Florian Douam, Ph.D.
Assistant Professor of Microbiology
Peter Paul Career Development Professor
620 Albany Street, NEIDL 501
BS Université François Rabelais, Tours, France
PhD École Normale Supérieure de Lyon, Lyon, France
A large number of challenging viral diseases, such as viral hepatitis, AIDS, Dengue fever or yellow fever are caused by viruses that display a very narrow host tropism often restricted to human. For this reason, studying the biology of human-tropic viruses in vivo, and understanding how they interact with human components over time and space, has remained a challenging endeavor.
Humanized mice, i.e. mice engrafted with human tissues, have emerged as powerful tools for studying the infectious cycle of a broad range of human(-tropic) pathogens in vivo (Figure 1). Recent improvements in engraftment protocols and genetic engineering have opened unprecedented opportunities for the generation of more advanced humanized mouse systems able to recapitulate more faithfully human biological processes, such human immune responses against viral pathogens.
Figure 1. Schematic representation of the advantages of humanized mouse systems (from green to orange) over mouse models (grey) and the “human” model (red). Humanization is represented by a color gradient going from white to red (adapted from Douam et al. Current Opinion of Virology. 2018).
Located at the National Emerging Infectious Disease Laboratories (NEIDL), our laboratory aims at using and developing advanced humanized mouse models to identify and characterize fundamental human immunological mechanisms and human-virus interactions that govern viral pathogenicity and immunogenicity during virus infection.
By combining advanced humanized mouse systems with the unique biocontainment facilities of the NEIDL and the most recent “omic” technologies, our research program specifically revolves around four major axes (Figure 2):
- What are the spatiotemporal immunological signatures associated with viral immunogenicity and pathogenicity in human in vivo?
- Can we probe specific human-virus interactions that underlie these spatiotemporal signatures?
- How host and viral genetic heterogeneity impact these molecular interactions and ultimately the associated immunological signatures?
- How immunological history and metabolic status regulate viral virulence and immunogenicity in vivo?
Figure 2. Schematic representation of the research axes of the laboratory. Research axes are labelled from 1 to 4 in red discs and are respectively related to the four research questions listed above.
Additionally, our laboratory is also interested in understanding how human non-coding RNAs modulate the cell-intrinsic immune detection of flavivirus (such as Dengue virus, Zika virus and yellow fever virus), as well as identifying human proteins that regulate flavivirus entry into their target cells.
Altogether, we believe that our scientific approach will contribute to significantly enhance our understanding of the human immune responses to some of the most challenging viral pathogens. We are also confident that our research will provide a molecular rational for the design of novel and potent live-attenuated viral-based vaccines against pathogens that pose major health and economic concerns.
- Douam F, Ziegler CGK, Hrebikova G, Fant B, Leach R, Parsons L, Wang W, Gaska JM, Winer BY, Heller B, Shalek AK, Ploss A. 2018. Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses. Nat. Commun. 9:5031. PMID: 30487575
- Douam F, Ploss A. 2018. Yellow Fever Virus: Knowledge Gaps Impeding the Fight Against an Old Foe. Trends Microbiol. 26:913-928. PMID: 29933925
- Douam F, Ploss A. 2018. The use of humanized mice for studies of viral pathogenesis and immunity. Curr. Opin. Virol. 29:62-71. PMID: 29604551
- Douam F, Soto Albrecht YE, Hrebikova G, Sadimin E, Davidson C, Kotenko SV, Ploss A. 2017. Type III interferon-mediated signaling is critical for controlling live-attenuated yellow fever virus infection in vivo. mBio 8: e00819-17. PMID: 28811340
- Douam F, Hrebikova G, Soto Albrecht YE, Sellau J, Sharon Y, Ding Q, Ploss A. 2017. Single-cell tracking of flavivirus RNA uncovers species-specific interactions with the immune system dictating disease outcome. Nat. Commun. 8:14781. PMID: 28290449
- Douam F, Gaska JM, Winer BY, Ding Q, von Schaewen M, Ploss A. 2015. Genetic Dissection of the Host Tropism of Human-Tropic Pathogens. Annu. Rev. Genet. 49:21-45. PMID: 26407032
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