Plasticité Gliale

Co-Leaders

Research center

9 Quai Saint-Bernard Université Pierre et Marie Curie, Campus Jussieu, Bâtiments A-B-C
75005 Paris
Michel Labouesse

Institution

Inserm
CNRS
Université Pierre et Marie Curie

Laboratory

Neuroscience Paris Seine
U1130 UMR8246 UMCR18

Mots clefs

Neural stem cells
Glial cells
Brain tumors
cellular biology
Therapeutics
Available to host a PhD student

publications

Assad Kahn S, Costa SL, Gholamin S, Nitta RT, Dubois LG, Fève M, Zeniou M, Coelho PL, El-Habr E, Cadusseau J, Varlet P, Mitra SS, Devaux B, Kilhoffer MC, Cheshier SH, Moura-Neto V, Haiech J, Junier MP, Chneiweiss H.The anti-hypertensive drug prazosin inhibits glioblastoma growth via the PKCδ-dependent inhibition of the AKT pathway.EMBO Mol Med. 2016 May 2;8(5):511-26. doi: 10.15252/emmm.201505421.

Turchi L, Debruyne DN, Almairac F, Virolle V, Fareh M, Neirijnck Y, Burel-Vandenbos F, Paquis P, Junier MP, Van Obberghen-Schilling E, Chneiweiss H,Virolle T. Tumorigenic Potential of miR-18A* in Glioma Initiating Cells Requires NOTCH-1 Signaling. Stem Cells. 2013 31:1252-65.

Thirant C, Galan-Moya EM, Dubois LG, Pinte S, Chafey P, Broussard C, Varlet P, Devaux B,Soncin F, Gavard J, Junier MP,Chneiweiss H. Differential proteomic analysis of human glioblastoma and neural stem cells reveals HDGF as a novel angiogenic secreted factor.Stem Cells. 2012 May;30(5):845-53.

Fareh M, Turchi L, Virolle V, Debruyne D, Almairac F, de-la-Forest Divonne S, Paquis P, Preynat-Seauve O, Krause KH, Chneiweiss H, Virolle T The. miR 302-367 cluster drastically affects self-renewal and infiltration properties of glioma-initiating cells through CXCR4 repression and consequent disruption of the SHH-GLI-NANOG network.Cell Death Differ. 2012 Feb;19(2):232-44.

Galan-Moya EM, Le Guelte A, Lima-Fernandes E, Thirant C, Dwyer J, Bidere N, Couraud PO, Scott M, Junier MP Chneiweiss H, Gavard J.?Brain endothelial cells maintain glioblastoma stem-like cell expansion through the mTOR pathway. EMBO Report 2011,12: 470-6.

Silvestre DC, Pineda Marti JR, Hoffschir F, Studler JM,Mouthon MA, Pflumio F, Junier MP, Chneiweiss H,Boussin FD. Alternative Lengthening of Telomeres in Human Glioma Stem Cells. Stem Cells. 2011 Mar;29(3):440-

Fields of research

Neurophysiology / systems neuroscience

Research Theme

The main focus of our research is the plasticity and development of human brain tumors
We are interested in understanding how interactions between cell intrinsic and extrinsic signaling pathways control the stem and tumor-initiating properties of glioma stem cells.

Our project aims at characterizing intra- and extracellular molecular pathways that restrict the stem-like potential, and consequently the tumorigenicity of human glioma stem cells (GSC), as compared to human neural stem cells (NSC). It takes advantage of the unique model offered by the couple formed by GSC and their non-tumorigenic counterparts miR-302-367-GSC. Recent advances show that the metabolic changes could be at the core of tumorigenesis. They have noteworthy led to the identification of mutations in metabolic enzymes that drive cancer pathogenesis, of metabolic markers of cancer progression, and to the recognition that metabolic changes may affect the cell phenotype. In light of these discoveries, we postulate that a change in cell phenotype as radical as that induced by miR-302-367 should result in metabolic alterations instrumental in the loss of tumorigenic and stem-like properties

We will specifically:
1. Determine the mechanism and functional consequences of the metabolite rearrangements accompanying the irreversible
repression of GSC stem and tumor-initiating properties.
2. Extend the identification of compounds targeting GSC and and transfer

Lab rotation

Metabolic and epigenetic reprogramming in glioma cells

Chercheur responsable: 

CHNEIWEISS Hervé

Dates: 

1 September 2016 - 31 December 2016

Date limite de candidature: 

1 September 2016

Lab rotation proposal: 3 months 

~ Sep-Dec 2016 ~ Jan-March 2017 ~ Apr-June 2017

Project:

Strongly altered cellular metabolism is a common feature of cancer cells, and participates in their development and maintenance. We performed metabolome profiling of cancer stem cells isolated from glioblastoma (GSC) prior and after expression of the micro-RNA cluster miR-302-367 that inhibits GSC stem and tumour-initiating properties (Fareh et al, Cell Death & Diff 2012). We identified unexpected rearrangements of several metabolic modules linking epigenetic regulations and cancer features, and pinpointed specific metabolic pathways that undergo reprogramming following the exit of GSC from their stem state. We further showed that mimicking these metabolic reprogramming through genetic and pharmacological manipulations oppose cancer features in glioblastoma stem cells isolated from patient brains presenting distinct genomic anomalies (manuscript in preparation)The objectives of our project will aim at:- Deciphering the fine molecular mechanisms by which these rearrangements in metabolic modules affect the epigenetic regulations observed. This will be achieved using cell biology, biochemistry and molecular biology technics combined with bioinformatics analysis of data sets integrating the metabolic, genetic and epigenetic changes in the cells submitted to modulation of the metabolic module under scrutiny.-        Evaluating the clinical relevance of the findings. This will be achieved by in vitro sphere assays and animal models of glioblastoma combined with BRET or FRET luminescent sensors to monitor the metabolic state of the cells in live animals.

AddressNeuroscience Paris Seine - Université Pierre et Marie Curie 7-9 quai Saint Bernard 75005 Paris

Phone number+33 1 44 27 33 65 ; Mail: marie-pierre.junier@inserm.fr

Website

Superviseur: 

Elias EL-HABR or Ghislaine MORVAN