LKB1 - p53 & CELL PLASTICITY - Grenoble · LKB1 - p53 & CELL PLASTICITY Group leader...

LKB1-p53&CELLPLASTICITY

Groupleader

ChantalTHIBERT(CR1,CNRS)

Labmembers

SakinaTORCH,MCF(UGA)AnthonyLUCAS,IE-2styearPhDstudent(INSERM,UGA)MarieMEVEL,M2student(ISPB,Lyon)

Labalumni

AncaRadu,PhDstudent(UGA,2014-2018)MaudSchweitzer,Techstudent(ESTBB,Lyon,2018)MatthieuAguilera,L3student(UGA,2018)ClaudieCOMEAU,M1student(SherbrookUniversity,Quebec,2017)MélissaBOUZAR,M1student(UGA,2017)

è We are exploring the metabolic regulations by LKB1 and p53 in development and cancer. Cellsadaptconstantlytheirmetabolismtotheirenvironmentthroughsignallingpathwaysthatactasbiosensors of nutrient availability. The kinase tumour suppressor LKB1 and its downstream kinasesubstrate AMPK are sensors of ATP levels. Under metabolic stress, they refurnish cell energy byactivatingATP-generatingand inhibitingATP-consumingprocessessuchasmTOR.Usinggeneticallyengineeredmousemodelsofspatio-temporalinactivationofLkb1,wehaverecentlyuncoveredthatLkb1/AMPKgovernscellfatebyconnectingmTORactivitytopyruvate-alaninecyclingandglutamate-glutamine conversion. We also highlighted that Lkb1 prevents oxidative DNA damages and p53activation,anecessaryprocessforcorrectcellfatebothinvitroandinvivo.WearecurrentlyexploringtheunderlyingmolecularmechanismsofLKB1-p53crosstalktobetterunderstandhowLKB1signallingunder metabolic stress impacts p53 non-transcriptional, transcriptional and

epigeneticsactivitiesinnormalandpathologicalconditions.OurgroupbelongstoPr.HainautlabattheInstituteforAdvancedBiosciencessince2016.We

arememberoftheFrenchnetworkCREST-NETonneuralcreststemcells.

Recent publications: -RaduA*,TorchS*,FauvelleF,Pernet-GallayK,BlervaqueR,LucasA,DelmasV,SchlattnerU,TricaudN,LafenechèreL,HainautP,TricaudN,PingaultV,BondurandN,BardeesyN,LarueL,ThibertC§andBillaudM.§LKB1specifiesneuralcrestcelllineagesthroughpyruvate-alaninecycling.InrevisionatScienceAdvances.*Co-first;§co-seniorandco-corresponding.- Cordier-Bussat M, Thibert C, Sujobert P, Fontaine E and Billaud M. Même l’effet Warburg est oxydable: coopération métabolique etdéveloppementtumoral.médecine/sciences,34:701-708.-CreuzetS*§,VialletJ*,GhawitianM,TorchS,ThéluJ,AlrajehM,RaduAG,BouvardD,CostagliolaF,LeBorgneM,Buchet-PoyauK,AznarN,BuschlenS,HosoyaH,ThibertC§andBillaudM§(2016)LKB1signalingincephalicneuralcrestcellsisessentialforvertebrateheaddevelopment.DevBiol.428:283-296*Co-first;§co-correspondingauthors.-MilleF+,ThibertC+,FombonneJ,RamaN,GuixC,HayashiH,CorsetV,ReedJandMehlenP.(2009)ThePatcheddependencereceptortriggersapoptosisthroughaDRAL-caspase9complex.NatCellBiol.11:739-46+Co-first.-ThibertC,TeilletMA,LapointeF,MazelinL,LeDouarinNMandMehlenP.(2003)InhibitionofneuroepithelialPatched-inducedapoptosisbySonichedgehog.Science,301:843-846.

Contact and information: Email: chantal.thibert@univ-grenoble-alpes.fr Phone : +33 (0)4 76 54 95 75 Researchgate: https://www.researchgate.net/profile/Chantal_Thibert

LKB1

Cellmetabolism&cellfate:

Cellmodels:

Neuralcreststemcells

Lungtumorcells

p53

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