Vincent GUEN

Research - The CP²C group is interested in understanding mechanisms of cell plasticity contributing to normal development and disease progression. Our work focuses on phenotypic plasticity driven by epithelial-mesenchymal transition and ciliary signaling in cellular ecosystems. We use cutting-edge imaging and genomics technologies together with innovative animal models, organoids and chemical tools to map and understand cell state transitions in normal and disease states ranging from ciliopathies to cancers.

Additional background - Tissue development and disease progression relies on distinct cell types that communicate and transit in distinct cell states in cellular ecosystems. Epithelial-Mesenchymal Transition is a developmental program that can be activated to induce cell state transition in epithelia and carcinomas. It regulates the formation of primary cilia and thereby cell motility and stemness. Primary cilia act as cell signaling hubs in cells where signaling components are processed to regulate autocrine and paracrine signaling in cellular ecosystems in normal and disease states.

Past accomplishments -
Our work revealed two new ciliopathies (i.e. developmental disorders caused by abnormal cilia, STAR and AL KAISSI syndromes). We discovered a role for primary cilia downstream of EMT programs in normal breast development and in the formation of a subtype of breast cancers (i.e. claudin-low).

Selected publications:

Tessier CE*, Derrien J*,Dupuy AMM, Pelé T, Moquet M, Roul J, Douillard E, El Harrif C, Pinson X, Le Gallo M, Godey F, Tas P, Viel R, Prigent C, Letouzé E, Suzanne P, Dallemagne P, Campone M, Weinberg RA, Lees JA, Juin PP, Guen VJ. Primary cilia promote EMT-induced triple-negative breast tumor heterogeneity and resistance to therapy. Under revision. 

Tessier CE, Dupuy AMM, Pelé T, Juin PP, Lees JA, Guen VJ. EMT and primary ciliogenesis: For better or worse in sickness and in health. Genesis. 2024 Feb;62(1):e23568. doi: 10.1002/dvg.23568. Epub 2023 Nov 9. PMID: 37946671.

Dupuy AMM, Juin PP, Guen VJ. Using mammary organoids to study cilia. Methods Cell Biol. 2023;175:221-233. doi: 10.1016/bs.mcb.2022.09.010. Epub 2022 Nov 18. PMID: 36967142.

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.