BBS Faculty Member - Darren Higgins

Darren Higgins

Department of Microbiology

Harvard Medical School
New Research Building, Room 854
77 Ave. Louis Pasteur
Boston, MA 02115
Tel: 617-432-4156
Fax: 617-432-4787
Email: dhiggins@hms.harvard.edu
Visit my lab page here.



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, spread, and virulence of intracellular bacterial pathogens. We take a multidisciplinary approach in our investigations employing molecular genetics, cell biology, immunology, high-resolution microscopy, structural biology, tissue culture and mouse infection models.

Because of its rich history as a model intracellular pathogen for immunological and cell biological research, we primarily utilize the bacterium
Listeria monocytogenes for our studies. L. monocytogenes is a foodborne pathogen capable of causing severe life-threatening infections in humans, including meningitis and encephalitis. Current research areas include: determining the mechanisms of host cell invasion, cell-to-cell spread, and colonization of distal sites within the host, such as the brain. Furthermore, we are using organoid infection models to determine the molecular mechanisms of host defense and bacterial virulence strategies, studying the coordinate regulation of bacterial gene expression required for pathogenesis, and characterizing pathogen-specific antigenic targets and host cell mediators that lead to protective T cell-mediated immunity.



Last Update: 11/4/2019



Publications

For a complete listing of publications click here.

 


 

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.

Tan, J., Mellouk, N., Osborne, S.E., Canadien, V., Brunen, D., van Rijn, J., Czuczman, M.A., Cemma, M., Fattouh, R., Lam, G.Y., Huang, J., Muise, A.M., Kim, P.K., MacDuff, D., Virgin, H.W., Reggiori, F., Higgins, D.E. and Brumell, J.H. (2018) An ATG16L1-dependent pathway promotes plasma membrane repair and limits pathogen spread.
Nature Microbiology 3(12): 1472-1485.

Grubaugh, D., Regeimbal, J.M., Ghosh, P., Zhou, Y., Lauer, P., Dubensky, T.W. 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.

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.

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.



© 2016 President and Fellows
of Harvard College