Intestinal stem cell biology
The gastrointestinal epithelium, one of the adult tissues with the highest self-renewing rates under steady-state conditions, constitutes an excellent model to better understand how adult stem cells contribute to tissue homeostasis, damage-induced regeneration processes or cancer.
We combine mouse studies and ex vivo organoid technology to investigate the molecular mechanisms involved in embryonic-to-adult transition, as well as regenerative and oncogenic-related processes in adults.
Molecular and cellular processes governing gut epithelium morphogenesis and regeneration
Our group has contributed to the developmental field by identifying and molecularly characterizing intestinal and gastric progenitors that line the prenatal epithelium surface before the emergence of the adult stem cells. We uncovered that adult regeneration in the stomach involves a dedifferentiation program during which terminally differentiated cells adopt a fetal-like progenitor transcriptomic profile to rebuild the damaged epithelium. The molecular mechanisms involved in such tissue plasticity remain to be fully dissected.
Physiological role of GPCRs in the gut epithelium
Stem cell markers
We study the function of two GPCR paralogs LGR4 and LGR5 in intestinal prenatal progenitors and adult stem cells. We have demonstrated that these receptors regulate progenitors and stem cell pools by modulating Wnt/β-catenin signaling and extracellular matrix synthesis, playing non-synonymous functions during development and under homeostasis.
Odorant receptors
We recently uncovered the role of the mouse olfactory receptor Olfr78 (human ortholog OR51E2), ectopically expressed in the colon. Through its activation by its natural ligand, the short chain fatty acid acetate, this GPCR contributes to colon homeostasis by promoting maturation of the serotonin-producing enterochromaffin cell subtype.
Whether these GPCRs are also involved in regulation of the tissue under pathological conditions remains to be explored.
Translational studies using organoid technology
Organoid technology offers promising potential for clinical applications toward personalized medicine.
In collaboration in the LGE-HUB, BEAMS and CHANI ULB labs, we have investigated the impact of cold atmospheric plasma, a proposed therapeutic innovative tool for biomedicine, and its potential selectivity on tumor versus normal organoids. We also investigate mechanisms associated with chemoresistance in colorectal cancer (collaboration with Institut Jules Bordet, BE).
In a preclinical study aimed at better understanding the gut/liver axis in the setting of Metabolic dysfunction-associated steatohepatitis (collaboration with LGE-HUB), our group has uncovered absorptive and barrier alterations in the duodenal epithelium from MASH patients using organoid technology. These findings pave the way for future drug screening assays to restore intestinal functionality.