PROJECT
SUPERVISORS

Project Supervisor

Philippe Pierre

Background

Dr. Philippe Pierre is an international leader in dendritic cell biology and innate immunity research. During his Ph.D at EMBL (Heidelberg, Germany), he characterized the microtubule-binding protein CLIP-170. During a post-doctoral research period at Yale University School of Medicine (USA), he worked on MHC II-restricted antigen presentation. In 2000, he created his laboratory at the Centre d’Immunologie de Marseille-Luminy (CIML, France) focusing on the cell biology of dendritic cell activation by microbes with projects studying membrane trafficking, stress pathways, autophagy, while initiating systemic ‘omics” analysis. Dr. Pierre has published over 110 articles in peer-reviewed journals (including Nature, EMBO J., PNAS, Nature Com, Cell Metabolism).

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Dr. Pierre is a member of the EMBO YIP and FSER programs, and serves on the editorial boards of Open Biology and Frontiers in Immunology. P. Pierre received the "Jean-Marie Legoff 2015 Prize" for molecular immunology from the French Academy of Sciences. He is currently the director of CIML and is professor-adjunct of the University of Aveiro (IBiMED, Portugal) and the Shanghai Institute of Immunology (SII, PRC).

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Research

The team studies the changes occurring during dendritic cell (DC) activation by pathogens. In addition to our work on the importance of endosomal proteolysis and natural protease inhibitors to control MHC II transport, we have focussed on the fate of endogenous antigens and the role of ubiquitination in their degradation. We discovered dendritic cell aggresome-like induced structures (DALIS) and the role of autophagy for DRiPs processing, DALIS formation and presentation by MHC molecules.

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Moreover, we showed the involvement of MARCH-ubiquitin ligases in the control of MHC expression, in parallel to the importance of the small RNA miR-155 in controlling DCs activation. The observation that regulation of mRNA translation and induction of stress pathways are central to DC function, motivated our most recent work on the role of the integrated stress response in the control of type I IFN transcription and translation during microbe detection. The laboratory also developed powerful technologies to monitor protein synthesis and energy metabolism by flow cytometry that are now used worldwide.

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Publications

Mendes A., Gigan J. P., Rodriguez Rodrigues C., Choteau S. A., Sanseau D., Barros D., Almeida C., Camosseto V., Chasson L., Paton A. W., Paton J. C., Argüello R. J., Lennon-Dumenil A.-M., Gatti E. and Pierre P. (2020) Proteostasis in dendritic cells is controlled by the PERK signaling axis independently of ATF4. Life Sci Alliance 21, 4(2).

Argüello RJ, Combes AJ, Char R, Gigan JP, Baaziz AI, Bousiquot E, Camosseto V, Samad B, Tsui J, Yan P, Boissonneau S, Figarella-Branger D, Gatti E, Tabouret E, Krummel MF, Pierre P. (2020) SCENITH: A Flow Cytometry-Based Method to Functionally Profile Energy Metabolism with Single-Cell Resolution. Cell Metabolism 32,1063-1075.

Reverendo M., Argüello RJ., Polte C., Valečka J., Camosseto V., Auphan-Anezin N., Ignatova Z., Gatti E. and Pierre P. (2019) Polymerase III transcription is necessary for T cell priming by dendritic cells. Proc. Natl. Acad. Sci. U S A. doi: 10.1073/pnas.1904396116.

Combes A, Camossetto V, N'Guessan P., Argüello R.J., Mussard J., Caux C., Bendriss-Vermare N., *Pierre P. and *Gatti E. (2017), BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells. Nat Commununications 8, 913, * Co-last authors.

Dalet A., Argüello R.J., Combes L., Spinelli L., Jaeger S., Fallet M., Vu Manh T-P, Mendes A., Perego J., Reverendo M., Camosseto V., Dalod M., Weil T., Santos M. A. S. Gatti E. and Pierre P. (2017) Protein synthesis inhibition and GADD34 control IFN-beta heterogeneous expression in response to dsRNA. EMBO J. 15, 761-782.