoding a second protein, miniMAVS. This truncated variant interferes with interferon production induced by full-length MAVS, whereas both proteins positively regulate cell death. To identify other polycistronic messages, we carried out genome-wide ribosomal profiling and identified a class of antiviral truncated variants. This study therefore reveals the existence of a functionally important bicistronic antiviral mRNA and suggests a widespread role for polycistronic mRNAs in the innate immune system.

    View details for DOI 10.1016/j.cell.2014.01.021

    View details for Web of Science ID 000331379800017

    View details for PubMedID 24529381

  • Differential Requirements for NAIP5 in Activation of the NLRC4 Inflammasome INFECTION AND IMMUNITY Lightfield, K. L., Persson, J., Trinidad, N. J., Brubaker, S. W., Kofoed, E. M., Sauer, J., Dunipace, E. A., Warren, S. E., Miao, E. A., Vance, R. E. 2011; 79 (4): 1606-1614

    Abstract

    Inflammasomes are cytosolic multiprotein complexes that assemble in response to infectious or noxious stimuli and activate the CASPASE-1 protease. The inflammasome containing the nucleotide binding domain-leucine-rich repeat (NBD-LRR) protein NLRC4 (interleukin-converting enzyme protease-activating factor [IPAF]) responds to the cytosolic presence of bacterial proteins such as flagellin or the inner rod component of bacterial type III secretion systems (e.g., Salmonella PrgJ). In some instances, such as infection with Legionella pneumophila, the activation of the NLRC4 inflammasome requires the presence of a second NBD-LRR protein, NAIP5. NAIP5 also is required for NLRC4 activation by the minimal C-terminal flagellin peptide, which is sufficient to activate NLRC4. However, NLRC4 activation is not always dependent upon NAIP5. In this report, we define the molecular requirements for NAIP5 in the activation of the NLRC4 inflammasome. We demonstrate that the N terminus of flagellin can relieve the requirement for NAIP5 during the activation of the NLRC4 inflammasome. We also demonstrate that NLRC4 responds to the Salmonella protein PrgJ independently of NAIP5. Our results indicate that NAIP5 regulates the apparent specificity of the NLRC4 inflammasome for distinct bacterial ligands.

    View details for DOI 10.1128/IAI.01187-10

    View details for Web of Science ID 000288532300022

    View details for PubMedID 21282416

  • The N-Ethyl-N-Nitrosourea-Induced Goldenticket Mouse Mutant Reveals an Essential Function of Sting in the In Vivo Interferon Response to Listeria monocytogenes and Cyclic Dinucleotides INFECTION AND IMMUNITY Sauer, J., Sotelo-Troha, K., von Moltke, J., Monroe, K. M., Rae, C. S., Brubaker, S. W., Hyodo, M., Hayakawa, Y., Woodward, J. J., Portnoy, D. A., Vance, R. E. 2011; 79 (2): 688-694

    Abstract

    Type I interferons (IFNs) are central regulators of the innate and adaptive immune responses to viral and bacterial infections. Type I IFNs are induced upon cytosolic detection of microbial nucleic acids, including DNA, RNA, and the bacterial second messenger cyclic-di-GMP (c-di-GMP). In addition, a recent study demonstrated that the intracellular bacterial pathogen Listeria monocytogenes stimulates a type I IFN response due to cytosolic detection of bacterially secreted c-di-AMP. The transmembrane signaling adaptor Sting (Tmem173, Mita, Mpys, Eris) has recently been implicated in the induction of type I IFNs in response to cytosolic DNA and/or RNA. However, the role of Sting in response to purified cyclic dinucleotides or during in vivo L. monocytogenes infection has not been addressed. In order to identify genes important in the innate immune response, we have been conducting a forward genetic mutagenesis screen in C57BL/6 mice using the mutagen N-ethyl-N-nitrosourea (ENU). Here we describe a novel mutant mouse strain, Goldenticket (Gt), that fails to produce type I IFNs upon L. monocytogenes infection. By genetic mapping and complementation experiments, we found that Gt mice harbor a single nucleotide variant (T596A) of Sting that functions as a null allele and fails to produce detectable protein. Analysis of macrophages isolated from Gt mice revealed that Sting is absolutely required for the type I interferon response to both c-di-GMP and c-di-AMP. Additionally, Sting is required for the response to c-di-GMP and L. monocytogenes in vivo. Our results provide new functions for Sting in the innate interferon response to pathogens.

    View details for DOI 10.1128/IAI.00999-10

    View details for Web of Science ID 000286462000014

    View details for PubMedID 21098106

  • Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin NATURE IMMUNOLOGY Lightfield, K. L., Persson, J., Brubaker, S. W., Witte, C. E., von Moltke, J., Dunipace, E. A., Henry, T., Sun, Y., Cado, D., Dietrich, W. F., Monack, D. M., Tsolis, R. M., Vance, R. E. 2008; 9 (10): 1171-1178

    Abstract

    Inflammasomes are cytosolic multiprotein complexes that sense microbial infection and trigger cytokine production and cell death. However, the molecular components of inflammasomes and what they sense remain poorly defined. Here we demonstrate that 35 amino acids of the carboxyl terminus of flagellin triggered inflammasome activation in the absence of bacterial contaminants or secretion systems. To further elucidate the host flagellin-sensing pathway, we generated mice deficient in the intracellular sensor Naip5. These mice failed to activate the inflammasome in response to the 35 amino acids of flagellin or in response to Legionella pneumophila infection. Our data clarify the molecular basis for the cytosolic response to flagellin.

    View details for DOI 10.1038/ni.1646

    View details for Web of Science ID 000259315600016

    View details for PubMedID 18724372