Michelina Plateroti

University of Strasbourg – U1113 – INSERM – IRFAC

France

Telephone: +33 03 88 27 53 56

Personal webpage: here

Main areas of expertise: Development; Cancer; Stem cells

♦ Signaling networks and intestinal epithelium progenitor/stem cell physiopathology

The peculiarity of the gastrointestinal epithelium is the presence of a proliferative compartment, where are located multipotent stem cells and progenitors which proliferate and are engaged in differentiation toward multiple lineages. Several signaling pathways are involved in the control of the perpetual cell proliferation and differentiation of the stem and progenitor cells. The most accepted hypothesis is that these same pathways, once deregulated, are responsible for the initiation and/or the tumor progression. Moreover, it is clear that gut tumorigenesis and tumor progression result from multiple and sequential alterations in the expression of key genes. Our laboratory is studying since several years the importance of the thyroid hormone signaling through its nuclear receptor TRα1 in intestinal development, homeostasis and tumorigenesis. In particular, data have shown that TRα1 controls the epithelial progenitor proliferation via the regulation of key genes of the Wnt, BMP and Notch pathways, all involved in progenitor/stem cell physiopathology. A recent study demonstrated that the first event of the intestinal tumorigenesis involves the transformation of the physiological stem cells. However, the signaling pathways directly involved in the biology of the physiological and cancer stem cells, i.e. self-renewal and multi-potency, have not been identified yet.

Within this general line of research, specific projects include:

Characterization of the mechanisms involved in the control of normal and pathological crypt cell proliferation dependent on multiple signals
Study of these same signals at the level of the gut stem cells
Relevance of these studies on human colorectal cancer

The studies use mouse models generated and/or available in our laboratory. Experimental approaches include cellular and molecular biology in in vivo and ex vivo models.

Key publications:

Cambuli FM, Rezza A, Nadjar J, Plateroti M (2013) Musashi1-eGFP mice, a new tool for differential isolation of the intestinal stem cell populations. Stem Cells, doi: 10.1002/stem.1428

Sirakov M, Skah M, Nadjar J, Plateroti M (2013) Thyroid hormone’s action on progenitor/stem cell biology: new challenge for a classic hormone? Biochim Biophys Acta 1830: 3917-3927

Sirakov M, Skah S, Lone I, Nadjar J, Angelov D, Plateroti M (2012) Multi-level interactions between the nuclear receptor TRα1 and the WNT effectors β-catenin/Tcf4 in the intestinal epithelium. PLoS One 7: e34162

Rezza A, Skah S, Roche C, Nadjar J, Samarut J, Plateroti M (2010) The overexpression of the putative gut stem cell marker Musashi1 induces tumorigenesis through Wnt and Notch activation. J Cell Sci 123: 3256-3265

Kress E, Skah S, Sirakov M, Nadjar J, Gadot N, Scoazec JY, Samarut J, Plateroti M (2010) Cooperation between the thyroid hormone receptor TRα1 and the WNT pathway in the induction of intestinal tumorigenesis. Gastroenterology 138: 1863-1874

Kress E, Rezza A, Nadjar J, Samarut J, Plateroti M (2009) The Frizzled related sFRP2 gene is a target of the TRα1 thyroid hormone receptor and activates the β-catenin signaling in mouse intestine. J Biol Chem 284: 1234-1241