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VIDALAIN Pierre-Olivier

DR

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Université Paris Descartes
45 rue des Saints-Pères
75006 Paris
UMR8601
Chimie, Biologie, Modélisation et Immunologie pour la thérapie
Porte R267, 2ème étage
Tél. : +33 (0) 1 70 64 99 53
Contact : Pierre-Olivier Vidalain

Career and Laboratories

Since October 2015: Directeur de Recherche (CNRS, DR2), Team « Chemistry & Biology, Molecular Modeling and Immunology for Therapies », UMR-8601, Université Paris-Descartes.
2009-2014: Chargé de Recherche (CNRS, CR1), « Viral Genomics and Vaccination Unit », UMR-3569, Institut Pasteur.
2005-2009: Chargé de Recherche (CNRS, CR2), “High-throughput mapping of virus-host protein interactions”, Frédéric Tangy’s Team « Viral Genomics and Vaccination Unit », URA-3015, Institut Pasteur.
2002-2005: Post-Doc, “High-throughput mapping of C. elegans protein-protein interaction network”, Dr. Marc Vidal’s group, Dana-Farber Cancer Institute (Boston, USA).
1998-2002: Ph.D Student, “Virus interactions with immune system: measles virus infection as a model”, Pr. Chantal Rabourdin-Combe’s group, INSERM-U503, IFR-128 BioSciences Lyon-Gerland.

Research topics

Interferons (IFNs) are essential cytokines that play a central role in the innate immune response against viruses and cancer. Once bound to their membrane receptor, they induce a large panel of cellular factors that interfere with multiple steps of virus replication cycle, but also promote apoptosis of both infected and tumor cells. They also contribute to activate the adaptive immune response, and the development of antigen-specific lymphocytes and antibodies. However, despite such benefits, IFNs tend to have deleterious effects when expressed over a long period of time as a consequence of chronic viral infections, genetic disorders or environmental factors. This is often associated to immunosuppression, such as in AIDS, or auto-inflammatory diseases such as lupus or psoriasis.
We are interested in natural and synthetic compounds that impact the innate immune response by modulating IFN production, with specific interests in environmental pollutants, xenobiotics, and stress-associated metabolites as potential modulators of the innate immune response. Indeed, their impact on the IFN response has not been systematically evaluated despite clear evidences of their influence on immunity. In theory, any molecule capable of inhibiting the IFN response could increase the susceptibility of individuals to microbial infections or cancer, but could be used as a therapy against auto-inflammatory diseases. Conversely, compounds causing some chronic activation of the innate immune response could be at the onset of chronic inflammatory diseases such as asthma or lupus, but could be converted into chemical therapies for boosting the immune response.
To identify such modulators of the innate immune response, we have developed a high-throughput functional assay based on human peripheral blood mononuclear cells (PBMCs). In this system, tested compounds are incubated first in the presence of PBMCs for few hours, and then stimulated or not with ligands of Toll-like receptors (TLR) to induce the innate immune response. Later on, culture supernatants are collected, and IFNs secreted by PBMCs are quantified using a highly sensitive reporter cell line. Therefore, this assay can be used to identify inducers IFNs but also inhibitors, when performed in the presence of TLR ligands. This cellular assay has been used to screen thousands of molecules from libraries of artificial compounds, as well as collections of metabolites and xenobiotics. A dozen of compounds were identified for their capacity to inhibit IFN secretion by activated PBMCs. Quite unexpectedly, this list includes natural byproducts of cellular metabolism, few toxins and some widely used medecines that are sold over the counter. Altogether, results obtained validate our screening pipeline on PBMCs to identify artificial or natural modulators of the innate immune response. We are now validating the immunosuppressive properties of these molecules, and deciphering their mode of action to estimate their potential impact in vivo.

Recent publications

  • Khiar S, Lucas-Hourani M, Nisole S, Smith N, Helynck O, Bourgine B, Ruffié C, Herbeuval JP, Munier-Lehmann H, Tangy F, Vidalain PO. Identification of a small molecule that primes the type I interferon response to cytosolic DNA. Scientific Reports. 2017 31;7(1):2561

  • Grandin C, Hourani ML, Janin YL, Dauzonne D, Munier-Lehmann H, Paturet A, Taborik F, Vabret A, Contamin H, Tangy F, Vidalain PO. Respiratory syncytial virus infection in macaques is not suppressed by intranasal sprays of pyrimidine biosynthesis inhibitors. Antiviral Res. 2016 Jan;125:58-62.

  • Lucas-Hourani M, Munier-Lehmann H, El Mazouni F, Malmquist NA, Harpon J, Coutant EP, Guillou S, Helynck O, Noel A, Scherf A, Phillips MA, Tangy F, Vidalain PO, Janin YL. Original 2-(3-Alkoxy-1H-pyrazol-1-yl)azines Inhibitors of Human Dihydroorotate Dehydrogenase (DHODH). J Med Chem. 2015 Jun 58(14):5579-98

  • Grandin C, Lucas-Hourani M, Clavel M, Taborik F, Vabret A, Tangy F, Contamin H, Vidalain PO. Evidence for an Intranasal Immune Response to Human Respiratory Syncytial Virus Infection in Cynomolgus Macaques. J. Gen. Virol. 2015 Apr 96(4):782-92.

  • Munier-Lehmann H, Lucas-Hourani M, Guillou S, Helynck O, Gigliola Z, Noel A, Tangy F, Vidalain PO, Janin Y. Original 2-(3-alkoxy-1H-pyrazol-1-yl)pyrimidine derivatives as inhibitors of human dihydroorotate dehydrogenase (DHODH). J. Med. Chem. 2015 Jan 58(2):860-77