Higgins Lab Department of Microbiology
Harvard Medical School 
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Recent Publications

Tan, J.M.J., Mellouk, N., Osborne, S.E., Ammendolia, D.A., Dyer, D.N., Li, R., Brunen, D., van Rijn, J.M., Huang, J., Czuczman, M.A., Cemma, M.A., Won, A.M., Yip, C.M., Xavier, R.J., MacDuff, D.A., Reggiori, F., Debnath, J., Yoshimori, T., Kim, P.K., Fairn, G.D., Coyaud, E., Raught, B., Muise, A.M., Higgins, D.E., and Brumell, J.H. (2018) An ATG16L1-dependent pathway promotes plasma membrane repair and limits Listeria monocytogenes cell-to-cell spread. Nat. Microbiol. (12):1472-1485. PDF

Cruz-Leal, Y., Grubaugh, D., Nogueira, C.V., Lopetegui-González, I., Del Valle, A., Escalona, F., Laborde, R.J., Alvarez, C., Fernández, L.E., Starnbach, M.N., Higgins, D.E., and Lanio, M.E. (2018) The vacuolar pathway in macrophages plays a major role in antigen cross-presentation induced by the pore-forming protein sticholysin II encapsulated into liposomes. Front. Immunol. 9:2473. PDF

Ghosh, P., and Higgins, D.E. (2018) Listeria monocytogenes infection of the brain. J. Vis. Exp. Oct. 2(140). PDF

Ghosh, P., Halvorsen, E.M., Ammendolia, D.A., Mor-Vaknin, N., O'Riordan, M.X.D., Brumell, J.H., Markovitz, D.M., and Higgins, D.E. (2018) Invasion of the brain by Listeria monocytogenes is mediated by InlF and host cell vimentin. MBio. 9(1): e00160-18. PDF

Grubaugh, D., Regeimbal, J.M., Ghosh, P., Zhou, Y., Lauer, P., Dubensky, T.W. Jr., and Higgins, D.E. (2018) The VirAB ABC transporter is required for VirR regulation of Listeria monocytogenes virulence and resistance to nisin. Infect. Immun. 86(3): e00901-17. PDF

Zhang, T., Abel, S., Abel Zur Wiesch, P., Sasabe, J., Davis, B.M., Higgins, D.E., and Waldor, M.K. (2017) Deciphering the landscape of host barriers to Listeria monocytogenes infection. Proc. Natl. Acad. Sci. U.S.A. 114(24):6334-6339. PDF

Laborde, R.J., Sanchez-Ferras, O., Luzardo, M.C., Cruz-Leal, Y., Fernández, A., Mesa, C., Oliver, L., Canet, L., Abreu-Butin, L., Nogueira, C.V., Tejuca, M., Pazos, F., Álvarez, C., Alonso, M.E., Longo-Maugéri, I.M., Starnbach, M.N., Higgins, D.E., Fernández, L.E., and Lanio, M.E. (2017) Novel adjuvant based on the pore-forming protein sticholysin II encapsulated into liposomes effectively enhances the antigen-specific CTL-mediated immune response. J. Immunol. 198(7):2772-2784. PDF

Osborne, S.E., Sit, B., Shaker, A., Currie, E., Tan, J.M., van Rijn, J., Higgins, D.E., and Brumell, J.H. (2017) Type I interferon promotes cell-to-cell spread of Listeria monocytogenes. Cell. Microbiol. Mar. 19(3). PDF

Picard, M.D., Bodmer, J., Gierahn, T.M., Lee, A., Price, J., Cohane, K., Clemens, V., DeVault, V.L., Gurok, G., Kohberger, R., Higgins, D.E., Siber, G.R., Flechtner, J.B., and Geisler. W.M. (2015) Resolution of Chlamydia trachomatis infection is associated with a distinct T cell response profile. Clin. Vaccine Immunol. 22(11): 1206–1218. PDF

Cemma, M., Lam, G.Y., Stöckli, M., Higgins, D.E., and Brumell, J.H. (2015) Strain-specific interactions of Listeria monocytogenes with the autophagy system in host cells. PLoS One. 10(5): e0125856. PDF

