Responsables de l’équipe
-
Yegor VASSETZKY
Responsable de l’équipe "Dynamique de la chromatine et métabolisme dans le cancer"
DR1 CNRS
-
Svetlana DOKUDOVSKAYA
Responsable de l’équipe "Dynamique de la chromatine et métabolisme dans le cancer"
DR2 CNRS
Thèmes de recherche
Nous nous intéressons aux premiers stades de l’oncogenèse dans le but de trouver des biomarqueurs précoces du cancer et d’identifier de nouvelles approches de prévention et de traitement. Nous développons les thèmes de recherche suivants:
- Nous développons un système permettant d’identifier une cellule cancéreuse dès l’événement oncogénique dans le but de trouver des biomarqueurs précoces du cancer.
- Nous étudions comment les virus et leurs protéines déclenchent le cancer et comment ils affectent la stabilité du génome, modulent l’organisation nucléaire.
- Nous analysons les changements dans la transcription des gènes et l’organisation du génome liés aux translocations chromosomiques avec le but de trouver des thérapies innovantes.
Notre équipe s’intéresse également à différents aspects de la régulation de l’homéostasie cellulaire par la voie mTORC1. En tant qu’élément central, mTORC1 intègre des signaux provenant d’une grande variété de stimui intracellulaires et extracellulaires, notamment des acides aminés, des facteurs de croissance, de l’énergie, de l’oxygène, etc. En fonction de la nature du signal, mTORC1 va conduire la cellule soit vers la voie anabolique favorisant la prolifération et la survie, soit vers la voie catabolique en contrôlant l’autophagie. Nous étudions la réponse de mTORC1 aux nutriments et aux agents endommageant l’ADN, en nous concentrant sur le régulateur amont essentiel de mTORC1, le complexe SEA/GATOR. Nous cherchons à comprendre comment l’altération de la signalisation de mTORC1 due à l’expression aberrante des membres de SEA/GATOR influence le fonctionnement des lysosomes et des mitochondries et la réponse aux dommages de l’ADN. Les composants SEA/GATOR étant des suppresseurs de tumeurs et impliqués dans la résistance aux médicaments anticancéreux, la compréhension de leur fonctionnement favorisera le développement de thérapies efficaces contre le cancer.
Nos membres
-
Joëlle WIELS
DREM CNRS
-
Xinran SONG
Doctorante
-
Hanxiao ZHANG
Doctorante
-
Zhenrui PAN
Doctorante
-
Victoria GINESTET
Doctorante
-
Anna KARPUKHINA
Doctorante
-
Junyi FENG
Doctorante
Alumni
- Anna SHMAKOVA, Doctorante
- Yana KOZHEVNIKOVA, Etudiante en M2 2022-2023
- Ivan TSIMAILO, Etudiant en M2 2022-2023
- Yahir Alberto LOISSELL-BALTAZAR, Doctorant
Nos publications
Shmakova A, Tsimailo I, Kozhevnikova Y, Gérard L, Boutboul D, Oksenhendler E, Tuaillon E, Rivault A, Germini D, Vassetzky Y*, Beaumelle B. HIV-1 Tat is present in the serum of people living with HIV-1 despite viral suppression. Int J Infect Dis. 2024 Mar 4:106994. doi: 10.1016/j.ijid.2024.106994. Epub ahead of print. PMID: 38447753. *Corresponding author
Anna Shmakova, Coline Hugot, Yana Kozhevnikova, Anna Schwager Karpukhina, Ivan Tsimailo, Laurence Gérard, David Boutboul, Eric Oksenhendler, Olga Szewczyk-Roszczenko, Piotr Roszczenko, Kamila Buzun, Eugene V Sheval, Diego Germini, Yegor Vassetzky Chronic HIV-1 Tat action induces HLA-DR downregulation in B cells: A mechanism for lymphoma immune escape in people living with HIV J Med Virol. 2024 Feb;96(2):e29423. doi: 10.1002/jmv.29423. PMID: 38285479 DOI: 10.1002/jmv.29423
Reynand Jay Canoy, Anna Shmakova, Anna Karpukhina , Nikolai Lomov, Eugenia Tiukacheva, Yana Kozhevnikova, Franck André, Diego Germini, Yegor Vassetzky Specificity of cancer-related chromosomal translocations is linked to proximity after the DNA double-strand break and subsequent selection. NAR Cancer 2023 Sep 23;5(3):zcad049. doi: 10.1093/narcan/zcad049.
