Team Leader:

Mathias CHAMAILLARD

Contact

© Croix du Nord / Cécile Huyghe

Dr Chamaillard graduated his PhD in 2002 and has been appointed as a Research Director at Inserm in 2011 (H-index = 32 and 11,447 times cited without self-citations). At the Fondation Jean Dausset, he pionnered our understanding of the underlying mechanisms that are predisposing to inflammmatory bowel diseases by contributing to the identification of NOD2 as the major Crohn's disease predisposing gene (Nature 2001) and then moved to the laboratory of Professor Gabriel Nunez at the University of Michigan to further elucidate the function of the NOD2 gene (EMBO J 2003 and Science 2005) and of its closest related molecule NOD1 (Nature Immunology 2003). Dr Chamaillard received several awards, including the Crohn's and Colitis Foundation of America Young Investigator Award in 2004 and the UEP Top Abstract Prize, and he has has been invited to several international meetings, including Keystone symposium, FALK symposium, European Immunology Group Meeting and International Congress of Mucosal Immunology.

The cover image shows a section of human small intestine stained to reveal the presence of DNGR-1+ dendritic cells in lamina propria (red). These cells coexpress CD11c (purple) and HLA-DR (green). See the article by Poulin et al Blood 2012.

 

The Chamaillard's laboratory on Nods-like receptors in infection and immunity is interested in defining how Nods-like receptors contribute to microbial tolerance, host defence and antitumoral immunity, and how deregulation of several Nods-like receptors (including the Crohn's disease predisposing NOD2 gene) break down in Crohn's disease and colitis-associated colorectal cancer. Crohn's disease affects millions of individuals worldwide through the influence of several genetic and environmental factors. While a disproportionate immune response is found in Crohn's disease patients, our most recent studies in mice experimentally demonstrated that defects in the Crohn's disease predisposing NOD2 gene alters the functionality of the gut microbiome in a manner that it confers a risk of colitis and intestinal tumorigenesis (PMID:23281400). This led us to reveal an unexpected interplay with cigarette smoking that may modulate risk of developping Crohn's disease (PMID:28506689) and an impact on anti-cancer drugs efficacy as an epithelial-operating immune checkpoint (PMID: 27717798). More recently, we recently provided evidence that NLRP12 mediated proteosomal degradation of NOD2 in monocytes promotes bacterial tolerance and colonisation in a model of enteric infection (Nat Commun in press).

Using a variety of techniques and complex genetic models, we have contributed to the field of mucosal immunology by identifying novel dendritic cell subsets and several pathways that underlie inflammation-driven carcinogenesis. Notably, Lionel F. Poulin contributed to a better understanding of mouse and human dendritic cells by the identification and characterization of a novel subset of dendritic cells that is involved in the generation of cytotoxic CD8+ T cells in mice and human (PMID:18086861, 20038600 et 20479117). Encouraged by these results, our most recent work paid off by the identification of two additional regulatory pathways of NOD2 signalling that are required for the development of monocyte-derived dendritic cells (Chauvin et al., manuscript in preparation and PMID:29209091). Meanwhile, the laboratory has also unveiled several mechanisms that are contributing to the efficacy of the wound healing process (PMID:21593405, 27371534), among which the Nod-like receptor pyrin domain-containing protein 6 that we found to be required for regulating the gut microbiota (PMID:29139477) and intracellular detection of lipoteichoic acid (PMID:30392956).

The Chamaillard's laboratory was created in 2010 with the highest possible grade (A+) by the French national research assessment agency and with an uninterrupted funding record since 2004. During the last five years, our laboratory was labelled as Equipe Fondation pour la Recherche Médicale. Since then, about 80 papers were published in peer-reviewed international journals in the field of immunology, gastroenterology and oncology, which includes about 20 cutting-edges original articles (eg. Blood Gastroenterology, Gut, Immunity, J Clin Invest, J Exp Med, Nature Medicine, Proc Natl Acad Sci U S A, Science).