Fattouh, R., Kwon, H., Czuczman, M.A., Copeland, J.W., Pelletier, L., Quinlan, M.E., Muise, A.M., Higgins, D.E., and Brumell, J.H. (2015) The diaphanous-related formins promote protrusion formation and cell-to-cell spread of Listeria monocytogenes. J. Infect. Dis. 211(7): 1185–1195. PDF

Alonso, A.N., Perry, K.J., Regeimbal, J.M., Regan, P.M., and Higgins, D.E. (2014) Identification of Listeria monocytogenes determinants required for biofilm formation. PLoS One. 9(12): e113696. PDF

Czuczman, M.A., Fattouh, R., van Rijn, J.M., Canadien, V., Osborne, S., Muise, A.M., Kuchroo, V.K., Higgins, D.E., and Brumell, J.H. (2014) Listeria monocytogenes exploits efferocytosis to promote cell-to-cell spread. Nature. 509(7499): 230-234. PDF

Grubaugh, D., Flechtner, J.B., and Higgins, D.E. (2013) Proteins as T cell antigens: Methods for high-throughput identification. Vaccine. 31(37): 3805-3810. PDF

Perry, K.J., and Higgins, D.E. (2013) A differential fluorescence-based genetic screen identifies Listeria monocytogenes determinants required for intracellular replication. J. Bacteriol. 195(15): 3331-3340. PDF

Lam, G.Y., Cemma, M., Muise, A.M., Higgins, D.E., and Brumell, J.H. (2013) Host and bacterial factors that regulate LC3 recruitment to Listeria monocytogenes during the early stages of macrophage infection. Autophagy. 9(7): 985–995. PDF

Chen, L., Chen, Z., Baker, K., Halvorsen, E.M., da Cunha, A.P., Flak, M.B., Gerber, G., Huang, Y.H., Hosomi, S., Arthur, J.C., Dery, K.J., Nagaishi, T., Beauchemin, N., Holmes, K.V., Ho, J.W., Shively, J.E., Jobin, C., Onderdonk, A.B., Bry, L., Weiner, H.L., Higgins, D.E., and Blumberg, R.S. (2012) The short isoform of the CEACAM1 receptor in intestinal T cells regulates mucosal immunity and homeostasis via Tfh cell induction. Immunity. 37(5): 930-946. PDF

Picard, M.D., Cohane, K.P., Gierahn, T.M., Higgins D.E., and Flechtner, J.B. (2012) High-throughput proteomic screening identifies Chlamydia trachomatis antigens that are capable of eliciting T cell and antibody responses that provide protection against vaginal challenge. Vaccine. 30(29): 4387-4393. PDF

Lam, G.Y., Czuczman, M.A., Higgins, D.E., and Brumell, J.H. (2012) Interactions of Listeria monocytogenes with the autophagy system of host cells. Adv. Immunol. 113: 7-18. PDF

Lam, G.Y., Fattouh, R., Muise, A.M., Grinstein, S., Higgins, D.E., and Brumell, J.H. (2011) Listeriolysin O suppresses phospholipase C-mediated activation of the microbicidal NADPH oxidase to promote Listeria monocytogenes infection. Cell Host Microbe. 10(6): 627-634. PDF

Kamp, H.D., and Higgins, D.E. (2011) A protein thermometer controls temperature-dependent transcription of flagellar motility genes in Listeria monocytogenes.
PLoS Pathog. 7(8): e1002153. PDF

Moffitt, K.L., Gierahn, T.M., Lu, Y.J., Gouveia, P., Alderson, M., Flechtner, J.B., Higgins, D.E., and Malley, R. (2011) T(H)17-based vaccine design for prevention of Streptococcus pneumoniae colonization. Cell Host Microbe 9(2): 158-165. PDF

Lieberman, L.A., and Higgins, D.E. (2010) Inhibition of Listeria monocytogenes infection by neurological drugs. Int. J. Antimicrob. Agents 35(3): 292-296. PDF

Kamp, H.D., and Higgins, D.E. (2009) Transcriptional and post-transcriptional regulation of the GmaR antirepressor governs temperature-dependent control of flagellar motility in Listeria monocytogenes. Mol. Microbiol. 74(2): 421-435. PDF

