Harry SokolCentre de recherche scientifique Saint-Antoine (CRSA) - Inserm / Sorbonne Université
Mes recherches
Harry Sokol, is Professor in the Gastroenterology department of the Saint Antoine Hospital (APHP, Paris, France) and is the head of the Gut Microbiota and Immunity lab (INSERM CRSA UMRS 938, Sorbonne Université, Paris). Harry Sokol is an internationally recognized expert in Inflammatory Bowel Disease (IBD) and in gut microbiota fields. He published over 180 papers on these topics in major journals (including Gut, Gastroenterology, Cell Metabolism, Cell Host & Microbe, Nature communication, Nature Medicine). His work on the role of the gut microbiota in IBD pathogenesis led to landmark papers describing the IBD-associated dysbiosis (imbalance in gut microbiota composition) and the role of the pivotal commensal bacteria Faecalibacterium prausnitzii in gut homeostasis and in IBD. Currently, his work focuses on deciphering the gut microbiota-host interactions in health and diseases (particularly IBD), in order to better understand their role in pathogenesis and develop innovative treatments. Harry Sokol is exploring particularly the role of the microbiota in tryptophan metabolism for which he is recipient of an ERC grant. Beside basic science, he is also involved in translational research. He is the current president of the French group of fecal microbiota transplantation, he coordinated a pilot randomized control trial evaluating fecal microbiota transplantation in Crohn’s disease and he is currently coordinating a phase III nationwide randomized control trial evaluating fecal microbiota transplantation in ulcerative colitis.
Mon projet ATIP-Avenir
Role of Card9 in intestinal homeostasis
The gastrointestinal (GI) tract is a complex milieu in which coexist host cells, a wide array of microorganisms and food antigens. The GI microbiota is strikingly well tolerated by the host. The mechanisms involved in this homeostasis remain unclear. The exact pathogeny of inflammatory bowel disease (IBD) is still unknown but involves a dysregulated immune response to the GI microbiota in genetically predisposed host. In IBD a deviation of the GI microbiota composition (dysbiosis) has been pointed out. Concomitantly, genetic studies have identified several susceptibility loci in genes involved in the interaction with microorganisms, such as Card9 (Caspase Recruitment Domain 9). Card9 is an adapter protein playing a central role for the integration of signals downstream of Pattern recognition receptors. However its role in the GI immunity has not been investigated yet. The aim of this proposal is to decipher the role of Card9 in GI homeostasis in health and in IBD pathogenesis using an integrated “microbiome/immunology” approach.
Here are the 4 tasks we propose:
Task 1: GI Microorganisms and Pathogen-associated molecular patterns sensing requiring Card9: In vitro screen
We will assess which microbial component of the GI microbiota may signal via Card9 in macrophages and dendritic cells.
Task 2: Role of Card9 in shaping the GI immune system
We will investigate the effect of microbial stimuli known to have a Card9-dependant signalling (Based on literature and on results of Task 1) on the GI immunity. For this purpose, we will use WT and Card9 KO germ-free mice.
Task 3: Role of Card9 in GI Microbiota Regulation
We will analyze the GI microbiota composition of WT and Card9 KO mice in steady state and in DSS-elicited colitis context. We will also analyze the host intestinal response using microarray technology.
Task 4: Application in Crohn’s disease patients
We will validate our in vitro and mouse finding in human Crohn’s disease patients genotyped for Card9 SNP.
Harry Sokol est également lauréat ERC Starting Grants 2016