The mechanisms that regulate intestinal homeostasis represent a major biological challenge and have critical implications for the development of colorectal cancer. Our team focuses on the factors controlling intestinal epithelial self-renewal and their role in intestinal carcinogenesis.
Over the past years, we have demonstrated the central role of the Wnt/β-catenin signaling pathway in intestinal cell renewal and the initiation of colorectal cancer. In particular, we have contributed to a better understanding of this pathway by developing a conditional mouse model of the Apc gene. Our work has shown that Wnt/β-catenin signaling is essential for the maintenance and self-renewal of intestinal stem cells, and that its constitutive activation following Apc loss promotes colorectal cancer development, highlighting the close link between intestinal stem cells and tumor cells.
We have also demonstrated that Wnt/β-catenin signaling contributes to the organization of the intestinal stem cell niche by inducing the differentiation of Paneth cells, which provide essential growth factors, including Wnt and Notch ligands. In addition, the surrounding mesenchyme represents a major source of signals required for stem cell maintenance. More recently, we identified the tumor suppressor role of the Axin1 gene, a known regulator of Wnt/β-catenin signaling, and demonstrated its anti-tumor function through the stimulation of immune surveillance.
We are also investigating the role of autophagy in the maintenance and renewal of normal intestinal stem cells, as well as its involvement in tumor development and host–pathogen interactions. Our current projects aim to further expand this work by characterizing various mouse models targeting macroautophagy and chaperone-mediated autophagy.
From a translational perspective, we have established close collaborations with the departments of gastroenterology, digestive oncology, and pathology at Cochin Hospital. This synergy allows us to better integrate clinical challenges and to align our fundamental research with the needs of clinicians.