Nathalie Vergnolle

Céline Deraison

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

Nathalie Vergnolle
Researcher

Agnès Wiedemann
Researcher

Amandine Dupuis
Staff

Anissa Edir
Staff

Beatriz Hernandez-Suarez
Posdoc

Céline Deraison
Researcher

Chrystelle Bonnart
Researcher

Claire Racaud
Researcher

Corine Rolland
Staff

Etienne Buscail
PU-PH

Jean-Paul Motta
Researcher

Julie Thevenin
Staff

Laura Guiraud
Staff

Romain Gauthier
PhD Student

Sofia Faggin
Posdoc

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