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Hervé
Agaisse
Assistant Professor Microbial Pathogenesis
Ph.D. Pasteur Institute 1996
e-mail: herve.agaisse@yale.edu
phone: (203) 737-2404 |
Research Interests
Multicellular organisms are continuously exposed to pathogenic microorganisms
and have evolved sophisticated mechanisms that protect them from infection.
Over the past decade, a fascinating notion has emerged: the mechanisms
involved in innate immunity have been conserved throughout evolution.
Taking advantage of this situation, we are using Drosophila melanogaster
as a genetic system to investigate biological processes related to the
mammalian innate immune response.
In a first aspect
of our research program, we use the power of Drosophila genetics
to investigate how various aspects of the immune response are integrated
at the level of an organism. In particular, we study the role of Drosophila
blood cells in the response to stressful conditions. Our main focus
is to understand how blood cells detect stressful events and subsequently
convey this information to immune organs through the production of signaling
molecules. Altogether, our genetic approach in Drosophila will
potentially lead to the identification of uncovered signaling components
that may be relevant to the immune response in mammals.
In a second aspect
of our research program, we use Drosophila cell lines to model
the development of human intracellular pathogens. We have recently completed
a full-genome RNAi-based screen that led to the identification of host
factors involved in the development of Listeria, a human cytosolic
intracellular pathogen. We are now conducting similar screens with intracellular
pathogens displaying a similar or a different life style, such as Shigella
and Chlamydia. Importantly, we use siRNA-based gene expression
silencing methodologies to test in a mammalian system the functional
relevance of the identified host factors.
Selected References
Chong R, Swiss R, Briones G, Stone KL, Gulcicek EE, Agaisse, H. Regulatory mimicry in Listeria monocytogenes actin-based motility (2009). Cell Host Microbe.
6(3):268-78. PDF
Krishnan MN, Ng A, Sukumaran B, Gilfoy FD, Uchil PD, Sultana H, Brass AL, Adametz R, Tsui M, Qian F, Montgomery RR, Lev S, Mason PW, Koski RA, Elledge SJ, Xavier RJ, Agaisse H, Fikrig E. RNA interference screen for human genes associated with West Nile virus infection (2008). Nature.
455(7210):242-5. PDF
Derré I, Pypaert M, Dautry-Varsat A, Agaisse H. RNAi screen in Drosophila cells reveals the involvement of the Tom complex in Chlamydia infection (2007). PLoS Pathog. 3(10):1446-58. PDF
Agaisse, H., Burrack, L., Philips, J., Perrimon N. and Darren Higgins
D. Genome-wide RNAi screen for host factors required for intracellular
bacterial infection. Science.
2005. 309(5738):1248-51. PDF
Agaisse H, Perrimon N. The role of JAK/STAT signaling in Drosophila immune responses (2004). Immunol Rev. 198:72-82. PDF
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