CV Science

Mathias Chamaillard Research director, Team leader, Principal Investigator, PhD

Course and current status

Current position

1. Head of the Laboratory Inflammasome and Ion Channels at Inserm UM1003
2. Deputy director of Inserm UMR1003

Course

Since 2011:  Team leader - Directeur de recherche Inserm

2008/10:    Junior tenure scientist – Chargé de recherche première classe - at Institut Pasteur de Lille in the research unit Inserm U801 headed by Pr. M. Simonet;

2005/08:    Postdoctoral research fellow then Junior tenure scientist – Chargé de recherché première classe - in the research unit Inserm U795 headed by Pr. P. Desreumaux;

2003/05:    Postdoctoral research fellow, University of Michigan, Ann Arbor, USA (Supervisor Pr. G. Nùñez);

1998/02:    Ph. D., Inserm U434, Paris, France (Supervisor Pr. G. Thomas);

1997:         Master degree, Inserm U347, Kremlin-Bicêtre, France (Supervisor Dr. M. Meunier-Rotival) and Jacques Monod Institute, Paris, France (Supervisor Pr. C. Lamour-Isnard);

1995:         Graduate, Tours’ Hospital, Tours, France (Supervisor Dr. S. Briault).

Scientific summary

Over the past five years, we had oriented our research program with an assumed choice to better understand the contribution of Crohn’s disease predisposing genes to immune surveillance to enteric infection and colorectal carcinogenesis. To this end, we invested time and efforts for acquiring complementary skills in bioinformatics with tools for microbiota and bulk RNA-seq analysis. We also contributed to the acquisition of a GMP-compliant MACSQuant® Tyto® Cell Sorter, a solution for western-based proteomic on single-cells (Milo®) and a micro droplet-based scRNA-seq that has been developed by the 10X Chromium. The implementation of the aforementioned equipments at ONCOLille aim at fostering our translational research programs with the Hospital-University campus of Lille and the Centre Oscar Lambret. Furthermore, the laboratory has implemented non-invasive imaging technologies for endoscopy and setup protocols of bone marrow chimera mice and of model of three-dimensional structures of cultured intestinal cells (PMID: 36350252). Using such variety of techniques and tools, this led us to address a number of important issues in an exponentially growing field by applying our two decades of knowledge on the pathophysiology of Crohn’s disease for studying the bidirectional communication between the microbiota and intestinal mucosa in response to cancer and infection. Our growing interactions with pharmaceutical laboratories (Mendes SA, Miyarisan Pharmaceuticals, Bioprox Healthcare, Imabiotech and HCS Pharma) will further leverage impact to patient care and public health.

1.      Control of resistance to colonization and bacterial tolerance by intestinal phagocytes. The research activities of our team unveiled that bacterial sensing through NOD2 in myeloid cells heightens their immunosuppressive properties (PMID: 37876927) and the clearance of enteropathogens (PMID: 37655966, 30279238 and 30559449 and a declaration of invention EP14306662). These results encouraged us to further understand NOD2 function in monocytes-derived phagocytes, which are particularly abundant throughout the connective tissue that underlies the intestinal epithelial cells. Our work revealed new molecular insights into how macrophage development from monocytes is negatively regulated by NOD2 signalling (PMID: 37415975). These findings led us to speculate that the deregulated functionality and influx of phagocytes in Crohn’s disease patients presumably result from an inappropriate development of their progenitors that may account for their protumoral effect. At the meantime, this contributed to molecular mechanism of mucosal protection in colitis, which are particularly relevant for our understanding of the pathogenesis of inflammatory bowel diseases (PMID: 29139477, PMID: 36175116 and PMID: 35917251). Meanwhile, we provided mechanistic conclusions on the means whereby NOD2 contributes to intestinal microbial community composition after antibiotic treatment (PMID: 32289499).

2.      Remote control of immune surveillance and resistance to anti-cancer drugs by the gut microbiota. Under these circumstances, our central hypothesis is that dysregulation of gut barrier function modulates immune surveillance and the efficacy of cancer treatments (such as radiation therapy and chemotherapies). To the best of our knowledge, our studies are pioneer in describing that Colibactin-Producing Escherichia coli (CoPEC) niches within the tumour microenvironment is responsible of immunosuppressive lipid overload facilitating colorectal cancer progression and chemoresistance (https://doi.org/10.1101/2023.03.13.523827). This discovery opened opportunities to further investigate new pathways in the course of the next mandate. On this note, we initiated a funded translational research program aiming at identifying easy-to-use microbiome-based biomarkers of the efficacy and toxicity of chemoradiotherapies. This effort led to an international patent application filed with Inserm Transfert for improving the resilience of the gut microbiota by the use of flavones (WO2017198847A1) and allowing a research contract with Miyarisan Pharmaceuticals. This cooperation provided experimental evidence that the biotherapeutic Clostridium butyricum MIYAIRI 588 strain potentiates enterotropism of Rorgt⁺Treg and immune checkpoint blockade (ICB) efficacy (Gut Microbes In press).

Microbiota-modulated type 3 immunity on tumorigenesis and resistance to immunotherapy. Our most recent work revealed that the epithelial response to toxins secreted by either ETBF or C. difficile is responsible of IL-17-driven carcinogenesis (PMID: 29398651, 35678528). This led us to discover that the protumoral properties of the biofilm that were enriched in CoPEC and ETBF (PMID:29420293). This was the first demonstration that invasive biofilms and their community of bacteria adhering the intestinal epithelium could represent risk factors of CRC through mechanisms closely related to chronic IL-17 colitis. Importantly, we found that whereas IL-17-associated colon tumorigenesis in ETBF-colonized Min^Apc/- was resistant to ICB, introduction of BRAF^V600E mutation to the colonic epithelium induced IFNg signature and response to anti-PD-L1. Meanwhile, in MSI and MSS CRC treated with pembrolizumab (NCT 01876511), we found that an intratumoral IL-17 signature was also associated with worst outcome (PMID:31061070). Given that it is not yet completely understood what are the origin of intratumoral IL-17, we herein propose to identify which bacteria are recognized by Th17 cells and to define the immunometabolic contexture of Il-17-inducing bacterial niches. To this end, we developed an assay (PCT/US2017/056557), which can identify bacterial antigens recognized by T cells and T cells detection within the tumour bed (PMID:29895573).