CV Science

Marc Daëron MD, PhD

Course and current status

Education

M.D. (Doctorat d’état en Médecine), Fac. Med. St-Antoine, U. Paris 6 (1972)

Ph.D. (Doctorat d’état en Biologie humaine), U. Paris 6 (1980)

Master 2 Logique et philosophie des sciences et de la connaissance, U. Paris-Sorbonne (2014)

Positions held

1972-1974: Full-time internship, FRM and LNCC scholarships. Laboratoire d'immunopathologie et d'immunologie expérimentale, Inserm U. 23, Dir. Dr G.-A. Voisin, Hôpital Saint-Antoine, Paris.

1974-1976: Post-doctoral Fellow: Department of Experimental Surgery, Dir. Dr J. Gordon, McGill University, Montréal, Québec, Canada.

1976-1980: Attaché de recherche at Inserm, Laboratoire d'immunopathologie et d'immunologie expérimentale, Inserm U. 23, Dir. Dr G.-A. Voisin, Hôpital Saint-Antoine, Paris.

1980-1982: Chargé de recherche at Inserm / Post-doctoral Fellow, Department of Basic Immunology, Dir. Dr K. Ishizaka, The Johns Hopkins University School of Medicine Baltimore, Maryland, USA ; Recipient of Philippe Foundation and Lillia Babbit Hyde Foundation bursaries. .

1982-1989: Chargé de recherche de 1e classe at Inserm, Laboratoire d'immunologie cellulaire et clinique, Inserm U. 255, Dir. Dr W. H. Fridman, Institut de recherches scientifiques sur le cancer (IRSC), Villejuif (1982-83), Institut Curie, Paris (1983-89).

1989-1996: Directeur de Recherche de 2e classe at Inserm, Laboratoire d'Immunologie Cellulaire et Clinique, Inserm U. 255, Dir. Dr W. H. Fridman, Institut Curie, Paris ; Visiting Scientist, Laboratory of Molecular Allergy and Immunology, Dir. Dr J.-P. Kinet, National Institutes of Health, Rockville, Maryland, USA (Sept. 1993).

1996-2003: Directeur de recherche de 1e classe at Inserm, Laboratoire d'Immunologie Cellulaire et Clinique, Inserm U. 255, Dir. Pr W. H. Fridman, Institut Curie, Paris (1996-2001), Institut biomédical des Cordeliers, Paris (2001-2003). Visiting Scientist, Laboratory of Molecular Genetics and Immunology, Dir. Dr. J. V. Ravetch, The Rockefeller University, New York, USA (July 2002).

2003-2012: Directeur de l'Unité de recherche Allergologie Moléculaire & Cellulaire, Institut Pasteur, Paris (2003-2012); Directeur de l’Unité Inserm 760, Institut Pasteur, Paris (2006-2012); Directeur du Département d’immunologie de l’Institut Pasteur, Paris (2006-2010); Chef de laboratoire à l’Institut Pasteur, Paris (2008-2012); Directeur de recherche de classe exceptionnelle at Inserm (Since 2010).

Since 2012: Emeritus scientist. Chercheur invité at Institut Pasteur, Paris (since 2012); Chercheur émérite at the Centre d'Immunologie de Marseille-Luminy (CIML), Marseille (since 2012); Membre associé at the Institut d’histoire et de philosophie des sciences et des techniques (IHPST), Paris (since 2015).

Scientific publications: https://scholar.google.ca/citations?user=RtPvxiwAAAAJ&hl=en&citsig=AMstHGRbj39MQsuKVIEzeRJiYh7-961Y1g

Books for a wide audience:

- Eric Vivier & Marc Daëron, L’Immunothérapie des cancers. Histoire d’une révolution médicale, Ed. Odile Jacob, Paris 2019

- Marc Daëron, L’immunité, la vie. Pour une autre immunologie. Ed. Odile Jacob, Paris 2021.

Scientific summary

Fc Receptors or the molecular bases of antibody functions in health and disease

Antibodies alone have no biological activities. They “recognize” antigens by their Fab portions, but in most cases, this has no biological consequence. To act on antigens, antibodies must associate with effectors systems by their Fc portion. These are complement components and cells that express receptors for the Fc portion of antibodies (FcRs). When binding to FcRs, antibodies endow cells devoid of antigen-recognition structures with bona fide antigen receptors. They enroll FcR-expressing cells, most or which belong to the myeloid lineage, in adaptive immunity. This determines the outcome of all antibody-dependent reactions, whether protective (e.g. in infection or cancer), pathogenic (e.g. in allergy or autoimmunity) or therapeutic (e.g. in vaccines and antibody-based immunotherapy). I have been studying FcRs since I began working in science. My main contributions are as follows:

1) Identification and functional characterization of murine and human FcRs: Identification (JI 1990, EJI 1991, JI 1996) and biologic activities of FcRs in vitro (JI 1992, 1994) and in vivo (Immunity 1996); Demonstration that the low-affinity IgG receptors FcRIIB inhibit cell activation induced by immunoreceptors (JCI 1995) and cell proliferation induced by RTKs (JI 1999); Dissection of mechanisms by which the transmembrane adapters LAT and NTAL regulate IgE receptor signaling (JI 2004, 2008); Demonstration that an IgG receptor, FcRIV, is a murine equivalent of IgE receptors expressed by human macrophages (JCI 2008); Establishment of the specificity and affinity of all human FcRs and their polymorphic variants for the four human IgG subclasses (Blood 2009).

2) Molecular mechanisms accounting for FcR functions: Dissection of biologically active FcR intracytoplasmic sequences (JI 1992, 1994); Description of the first Immunoreceptor Tyrosine-based Inhibition Motif (ITIM) in the intracytoplasmic domain of FcRIIB (Immunity 1995); Molecular definition of ITIMs shared by numerous inhibitory receptors (JBC 1997, JI 1999), and understanding that cell activation results from the transient displacement of an active balance between positive and negative signals, generated by Immunoreceptor Tyrosine-based Activation Motifs (ITAMs)- and ITIM-containing receptors; Analysis of molecular mechanisms by which the FcRIIB ITIM is phosphorylated (JI 1998) and recruits selectively the SH2 domain-containing isositol phosphatase SHIP1 (JBC 2000, 2001, 2004); Study of mechanisms used by SHIP1 to negatively regulate the various intracellular activation pathways (Immunity 2000, JBC 2001, JI 2005, Adv. Immunol. 2006); Phylogenetic analysis of ITIMs and identification of 300 potential ITIM-containing molecules encoded by human genes (Immunol. Rev. 2008). Discovery that FcRIIB can induce a reversible cell anergy which might provide the basis for a “universal” desensitization of allergic patients (Science Signal. 2016).

3) FcRs and FcR-expressing cells in human disease: Contribution of FcRIV in a murine model of rheumatoid arthritis (Cutting Edge, JI 2010); Discovery that probiotics inhibit the effector phase of antibody-induced inflammation (JI 2011*); Discovery that neutrophils are major players in systemic anaphylaxis (J. Clin. Invest. 2011*); Generation of humanized mice expressing human FcRs; Demonstration that the human IgG receptor FcRIIA triggers anaphylaxis and lung inflammation (Blood 2012); Demonstration that IgG receptors function as an inhibitory module that prevents IgG-dependent and controls IgE-dependent human basophil activation (J. Immunol. 2012); Demonstration that basophils from allergic patients are neither hyperresponsive to activation signals nor hyporesponsive to inhibition signals (JACI 2018). FcR-expressing innate cells in cancer therapy (Nature 2019). *Rated Top 2% by Faculty of 1000.