Fabrice LAURENT

Information

Scientific interests and projects

General scientific interests: Apicomplexa and Mucosal Immunity (AIM) team is working on two apicomplexan parasites with intestinal tropism, Cryptosporidium and Eimeria. Historically our research on cryptosporidiosis mainly concerned investigations on the protective and pathological immune responses. However, we extend our researches and recently start to characterize the molecular mechanisms that govern Cryptosporidium/intestinal epithelial cell interactions and the long term consequences of the infection on intestinal homeostasis and immune disorders. In man and farm animals, cryptosporidiosis is poorly controlled and we wish to combine two complementary strategies for an efficient control of the disease. Based on strong dependence of functional immune responses for controlling Cryptosporidium we wish to develop immunostimulatory strategies dedicated to neonates in order to strengthen their ability to limit parasite growth. Drug therapies are limited both in human and livestock, we therefore aim to develop new potent molecules to control parasite development.

Scientific activities to be developed in the framework of Parafrap:
I-Virulence factors: Thanks to transgenesis now available in the laboratory we wish to identify cryptosporidium virulence factors that co-opt specific host-epithelial cell signaling pathways upon invasion and development.

II- Gut physiopathology: Infection of young individuals by C. parvum induces a long-term defect on intestinal gut physiology and this has been linked to the occurrence of Irritable Bowel Syndrome (IBS). We plan to investigate the contribution of Paneth cells (PC) and their antimicrobial peptides on the onset of this intestinal disorder.

III- Control strategies: In collaboration with several international teams including Ali Hakimi’s team from Parafrap with whom we recently identified a first promising target (CPSF3) we wish to further develop our therapeutic arsenal against Cryptosporidium, from drug screening to molecular target identification and in vivo final validation (rodent and large animal models).

Top 5 publications of the last 5 years

1. Diaz-Martin S, Swale C, Bellini V, Dobrescu I, Wenker J, Brenier-Pinchart MP, Braun L, Tollec A, Corrao C, Couté Y, Mas C, Laurent F, Bowler M, Hakimi MA, Bougdour A. Structural and functional characterization of TgGSK3, a druggable kinase in Toxoplasma gondii. Nat Commun. 2025 Nov 5;16(1):9765. doi: 10.1038/s41467-025-64701-7.PMID: 41193440

2. Fernandez M, Pezier T, Pichon J, Vern YL, Werts C, Lacroix-Lamandé S. Administration of the NOD2 Agonist MDP Reduces Cryptosporidium parvum Infection in Neonatal Mice Through IL-22 Involvement. Eur J Immunol. 2025 Oct;55(10):e70080. doi: 10.1002/eji.70080.

3. Baillou A, Tomal F, Chaumeil T, Barc C, Levern Y, Sausset A, Pezier T, Schulthess J, Peltier-Pain P, Laurent F, Lacroix-Lamandé S. Characterization of intestinal mononuclear phagocyte subsets in young ruminants at homeostasis and during Cryptosporidium parvum infection. Front Immunol. 2024 May 2;15:1379798. doi: 10.3389/fimmu.2024.1379798. eCollection 2024.PMID: 38756777

4. Tomal F, Sadrin G, Gaboriaud P, Guitton E, Sedano L, Lallier N, Rossignol C, Larcher T, Rouille E, Ledevin M, Guabiraba R, Silvestre A, Lacroix-Lamandé S, Schouler C, Laurent F, Bussière FI. The caecal microbiota promotes the acute inflammatory response and the loss of the intestinal barrier integrity during severe Eimeria tenella infection. Front Cell Infect Microbiol. 2023 Aug 23;13:1250080. doi: 10.3389/fcimb.2023.1250080. eCollection 2023.PMID: 37680750

5. Ribeiro E Silva A, Diallo MA, Sausset A, Robert T, Bach S, Bussière FI, Laurent F, Lacroix-Lamandé S, Silvestre A. Overexpression of Eimeria tenella Rhoptry Kinase 2 Induces Early Production of Schizonts. Microbiol Spectr. 2023 Aug 17;11(4):e0013723. doi: 10.1128/spectrum.00137-23. Epub 2023 Jun 1.PMID: 37260371