Burrack, L.S., Harper J.W., and Higgins, D.E. (2009) Perturbation of vacuolar maturation promotes listeriolysin O-independent vacuolar escape during Listeria monocytogenes infection of human cells. Cell. Microbiol. 11(9): 1382-1398. PDF

Shen, A., Higgins, D.E., and Panne, D. (2009) Recognition of AT-rich DNA binding sites by the MogR repressor. Strucure 17(5): 769-777. PDF

Lieberman, L.A., and Higgins, D.E. (2009) A small-molecule screen identifies the antipsychotic drug pimozide as an inhibitor of Listeria monocytogenes infection. Antimicrob. Agents Chemother. 53(2): 756-764. PDF

Kaser, A., Lee, A.H., Franke, A., Glickman, J.N., Zeissig, S., Tilg, H., Nieuwenhuis, E.E., Higgins, D.E., Schreiber, S., Glimcher, L.H., and Blumberg, R.S. (2008) XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 134(5): 743-756. PDF

Kirchner, M. and Higgins, D.E. (2008) Inhibition of ROCK activity allows InlF-mediated invasion and increased virulence of Listeria monocytogenes. Mol. Microbiol. 68(3): 749-767. PDF

Smithey, M.J., Brandt, S., Freitag, N.E., Higgins, D.E., and Bouwer, H.G. (2008) Stimulation of enhanced CD8 T cell responses following immunization with a hyper-antigen secreting intracytosolic bacterial pathogen. J. Immunol. 180(5): 3406-3416. PDF

Birmingham, C.L., Higgins, D.E., and Brumell, J.H. (2008) Avoiding death by autophagy: interactions of Listeria monocytogenes with the macrophage autophagy system. Autophagy. 4(3): 368-371. PDF

Birmingham, C.L., Canadien, V., Kaniuk, N.A., Steinberg, B.E., Higgins, D.E., and Brumell, J.H. (2008) Listeriolysin O allows Listeria monocytogenes replication in macrophage vacuoles. Nature. 451(7176): 350-354. PDF

Birmingham, C.L., Canadien, V., Gouin, E., Troy, E.B., Yoshimori, T., Cossart, P., Higgins, D.E., and Brumell, J.H. (2007) Listeria monocytogenes evades killing by autophagy during colonization of host cells. Autophagy. 3(5): 442-451. PDF

Lemon, K.P., Higgins, D.E., and Kolter, R. (2007) Flagellar motility is critical for Listeria monocytogenes biofilm formation. J. Bacteriol. 189(12): 4418-4424. PDF

Burrack, L.S. and Higgins, D.E. (2007) Genomic approaches to understanding bacterial virulence. Curr. Opin. Microbiol. 10(1): 4-9. PDF

Alberti-Segui, C., Goeden, K.R. and Higgins, D.E. (2007) Differential function of Listeria monocytogenes listeriolysin O and phospholipases C in vacuolar dissolution following cell-to-cell spread. Cell. Microbiol. 9(1): 179-195. PDF

Shen, A., Kamp, H.D., Gründling, A., and Higgins, D.E. (2006) A bifunctional O-GlcNAc transferase governs flagellar motility through anti-repression. Genes Dev. 20(23): 3283-3295. PDF

Roan, N.R., Gierahn, T.M., Higgins, D.E. and Starnbach, M.N. (2006) Monitoring the T cell response to genital tract infection. Proc. Natl. Acad. Sci. U.S.A. 103(32): 12069-12074. PDF

Yoshida, M., Kobayashi, K., Kuo, T.T., Bry, L., Glickman, J.N., Claypool, S.M., Kaser, A., Nagaishi, T., Higgins, D.E., Mizoguchi, E., Wakatsuki, Y., Roopenian, D.C., Mizoguchi, A., Lencer, W.I. and Blumberg, R.S. (2006) Neonatal Fc receptor for IgG regulates mucosal immune responses to luminal bacteria. J. Clin. Invest. 116(8): 2142-2151. PDF

Shen, A. and Higgins, D.E. (2006) The MogR transcriptional repressor regulates nonhierarchal expression of flagellar motility genes and virulence in Listeria monocytogenes. PLoS Pathog. 2(4): e30. PDF

