Team Hugues DUFFAU – Jean-Philippe HUGNOT

Brain plasticity, stem cells and diffuse low-grade gliomas

Project Control of differentiation and proliferation of neural stem cells and tumor cells (gliomas)

PRINCIPAL INVESTIGATOR

Jean-Philippe Hugnot
PU, UM

IGF staff involved
Hugues DUFFAU
PU-PH, UM
Luc BAUCHET
PH, CHU
Catherine GOZE
MCU-PH, UM
Chantal RIPOLL
IR, INSERM
Donovan PINEAU
Post-doc, INSERM
Léonor GARCIA
PhD, UM
Kasandra AGUILAR
PhD, UM
Joey Abou CHAAYA
PhD, UM

We study the genetic mechanisms and signaling pathways regulating neural stem cells, exploring self-renewal, proliferation, differentiation, migration and quiescence. Our focus is specifically on canonical pathways (Hippo/YAP,..) and GPCR receptors, with an emphasis on adult spinal cord ependymal stem cells and low-grade glioma stem cells with the IDH1 mutation. Our research aims to understand the formation of molecular heterogeneity in these tumours and to decipher tumour progression. We are also looking for markers of progression, identifying new therapeutic targets and studying the mode of action of recent molecules against IDH1 tumours.

Genes and signalling controlling differentiation and self-renewal of cancer stem cells

Stem cell niche in the adult spinal cord

Genes and signalling controlling differentiation and self-renewal of cancer stem cells

1/ Creation and molecular annotation (WES, scRNA seq, etc.) of a biobank of IDH1-mutated glioma lines derived from resections by Prof H Duffau
2/ Influence of the tumour environment on cancer stem cells
3/ Genetic control of proliferation and differentiation
4/ Search for biomarkers of tumour progression and new therapeutic targets
5/ Mode of action of IDH1 inhibitors

Models set up in the team to study low-grade gliomas

Main publications
• Augustus M., et al (2021) Cancers (Basel). 13(9):2107.
• Guelfi S, et al (2021) Cancers (Basel). 13(21):5393.
• Azar S, et al (2018) Glia 66(2):239-255.

Funding
• 2024 Servier, La Ligue
• 2023 PRTK, GSO Emergence, ARTC SUD, ARTC, Des étoiles dans la mer, Emball’iso
• 2022 INCA
• 2021 ANR

Collaborations
• L Zhang, S Lv, Jinfeng labs, China
• C Plaisier, Temple, USA
• D Boquet, C Truillet, A Mabondzo CEA, Saclay
• F Denat, Univ. Dijon
• L Stuani, IRCM, Montpellier

Alumni
● Meera Augustus (PhD, 2018-2021)
● S Guelfi (PhD, 2013-2016)
● S Azar (PhD, 2013-2017)

Patents
• Hugnot, JP, Guichet, PO,;Teigell, M; Bieche, Y, ; Lidereau R; Joubert, D; Bauchet, L, Rigau, V ; European Patent 10305805.3, PCT/EP2011/062578,
• Hugnot, JP; Guichet, PO; Serguera C; Mallet J European Patent 10305804.6, WO_2012_010675_A2

Stem cell niche in the adult spinal cord

We are analysing the diversity of stem cells present in a niche around the central canal of the spinal cord, in both mice and humans, using spinal cord samples from organ donors aged between 17 and 83 years (Dr L Bauchet). Our aim is to investigate the genes and signaling pathways that regulate the persistence of these cells in the spinal cord. These cells have a latent program to differentiate into oligodendrocytes, and our study focuses on how to direct this differentiation.

Comparison of the central canal region of the spinal cord in different species (from Becker T, Becker C, Hugnot JP, Progress in Neurobiology, 2018)

Main publications
• Ripoll C, et al (2023) Cell Mol Life Sci.80(8):208.
• Chevreau T, Ghazale H, Ripoll C, et al (2021) Cells. 10(12):3332.
• Ghazale H, Ripoll C et al (2019) Stem Cell Reports. 12(5):1159-1177.

Funding
• 2023 Wings for life
• 2022, 2023 ARSEP
• 2021 IRME, AFM

Collaborations
• E Sundström, Karolinska Institute
• N Guerout, SPPIN, Paris

Alumni
• Tino Chevreau
• Hussein Ghazale