Le mardi 17 mars 2026, Monsieur Pierre ADAM, titulaire d'un Master en Sciences biomédicales à finalité approfondie et d’un Certificat de formation à la recherche en sciences biomédicales et pharmaceutiques, présentera l'examen en vue de l'obtention du grade de Doctorat en sciences biomédicales et pharmaceutiques, sous la direction de Monsieur Edouard LOUIS et de Madame Marie-Alice MEUWIS.

Cette épreuve consistera en la défense publique d'une thèse intitulée : "Molecular players of early epithelial transformation in colorectal carcinogenesis: insights from serrated and conventional adenoma pathways". 

Le jury sera composé de :

Philippe DELVENNE (Président), Ingrid STRUMAN (Secrétaire), Elisabeth LETELLIER (Univ. Luxembourg), Edouard LOUIS, Marie-Alice MEUWIS, Olivier PEULEN, Brieuc SAUTOIS, Sabine TEPJAER (KUL).

Résumé de la thèse

Colorectal cancer (CRC) develops through at least two main evolutionary routes: the conventional adenoma–carcinoma pathway, driven by chromosomal instability and APC/KRAS alterations, and the serrated pathway, characterized by a specific CpG island methylation phenotype, leading to microsatellite-instable cancers. Both arise from histologically and molecularly distinct premalignant lesions, whose underlying mechanisms remain incompletely characterized and functionally understood.

This thesis investigates key epithelial proteins involved in early colorectal neoplasia: S100A14 and NKCC1. We show that S100A14 is overexpressed in serrated precancerous lesions, where its expression correlates with enhanced lymphocytic infiltration, suggesting a role in shaping the immune microenvironment.

Conversely, we identify NKCC1 (SLC12A2), a Na⁺–K⁺–2Cl⁻ cotransporter, as a novel marker of intestinal stem cells that is upregulated in conventional adenomas. To investigate NKCC1’s role, we used patient-derived intestinal organoids and tumoroids. Functional studies in colorectal cell lines and organoid models demonstrate that NKCC1 inhibition dysregulates proliferative signaling, oxidative stress responses, and stemness-associated gene expressions, linking this ionic transporter to early tumor-initiating processes.

Together, these findings reveal distinct molecular key players implicated in the serrated and the conventional pathways of colorectal tumorigenesis and provide new insights into early epithelial transformation that may serve as early CRC biomarkers or therapeutic targets.