Herve Francois Agaisse MSc, PhD

Associate Professor of Microbial Pathogenesis

Research Interests

Host/pathogen interaction; Shigella; Chlamydia; Vaccinia virus; Listeria; Dissemination; Actin-based motility; Non-vesicular lipid trafficking; Tyrosine kinase signaling; Type III secretion system

Research Summary

We investigate the cellular and molecular mechanisms underlying host/pathogen interaction. Our research efforts have been divided in two separate but related areas. First, we have pioneered and perfected innovative genetic approaches to systematically interrogate the human genome and determine the host genes involved in a given cellular process. Second, we have applied our expertise in large-scale genetic approaches to uncover the cellular processes supporting the development and dissemination of several important human pathogens. Ongoing projects include:

(1) We have established that Chlamydia trachomatis manipulates the non-vesicular lipid transfer protein CERT in order to build a replicative membrane-bound compartment, the Chlamydia inclusion. We are currently defining the host pathogen interface underlying the formation of contact sites between the Chlamydia inclusion and the endoplasmic reticulum (ER) through the interaction of cellular factors such as CERT and the bacterial factor IncD.

(2) We have established that vaccinia virus dissemination not only relies on the activity of the N-WASP/ARP2/3 pathway, as previously described, but also on the activity of the Rac1/FHOD1 pathway, as discovered by our group. We are currently defining the host/pathogen interface supporting the functional integration of these two pathways through the activity of signaling components identified during the discovery phase of this project, as well as viral components recently identified by our group.

(3) We have established that S. flexneri hijacks lipid kinases to manipulate the lateral junctions of polarized epithelial cells and spread from cell to cell. We are currently defining the host/pathogen interface supporting this dissemination process through the activity of cellular components identified during the discovery phase of this project, as well as bacterial factors recently identified by our group.

Selected Publications

  • Talman A, Chong R, Chia J, Svitkina, T and Agaisse H. Actin network disassembly powers Listeria monocytogenes dissemination. J Cell Sci. 2013, in press.
  • Alvarez D and Agaisse H. The formin FHOD1 and the small GTPase Rac1 promote vaccinia virus actin-based motility. J Cell Biol. 2013, 202(7):1075-1090.
  • Derré I and Agaisse H. The lipid transfer protein CERT interacts with the Chlamydia protein IncD and participates in ER-Chlamydia inclusion membrane contact sites. PLoS Pathogens. 2011, 7(6):e1002092.
  • Chong R, Swiss R, Briones G, Stone KL, Gulcicek EE and Agaisse H. Regulatory mimicry in Listeria monocytogenes actin-based motility. Cell Host Microbe. 2009, 6(3):268-78.
  • Krishnan M, Ng A, Sukumaran B, Gilfoy, FD, Uchil P, Sultana A, Brass A, Adametz R, Tsui M, Qian F, Montgomery R, Lev S, Mason PW, Koski RA, Elledge SJ, Xavier RJ, Agaisse H and Fikrig E. RNA interference screen for human genes associated with West Nile Virus infection. Nature. 2008. 11;455(7210):242-5.
  • Derre I, Pypaert M, Dautry-Varsat A, Agaisse H. RNAi Screen in Drosophila Cells Reveals the Involvement of the Tom Complex in Chlamydia Infection. PLoS Pathog. 2007. 3(10):1446-58.
  • Agaisse, H., Burrack, L., Philips, J., Perrimon N. and Darren Higgins D. (2005). Genome-wide RNAi screen for host factors required for intracellular bacterial infection. Science 309(5738):1248-51.

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