Biomedical research institute
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    Intestinal Self-Renewal and Tumorigenesis

    Team leader

    The major objective of our team is to understand the molecular mechanisms controlling intestinal homeostasis and to determine how these cellular functions can be subverted during malignant transformation. Our main approaches are based on the use of genetically-engineered mouse models, intestinal organoids and human tumor samples.

    Research interests

    The mechanisms underlying intestinal homeostasis are of fundamental biological importance and have critical implications for colorectal cancer. Our projects focus on the factors involved in the self-renewal of the intestinal epithelium and the mechanisms associated with intestinal carcinogenesis. For many years, we investigated the involvement of Wnt/β-catenin signaling as a major player in intestinal cell turnover and the emergence of colorectal cancer.
    Our goal is to identify the factors involved in the maintenance and renewal of normal intestinal stem cells and understand the early changes associated with intestinal neoplasia to identify new markers of disease and new therapeutic targets. Our current projects are to continue and expand our research by studying the intrinsic factors expressed in intestinal stem cells as well as the microenvironmental factors involved in intestinal homeostasis and tumorigenesis.
    We are currently studying with novel inducible mouse models the impact of diet, gut microbiota, host immune system on intestinal homeostasis and in Wnt-driven tumor development. From a translational research point of view, collaboration with the gastroenterology and digestive oncology departments of the Cochin University Hospital as well as the pathology department has been set up. This allows us to better understand clinical issues and develop fundamental biology research projects in line with clinicians' expectations.

    Main publications

    Senni N, Savall M, Cabrerizo Granados D, Alves-Guerra MC, Sartor C, Lagoutte I, Gougelet A, Terris B, Gilgenkrantz H, Perret C, Colnot S, Bossard P. b-Catenin-Activated Hepatocellular carcinomas are addicted to fatty acids. Gut. 2019; 68(2):322-334

    Abitbol S, Dahmani R, Coulouarn C, Ragazzon B, Mlecnik B, Senni N, Savall M, Bossard P, Sohier P, Drouet V, Tournier E, Dumont F, Sanson R, Calderaro J, Zucman-Rossi J, Vasseur-Cognet M, Just PA, Terris B, Perret C, Gilgenkrantz H. AXIN deficiency in human and mouse hepatocytes induced hepatocellular carcinoma in the absence of b-catenin activation. J Hepatol. 2018;68(6):1203-1213

    Levy J, Cacheux W, Bara MA, L'Hermitte A, Lepage P, Fraudeau M, Trentesaux C, Lemarchand J, Durand A, Crain AM, Marchiol C, Renault G, Dumont F, Letourneur F, Delacre M, Schmitt A, Terris B, Perret C, Chamaillard M, Couty JP, Romagnolo B. Intestinal inhibition of Atg7 prevents tumour initiation through a microbiome-influenced immune response and suppresses tumour growth. Nat Cell Biol 2015;17 (8):1062-73

    Coriat R, Alexandre J, Nicco C, Quinquis L, Benoit E, Chéreau C, Lemaréchal H, Mir O, Borderie D, Tréluyer JM, Weill B, Coste J, Goldwasser F, Batteux F. Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir.  Journal of Clinical Investigation 2014; 124 (1): 262-72

    Durand A, Donahue B, Peignon G, Letourneur F, Cagnard N, Slomianny C, Perret C, Shroyer NF, Romagnolo B. Functional intestinal stem cells after Paneth cell ablation induced by the loss of transcription factor Math1 (Atoh1). Proc Natl Acad Sci U S A 2012;109(23):8965-70

    Peignon G, Durand A, Cacheux W, Ayrault O, Terris B, Laurent-Puig P, Shroyer NF, Van Seuningen I, Honjo T, Perret C, Romagnolo B. Complex interplay between beta-catenin signalling and Notch effectors in intestinal tumorigenesis. Gut 2011;60(2):166-76

    Andreu P, Peignon G, Slomianny C, Taketo MM, Colnot S, Robine S, Lamarque D, Laurent-Puig P, Perret C, Romagnolo B. A genetic study of the role of the Wnt/beta-catenin signalling in Paneth cell differentiation. Dev Biol 2008;324(2):288-96

    Andreu P, Colnot S, Godard C, Laurent-Puig P, Lamarque D, Kahn A, Perret C, Romagnolo B. Identification of the IFITM Family as a New Molecular Marker in Human Colorectal Tumors. Cancer Res 2006;66(4):1949-1955