TEAM 1 PATHOPHYSIOLOGY OF THE INTESTINAL  EPITHELIUM

  • Intestinal mucosa
  • Proteolitic balance
  • intestinal pathologies
  • Organoids

Nathalie Vergnolle

Team Leader

RESEARCH DESCRIPTION

Pathophysiology of the intestinal epithelium

The overall goal of the team "Pathophysiology of the intestinal epithelium" 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 (CRC) and infections.The research team has expertise on the biology of the intestinal mucosa and in particular its barrier functions, secretory functions, absorptive functions, regeneration as well as host-microbiota/pathogen interaction and neurally-controlled sensory, secretory and motility functions. The roles of the proteolytic balance of the mucosa in the intestinal physiology and pathologies are more particularly studied. Some proteases have been shown to be dysregulated in different pathophysiological contexts and are now deeply studied in order to clarify their functions in pathogenesis.
 The implication of protease-activated receptors (PARs) in digestive pathologies is an important axis of investigations in our team. Another point of view developed by our team is how gender may influence pathologies generated by alterations in the intestinal crypt. Finally, the team is also interested in the immunity-mediated dialogue between colic primary tumor and metastasis. Important links with private companies are established in order to develop therapeutic molecules against the pathophysiology – associated proteases.

​Part of the team has emerged as  an independent research group entitled "Interaction between the environment and the intestinal epithelium" under the co-direction of Audrey Ferrand and Frederik Barreau.

Members 

FORMER  MEMBERS

ANIMAL AND CELLULAR MODELS / METHODS

  • ​​Human and murine organoid models : Organoids recreate in vitro and in 3 dimensions, an intestinal epithelial monolayer, gathering all the diversity of intestinal epithelial cells and preserving the architecture. Such in vitro models are powerful tools for fundamental research in intestine (patho)physiology and for therapeutic development.
  •  Cell lines of human and murine epithelial cells.
  • In vitro and in vivo evaluating the barrier function of the epithelium.
  • Animal models of chronic inflammatory bowel disease.
  • Parasitic or bacterial infection models.
  • Animal models of visceral hypersensitivity.
  • Animal models of colorectal cancer.
  • Protease biochemistry: Production, activity assay, profiling using activity-based probes.
  • Protease-activated receptors (PARs): KO mice, transgenic cell lines, crispr-cas cell lines, pharmacological inhibitors.

PUBLICATIONS (FROM 2017)

  • Vergnolle, N. & Cirillo, C. Neurons and Glia in the Enteric Nervous System and Epithelial Barrier Function. Physiology (Bethesda) 33, 269-280, doi:10.1152/physiol.00009.2018 (2018). I.F. 4.86
  • Sebert, M., Denadai-Souza, A., Quaranta, M., Racaud-Sultan, C., Chabot, S., Lluel, P., Monjotin, N., Alric, L., Portier, G., Kirzin, S., Bonnet, D., Ferrand, A. & Vergnolle, N. Thrombin modifies growth, proliferation and apoptosis of human colon organoids: a protease-activated receptor 1- and protease-activated receptor 4-dependent mechanism. Br J Pharmacol 175, 3656-3668, doi:10.1111/bph.14430 (2018)
  • Desormeaux, C., Bautzova, T., Garcia-Caraballo, S., Rolland, C., Barbaro, M. R., Brierley, S. M., Barbara, G., Vergnolle, N. & Cenac, N. Protease-activated receptor 1 is implicated in irritable bowel syndrome mediators-induced signaling to thoracic human sensory neurons. Pain 159, 1257-1267, doi:10.1097/j.pain.0000000000001208 (2018). I.F. 5.56
  • Denadai-Souza, A., Bonnart, C., Tapias, N. S., Marcellin, M., Gilmore, B., Alric, L., Bonnet, D., Burlet-Schiltz, O., Hollenberg, M. D., Vergnolle, N. & Deraison, C. Functional Proteomic Profiling of Secreted Serine Proteases in Health and Inflammatory Bowel Disease. Sci Rep 8, 7834, doi:10.1038/s41598-018-26282-y (2018). I.F. 4.12
  • Rolland-Fourcade, C., Denadai-Souza, A., Cirillo, C., Lopez, C., Jaramillo, J. O., Desormeaux, C., Cenac, N., Motta, J. P., Larauche, M., Tache, Y., Berghe, P. V., Neunlist, M., Coron, E., Kirzin, S., Portier, G., Bonnet, D., Alric, L., Vanner, S., Deraison, C. & Vergnolle, N. Epithelial expression and function of trypsin-3 in irritable bowel syndrome. Gut 66, 1767-1778, doi:10.1136/gutjnl-2016-312094 (2017). I.F. 17.02
  • Denadai-Souza, A., Ribeiro, C. M., Rolland, C., Thouard, A., Deraison, C., Scavone, C., Gonzalez-Dunia, D., Vergnolle, N. & Avellar, M. C. W. Effect of tryptase inhibition on joint inflammation: a pharmacological and lentivirus-mediated gene transfer study. Arthritis Res Ther 19, 124, doi:10.1186/s13075-017-1326-9 (2017). I.F. 4.27
  • Bonnart, C., Feuillet, G., Vasseur, V., Cenac, N., Vergnolle, N. & Blanchard, N. Protease-activated receptor 2 contributes to Toxoplasma gondii-mediated gut inflammation. Parasite Immunol 39, doi:10.1111/pim.12489 (2017). I.F. 2.84
  • Nasri I, Chawech R, Girardi C, Mas E, Ferrand A, Vergnolle N, Fabre N, Mezghani-Jarraya R, Racaud-Sultan C. 2017. Anti-inflammatory and anticancer effects of flavonol glycosides from Diplotaxis harra through GSK3β regulation in intestinal cells. Pharm Biol. 2017 Dec;55(1):124-131. 
​