Bouwer, H.G.A., Alberti-Segui, C., Montfort, M.J., Berkowitz, N.D., and Higgins, D.E. (2006) Directed antigen delivery as a vaccine strategy for an intracellular bacterial pathogen. Proc. Natl. Acad. Sci. U.S.A. 103(13): 5102-5107. PDF

Henry, R., Shaughnessy, L., Loessner, M.J., Alberti-Segui, C., Higgins, D.E. and Swanson, J.A. (2006) Cytolysin-dependent delay of vacuole maturation in macrophages infected with Listeria monocytogenes. Cell. Microbiol. 8(1): 107-119. PDF

Shen, A. and Higgins, D.E. (2005) The 5’ untranslated region-mediated enhancement of intracellular listeriolysin O production is required for Listeria monocytogenes pathogenicity. Mol. Microbiol. 57(5): 1460-1473. PDF

Li, Z., Zhao, X., Higgins, D.E. and Frankel, F.R. (2005) Conditional lethality yields a new vaccine strain of Listeria monocytogenes for induction of cell-mediated immunity. Infect. Immun. 73(8): 5065-5073. PDF

Agaisse, H., Burrack, L.S., Philips, J.A., Rubin, E.J., Perrimon, N. and Higgins, D.E. (2005) Genome-wide RNAi screen for host factors required for intracellular bacterial infection. Science. 309(5738): 1248-1251. PDF

Pan, H., Yan, B., Rojas, M., Shebzukhov, Y.V.,  Zhou,  H., Kobzik, L., Higgins, D.E., Daly, M., Bloom, B.R. and Kramnik, I. (2005) Ipr1 gene mediates innate immunity to tuberculosis. Nature. 434(7034): 767-772. PDF

Boyartchuk, V., Rojas, M., Yan, B., Jobe, O., Hurt, N., Dorfman, D.M., Higgins, D.E., Dietrich, W.F. and Kramnik, I. (2004) The host resistance locus sst1 controls innate immunity to Listeria monocytogenes infection in immunodeficient mice. J. Immunol. 173(8): 5112-5120. PDF

Gründling, A., Burrack, L.S., Bouwer, H.G.A. and Higgins, D.E. (2004) Listeria monocytogenes regulates flagellar motility gene expression through MogR, a transcriptional repressor required for virulence. Proc. Natl. Acad. Sci. U.S.A. 101(33): 12318-12323. PDF

Starks, H., Bruhn, K.W., Shen, H., Barry, R.A., Dubensky, T.W., Brockstedt, D., Hinrichs, D.J., Higgins, D.E., Miller, J.F., Giedlin, M. and Bouwer, H.G.A. (2004) Listeria monocytogenes as a vaccine vector: virulence attenuation or existing antivector immunity does not diminish therapeutic efficacy. J. Immunol. 173(1): 420-427. PDF

Hu, P.Q., Tuma-Warrino, R.J., Bryan, M.A., Mitchell, K.G., Higgins, D.E., Watkins, S.C. and Salter, R.D. (2004) Escherichia coli expressing recombinant antigen and listeriolysin O stimulate class I-restricted CD8+ T cells following uptake by human APC. J. Immunol. 172(3): 1595-1601. PDF

Gründling, A., Gonzalez, M.D. and Higgins, D.E. (2003) Requirement of the Listeria monocytogenes broad-range phospholipase PC-PLC during infection of human epithelial cells. J. Bacteriol. 185(21): 6295-6307. PDF

Radford, K.J., Higgins, D.E., Pasquini, S., Cheadle, E.J., Carta, L., Jackson, A.M., Lemoine, N.R. and Vassaux, G. (2002) A recombinant E. coli to promote MHC class I-dependent antigen presentation: application to cancer immunotherapy. Gene Therapy 9(21): 1455-1463. PDF

Dancz, C.E., Haraga, A., Portnoy, D.A. and Higgins, D.E. (2002) Inducible control of virulence gene expression in Listeria monocytogenes: temporal requirement of listeriolysin O during intracellular infection. J. Bacteriol. 184(21): 5935-5945. PDF