Principal Investigator Jean Paul THIERY
Jean Paul Thiery obtained his PhD from the University of Paris. He did his postdoctoral studies at the Rockefeller University, New York. In 1978, he established his research group at the Developmental Biology Institute of the CNRS in Paris. He became the head of a CNRS laboratory at the Ecole Normale Superieure in 1987 and joined the Institut Curie in 1995. His expertise was recognized by his appointment as the inaugural Director of the Department of Translational Research in Cancer at the Institut Curie in 2003. Professor Jean Paul Thiery joined IMCB in October 2006. He currently holds dual appointments as Deputy Director at IMCB and Chief Scientific Officer of Experimental Therapeutics Centre.

Assistant Professor Jacqueline VELTMAAT, PhD

The epithelial cell has a strictly defined shape and polarity in contrast to the potentially migratory mesenchymal cell. Many critical developmental processes involve the transition and interaction between epithelial and mesenchymal cells, processes which may be recapitulated in cancer. Growth factors and adhesion molecules are key regulators of embryonic development, playing a major role in signal transduction pathways governing fundamental aspects of cell function, shape and polarity.

Although signal transduction pathways controlling histogenesis are highly complex, they must be unravelled to understand the basic principles of morphogenesis. Activation of signal transduction pathways may also regulate stem/progenitor cell morphogenesis and tumour progression. Therefore our ultimate goal is to identify critical nodes in signal transduction pathways pivotal to development and cancer that may also provide new therapeutic targets.
Our laboratory combines biophysical approaches and advanced imaging techniques to study the mechanochemistry of cell-cell and cell-substrate adhesion (Click here to see more...). A dual pipette assay has been modified to measure the force required to separate cell doublets expressing different levels of type I or type II-cadherins (Fig. 1). Our studies indicate that initial adhesion not exceeding several nano-Newtons is reinforced only following cortical actin polymerization. Type II cadherin-7 and -11 is significantly less adhesive than E- and N-cadherin. These findings suggest that in vivo, cadherin-7 and -11 mediates transient adhesion, favouring motility and invasion, while E- and N-cadherin mediates stable adhesive contacts. Crosstalk mechanisms regulating the adhesive strength of cell-cell and cell-substrate adhesion are also being analysed using cell lines that undergo reversible epithelial–mesenchymal transition (EMT). We are currently developing transcriptomic and proteomic approaches to investigate the respective contribution of tyrosine kinase and phosphatase receptor signalling to EMT.
Other approaches are also being used in our laboratory to investigate EMT. Studies of in vivo cell adhesion and migration have benefited from the establishment of a transgenic mouse line driving the expression of transgenes in migratory neural crest cells following lineage specification (Fig. 2). The murine mammary gland is being used as a model to identify the molecular mechanisms governing induction, growth and branching morphogenesis (Fig. 3). Distinct signalling pathways including FGF10/FGFR2b, Wnt and Gli3 are active during the initial phase of mammary placode development. However, each placode is characterized by a unique molecular code established at initiation of induction. Our studies using a number of transgenic lines aim to further define this molecular code (Click here to see more...). The laboratory has characterized a murine breast stem progenitor cell that exhibits a basal phenotype. Targeting of an activated form of b-catenin in the basal layer of the developing mammary gland induces focal hyperplasia. These hyperplastic nodules develop in situ and invasive breast carcinomas of the basal phenotype. Using this tumour model we aim to identify tumour suppressors and oncogenes involved in oncogenesis of the basal carcinoma subtype. In parallel, the laboratory will pursue oncogenomic studies on human breast carcinoma with the basal phenotype.