Gaëtan Barbet, PhD

Dr. Gaëtan Barbet is an Assistant Professor, Department of Pediatrics, Department of Pharmacology at the Child Health Institute of NJ, Rutgers Robert Wood Johnson Medical School. He received his Master's degree in Immunology for the Pasteur Institute and the University of Paris VII, Denis Diderot in 2005 and obtained his PhD in 2009 for his work on the ion channel TRPM4 on innate immune cells at the Bichat Medical School, University of Paris VII. Dr. Barbet learnt cutting-edge microscopy techniques in the laboratory of Dr. Michael Dustin at NYU before joining the laboratory of Dr. Julie Magarian Blander at the Icahn School of Medicine at Mount Sinai and then at the Jill Roberts Institute for Research on Inflammatory Bowel Diseases at Weill-Cornell Medicine where he was appointed Instructor. In Dr. Blander laboratory, Dr. Barbet worked on the biology of mononuclear phagocytes upon the recognition of dead cells, live or dead bacteria or viruses. Dr. Barbet joined the faculty of the Robert Wood Johnson Medical School in January 2021.

Dr. Barbet is an accomplished immunologist specialized in the biology of dendritic cells (DCs), macrophages, and monocytes. His work led to various publications in high-impact journals.

• Dr. Barbet’s work during his Ph.D. focused on the regulation of calcium homeostasis in innate immune cells by the ion channel TRPM4. For instance, in absence of TRPM4, a calcium overload occurs in DCs after bacterial stimulation without affecting the upregulation of costimulatory molecules but dramatically decreased their migratory capacities both in vitro and in vivo (Barbet G, et al. Nat. Immunol. 2008). These pioneering observation on calcium signaling in innate immune cells demonstrate the necessity of a tight calcium regulation for adequate innate immune functions.

• During his post-doctoral tenure, Dr. Barbet worked on the role of apoptosis in intestinal epithelial cells (IECs) and intestinal homeostasis. Dr. Barbet developed and published an experimental mouse model to study how innate immune cells sense and respond to apoptosis. In absence of inflammation, specific populations of dendritic cell and macrophages responsible for apoptotic IEC clearance were identified and characterized by transcriptomic analysis. This work allowed to identify a shared a common “suppression of inflammation” signature and that several of the genes differentially expressed by phagocytes bearing apoptotic IEC overlapped with susceptibility genes for inflammatory bowel disease (IBD, Cummings RJ, Barbet G, et al. Nature 2016).

• Dr. Barbet also worked on elucidating the reasons why live vaccines have historically provided superior protection than their dead counterparts. This work showed that the detection of microbial viability heightens humoral response, controls follicular T helper cell differentiation and germinal center formation. Indeed, during E. coli infection, bacterial mRNA orchestrates unique innate responses through the signaling adaptor TRIF. These responses are elicited specifically in mice by a live vaccine and can be recapitulated with a dead vaccine complemented with bacterial RNA. These new finding hold the promise of safely achieving the efficacy of live vaccines by improving the performance of existing dead vaccines (Barbet G, et al. Immunity 2018). This work hold the promise to obtain vaccine efficacy observed with live vaccine but with the safety of killed vaccines.

Immunology, Innate Immune cells, Inflammation, Mononuclear Phagocytes, Calcium Signaling, Inflammasome, Mucosal Immunology, IgA production, mucosal vaccine.

The Barbet laboratory studies the biology of mononuclear phagocytes such as monocytes, dendritic cells and macrophages. At the intracellular level, the laboratory is interested in the calcium homeostasis and how this second messenger is involved in the sensing of the environment of mononuclear phagocytes. At the intercellular level, we are investigating how mononuclear phagocytes interact with the other immune cells especially at the mucosal surfaces.

The Barbet laboratory is specialized in the biology and function of mononuclear phagocytes (MPs) such as macrophages, dendritic cells and monocytes. The laboratory opened in 2021 and develops an Innate Immunity Research Program centered around the functions of mononuclear phagocytes in various settings of infection, cell death, autoimmunity, cancer and vaccine strategies.

• The Barbet laboratory is initiating an unprecedented platform to study the activation of MPs by live cell imaging techniques both in vitro and in vivo, with a particular focus on the regulation of the calcium homeostasis. We are currently dissecting the calcium mobilization induced by different bacterial stimuli to determine how it shape the early innate responses and to better understand how MPs tailor the immune response to the type of threat they encountered.

• In the front of adaptive cellular responses, Dr. Barbet studied the cross-presentation of phagocytic antigens that relies on Toll-like receptor (TLR)-dependent recruitment of MHC-I molecules to phagosomes. In this process, the transporter TAP shuttles cytosolic peptides, derived from endogenous cellular or microbial proteins, into the endoplasmic reticulum (ER) lumen for loading onto MHC-I molecules. This study uncovered the existence of a non-canonical pathway of cross-presentation mobilized in DCs upon viral inhibition or genetic deletion of TAP, allowing CD8 T cell activation in vitro and in vivo using a mouse model of influenza virus infection. This efficient alternative cross-presentation pathway, independent of TAP offer promises for anti-viral and anti-cancer vaccinal strategies (Barbet G*, Nair-Gupta P*, et al. Nat. Immunol. 2021).

• At mucosal sites, our preliminary results indicate that the pathways leading to protective antibodies in the intestines are different to the ones elicited in conventional vaccines. Hence, we are also developing a mucosal immunology program to understand the mechanism leading to antibody production in the intestines in the aim of developing vaccine strategies tailored for mucosal surfaces. In this effort to investigate how MPs are responding to an environment favorable for protective antibody production, we are also studying how these cells sense epithelial cell death which is a hallmark of Inflammatory Bowel Diseases such as Crohn’s disease. By using those two complementary approaches, we aim to understand how MPs contribute in orchestrating tissue protection through promoting antibody protection and tissue homeostasis in dampening inflammation and promoting tissue repair.

• BarbetG*, Nair-GuptaP*, SchotsaertM, YeungST, SeyfferF, MetreveliG, GardnerT, ChoiA, TortorellaD, TampéR, KhannaKM, García-SastreA, and Magarian BlanderJM. Non-canonical TLR-Independent Cross-presentation in Dendritic Cells Upon TAP Blockade. Nat. Immunol. 2021 Apr. 22, 497–509. *These authors contributed equally.

• Barbet G, Blander JM. A key ingredient for priming killer T cells. Science. 2018 Nov 9;362(6415):641-642. doi: 10.1126/science.aav3683. 

• Blander JM, Barbet G. Exploiting vita-PAMPs in vaccines. Curr. Opin. Pharmacol. 2018 Jun 8;41:128-136. doi: 10.1016/j.coph.2018.05.012.

• Barbet G, Sander LE, Geswell G, Leonardi I, Cerutti A, Iliev Iand Blander JM Sensing microbial viability through bacterial RNA augments T follicular helper cell and antibody responses. Immunity. 2018 Mar 20;48(3):584-598.e5. doi: 10.1016/j.immuni.2018.02.015.

• Barbet G*, Demion M*, Moura IC*, Serafini N, Léger T, Vrtovsnik F, Monteiro RC, Guinamard R, Kinet JP, Launay P. The calcium-activated nonselective cation channel TRPM4 is essential for the migration but not the maturation of dendritic cells. Nat Immunol. 2008 Oct;9(10):1148-56