Gut Protease Signals
Team 1
Research Programs
The general objective of the “Gut Protease Signals” team is to understand the mechanisms of diseases associated with dysfunctions of the intestinal epithelium: chronic inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), colorectal cancer, and infections. The research team has expertise in intestinal mucosa biology, particularly in its barrier functions, secretory functions, absorption, regeneration, the neuronal control of secretion and motility, intestinal nociception and visceral pain, as well as the interaction between host/microbiota/pathogens.
The role of mucosal proteolytic balance in intestinal physiology and pathologies is a key focus of study. Certain proteolytic activities have been shown to be deregulated in various pathophysiological contexts, and these proteases are now being thoroughly investigated to clarify their roles in pathogenesis. The involvement of protease-activated receptors (PARs) in digestive pathologies is an historical and major line of investigation for the team.
Additionally, our team is interested in how gender and age may influence pathologies arising from alterations in the intestinal crypt. Pain associated with the intestinal organ is also a major focus of the team, which investigates mechanisms of visceral hypersensitivity, in order to propose new therapeutic options for the treatment of visceral pain and discomfort. A focus on the relationship between epithelial, immune and microbial mediators in mediating nociceptive signals is proposed, in an attempt to understand the complexity of peripheral signals involved in acute and chronic pain signaling in the gut.
Strong partnerships have been established with pharmaceutical industry to develop therapeutic molecules targeting mediators identified for their pathogenic role in intestinal pathologies.
People
Tools and models
- Human and Murine Organoid Models: Organoids allow for the in vitro, three-dimensional recreation of an intestinal epithelial monolayer, encompassing the full diversity of intestinal epithelial cells while preserving tissue architecture. These in vitro models are powerful tools for fundamental research in intestinal physiology and pathophysiology, as well as for therapeutic development. We run organoid models from colon and small intestine, from healthy controls or patient’s tissues, in 3-dimensions and in transwells (interfaced organoid cultures with microbiota and immune cells).
- Human and murine intestinal epithelial cell lines
- In vitro and in vivo evaluation of intestinal epithelial barrier function
- Animal models of chronic inflammatory bowel disease (DSS, TNBS, oxazolone)
- Animal models of Irritable Bowel Syndrome (patient’s tissues-derived, stress, post-infectious)
- Bacterial infection models (Salmonella, Pseudomonas)
- Biofilm culture models and gut microbiota studies
- Animal models of visceral hypersensitivity, visceral pain measures
- Animal models of colorectal cancer
- Postoperative ileus models
- Protease biochemistry: production, measurement of proteolytic activity, activity-based probe profiling
- Protease-Activated Receptors (PARs): knockout mice, transgenic cell lines, CRISPR-Cas9-modified cell lines, pharmacological antagonists
- Transgenic mice overexpressing proteases (Elastase, Trypsin-3), and mice deficient for some protease expression.
Publications
Human fallopian tube organoids provide a favourable environment for sperm motility. Nicolas Gatimel, G. Perez, ..., Céline Deraison, Jean‐Paul Motta, ..., Nathalie Vergnolle, Human Reproduction 2025. DOI: 10.1093/humrep/deae258
S. aureus drives itch and scratch-induced skin damage through a V8 protease-PAR1 axis. Liwen Deng, Flavia G. Costa, ..., Céline Deraison, ..., Nathalie Vergnolle, et al., Cell 2023. DOI: 10.1016/j.cell.2023.10.019
Effects of Hydrogen Sulfide on the Microbiome: From Toxicity to Therapy. André G. Buret, Thibault Allain, Jean‐Paul Motta, et al., Antioxidants & Redox Signaling 2021. DOI: 10.1089/ars.2021.0004
Gastrointestinal biofilms in health and disease. Jean‐Paul Motta, John L. Wallace, ..., Céline Deraison, Nathalie Vergnolle, Nature Reviews Gastroenterology & Hepatology 2021. DOI: 10.1038/s41575-020-00397-y
Characterization of Human Colon Organoids From Inflammatory Bowel Disease Patients. Emilie d'Aldebert, Muriel Quaranta, ..., Claire Racaud‐Sultan, Emmanuel Mas, Céline Deraison, Nathalie Vergnolle, Frontiers in Cell and Developmental Biology 2020. DOI: 10.3389/fcell.2020.00363
Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2. Alberto Caminero, Justin L. McCarville, ..., Céline Deraison, ..., Nathalie Vergnolle, et al., Nature Communications 2019. DOI: 10.1038/s41467-019-09037-9
House dust mites activate nociceptor–mast cell clusters to drive type 2 skin inflammation. Nadine Serhan, Lilian Basso, ..., Chrystelle Bonnart, et al., Nature Immunology 2019. DOI: 10.1038/s41590-019-0493-z
Protectin D1 n-3 DPA and resolvin D5 n-3 DPA are effectors of intestinal protection. Thomas Gobbetti, Jesmond Dalli, ..., Nathalie Vergnolle, Céline Deraison, et al., Proceedings of the National Academy of Sciences 2017. DOI: 10.1073/pnas.1617290114
Epithelial expression and function of trypsin-3 in irritable bowel syndrome. Claire Rolland-Fourcade, Alexandre Denadai‐Souza, ..., Jean‐Paul Motta, ..., Céline Deraison, Nathalie Vergnolle, Gut 2017. DOI: 10.1136/gutjnl-2016-312094
Giardia duodenalis induces pathogenic dysbiosis of human intestinal microbiota biofilms. Jennifer Beatty, Sarah Akierman, Jean‐Paul Motta, et al., International Journal for Parasitology 2017. DOI: 10.1016/j.ijpara.2016.11.010
The Intestinal Microenvironment and Functional Gastrointestinal Disorders. Giovanni Barbara, Christine Feinle‐Bisset, ..., Nathalie Vergnolle, et al., Gastroenterology 2016. DOI: 10.1053/j.gastro.2016.02.028
