TEAM 1 - GUT PROTEASE SIGNAL
Responsables : 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.
Key Words
Intestinal Mucosa - Proteolytic Homeostasis - Intestinal Pathologies - Organoids - Visceral hypersensitivity

Members

Past Members

Tools & 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

  • Modelling postoperative pathologic ileus in mice: a simplified and translational approach.
    Neurogastroenterology and Motility.




  • Intestinal organoids in farm animals.
    Beaumont M, Blanc F, Cherbuy C, Egidy G, Giuffra E, Lacroix-Lamandé S, Wiedemann A.Vet Res. 2021 Feb 25;52(1):33. doi: 10.1186/s13567-021-00909-x.PMID: 33632315 Free PMC article. Review.


             
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