Dept. of Microbiology and Immunobiology
Harvard Medical School
77 Avenue Louis Pasteur
Boston, MA 02115
Bacterial pathogens that grow within human cells are responsible for multiple diseases and millions of deaths worldwide. The primary goal of our research is to elucidate both the pathogen and host cell-specific mechanisms involved in the growth and spread of intracellular bacterial pathogens. Specific areas of emphasis include: 1) characterizing host-specific factors that are required for intracellular bacterial pathogenesis, 2) determining the function of virulence factors and mechanisms regulating virulence gene expression during intracellular infection, 3) identifying pathogen-specific antigens that stimulate protective cellular immune responses and 4) developing novel prophylactic and therapeutic strategies for intracellular pathogens.
We take a multidisciplinary approach in our investigations employing molecular genetics, high-resolution microscopy, structural biology, tissue culture, and mouse infection models. Because of the rich history as a model intracellular pathogen for immunological and cell biological research, we primarily utilize the bacterium Listeria monocytogenes for our studies. Building upon extensive expertise in the areas of microbial pathogenesis, immunology, and the cell biology of infection, our group has pioneered multiple approaches and made significant contributions to understanding the mechanisms of intracellular bacterial pathogenesis and the host immune response to infection.
Osborne, S.E., Sit, B., Shaker, A., Currie, E., Tan, J.M., van Rijn, J., Higgins, D.E., Brumell, J.H. (2017) Type I interferon promotes cell-to-cell spread of Listeria monocytogenes. Cell. Microbiol. 19(3): e12660.
Picard, M.D., Bodmer, J.L., 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., 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.
Czuczman, M.A., Fattouh, R., van Rijn, J.M., Canadien, V., Osborne, S., Muise, A.M., Kuchroo, V.K., Higgins, D.E., Brumell, J.H. (2014) Listeria monocytogenes exploits efferocytosis to promote cell-to-cell spread. Nature 509(7499): 230-234.
Perry, K.J., Higgins, D.E. (2013) A differential fluorescence-based genetic screen identifies Listeria monocytogenes determinants required for intracellular replication. J. Bacteriol. 195(15): 3331-3340.
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., 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.
Kamp, H.D., Higgins DE. (2011) A protein thermometer controls temperature-dependent transcription of flagellar motility genes in Listeria monocytogenes. PLoS Pathog. 7(8): e1002153.
Moffitt, K.L., Gierahn, T.M., Lu, Y.J., Gouveia, P., Alderson, M., Flechtner, J.B., Higgins, D.E., Malley, R. (2011) T(H)17-based vaccine design for prevention of Streptococcus pneumoniae colonization. Cell Host Microbe. 9(2): 158-165.
Burrack, L.S., Harper, J.W., 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.