Vincent GUEN

Cilia are hair-like projections that assemble at the surface of cells in various tissues of multicellular organisms through a complex cell biological process called ciliogenesis. Cilia can assemble as single structures per cell (i.e. non-motile primary cilia), which act as cell signaling centers that dictate cell fate, or can be assembled in distinct cell types as many copies per cell (i.e. motile cilia) that beat to move fluids at the cell surface. Thus, cilia regulate the development of multicellular organisms. Abnormal ciliogenesis and/or ciliary signaling results in severe developmental disorders collectively named ciliopathies as well as cancers. Our work has focused over the last decade on the biology of primary cilia. We have identified two new ciliopathies (STAR and AL KAISSI syndromes). We discovered a role for primary cilia in normal breast development and in a subtype of breast cancers (i.e. claudin-low), which reflects a critical role for primary cilia in controlling normal and cancer stem cells downstream of epithelial plasticity programs. We have developed over the recent years innovative microscopy imaging techniques and used scRNAseq to study cilia in whole-mount tissues and stem cell-derived organoids. We have also recently developed new techniques to discover small-molecule inhibitors of ciliogenesis to facilitate our research on the biology of primary cilia in development and cancer.

Selected recent publications:

Dupuy MM, Juin PP, Guen VJ. Using mammary organoids to study cilia. Methods In Cell Biology. 2022. In press.

Wilson MM, Callens C, Le Gallo M, Mironov S, Ding Q, Salamagnon A, Chavarria TE, Viel R, Peasah AD, Bhutkar A, Martin S, Godey F, Tas P, Kang HS, Juin PP, Jetten AM, Visvader JE, Weinberg RA, Attanasio M, Prigent C, Lees JA, Guen VJ. An EMT-primary cilium-GLIS2 signaling axis regulates mammogenesis and claudin-low breast tumorigenesis. Science Advances. 2021 Oct 29;7(44):eabf6063. doi:10.1126/sciadv.abf6063.

Duclos M, Prigent C, Le Borgne R, Guen VJ. Three-dimensional imaging of organoids to study primary ciliogenesis during ex vivo organogenesis. J Vis Exp. 2021 May 14;(171). doi: 10.3791/62365.

Guen VJ, Prigent C. Targeting Primary Ciliogenesis with Small-Molecule Inhibitors. Cell Chem Biol. 2020 Oct 15;27(10):1224-1228. doi:10.1016/j.chembiol.2020.07.018.

Wilson MM, Weinberg RA, Lees JA, Guen VJ. Emerging Mechanisms by which EMT Programs Control Stemness. Trends Cancer. 2020 Sep;6(9):775-780. doi:10.1016/j.trecan.2020.03.011.

Guen VJ, Edvardson S, Fraenkel ND, Fattal-Valevski A, Jalas C, Anteby I, Shaag A, Dor T, Gillis D, Kerem E, Lees JA, Colas P, Elpeleg O. A homozygous deleterious CDK10 mutation in a patient with agenesis of corpus callosum, retinopathy, and deafness. Am J Med Genet A. 2018 Jan;176(1):92-98. doi:10.1002/ajmg.a.38506.

Guen VJ, Chavarria TE, Kröger C, Ye X, Weinberg RA, Lees JA. EMT programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling. Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):E10532-E10539. doi: 10.1073/pnas.1711534114.