Olga Klaudia Szewczyk-Roszczenko, Piotr Roszczenko, Anna Shmakova, Nataliya Finiuk, Serhii Holota, Roman Lesyk , Anna Bielawska, Yegor Vassetzky, Krzysztof Bielawski The Chemical Inhibitors of Endocytosis: From Mechanisms to Potential Clinical Applications. Сells. 2023 Sep 19;12(18):2312. doi: 10.3390/cells12182312.
Pan Z, Zhang H, Dokudovskaya S. The Role of mTORC1 Pathway and Autophagy in Resistance to Platinum-Based Chemotherapeutics. Int J Mol Sci. 2023 Jun 26;24(13):10651. doi: 10.3390/ijms241310651.
Shmakova A, Vassetzky Y. lncRNA: A new danger for genome integrity. Int J Cancer. 2023 Apr 1;152(7):1288-1289. doi: 10.1002/ijc.34397.
Sall FB, Shmakova A, Karpukhina A, Tsfasman T, Lomov N, Canoy RJ, Boutboul D, Oksenhendler E, Toure AO, Lipinski M, Wiels J, Germini D, Vassetzky Y. Epstein-Barr virus reactivation induces MYC-IGH spatial proximity and t(8;14) in B cells. J Med Virol. 2023 Mar;95(3):e28633. doi: 10.1002/jmv.28633.
Chernyavskij DA, Pletjushkina OY, Kashtanova AV, Galkin II, Karpukhina A, Chernyak BV, Vassetzky YS, Popova EN. Mitochondrial Oxidative Stress and Mitophagy Activation Contribute to TNF-Dependent Impairment of Myogenesis. Antioxidants (Basel). 2023 Mar 1;12(3):602. doi: 10.3390/antiox12030602.
Tiukacheva EA, Ulianov SV, Karpukhina A, Razin SV, Vassetzky Y. 3D genome alterations and editing in pathology. Mol Ther. 2023 Apr 5;31(4):924-933. doi: 10.1016/j.ymthe.2023.02.005.
Canoy RJ, André F, Shmakova A, Wiels J, Lipinski M, Vassetzky Y, Germini D. Easy and robust electrotransfection protocol for efficient ectopic gene expression and genome editing in human B cells. Gene Ther. 2023 Feb;30(1-2):167-171. doi: 10.1038/s41434-020-00194-x.
Shmakova AA, Popov VS, Romanov IP, Khabibullin NR, Sabitova NR, Karpukhina AA, Kozhevnikova YA, Kurilina EV, Tsokolaeva ZI, Klimovich PS, Rubina KA, Vassetzky YS, Semina EV. Urokinase System in Pathogenesis of Pulmonary Fibrosis: A Hidden Threat of COVID-19. Int J Mol Sci. 2023 Jan 10;24(2):1382. doi: 10.3390/ijms24021382.
Shmakova A, Lomov N, Viushkov V, Tsfasman T, Kozhevnikova Y, Sokolova D, Pokrovsky V, Syrkina M, Germini D, Rubtsov M, Vassetzky Y. Cell models with inducible oncogenic translocations allow to evaluate the potential of drugs to favor secondary translocations. Cancer Commun (Lond). 2023 Jan;43(1):154-158. doi: 10.1002/cac2.12370.
Viushkov VS, Lomov NA, Rubtsov MA, Vassetzky YS. Visualizing the Genome: Experimental Approaches for Live-Cell Chromatin Imaging. Cells. 2022 Dec 16;11(24):4086. doi: 10.3390/cells11244086.
Séguy L, Daressy F, Lahlil S, Corvaisier S, Dumontet V, Litaudon M, Apel C, Roussi F, Wiels J, Robert A, Groo AC, Malzert-Fréon A. In vitro evaluation of NA1-115-7-loaded nanoemulsions, an MCL-1-specific inhibitor of natural origin, intended to treat B-cell lymphoproliferative disorders after oral administration. Int J Pharm. 2023 Jan 5;630:122433. doi: 10.1016/j.ijpharm.2022.122433.
Canoy RJ, Shmakova A, Karpukhina A, Shepelev M, Germini D, Vassetzky Y. Factors That Affect the Formation of Chromosomal Translocations in Cells. Cancers (Basel). 2022 Oct 18;14(20):5110. doi: 10.3390/cancers14205110.
Valyaeva AA, Tikhomirova MA, Potashnikova DM, Bogomazova AN, Snigiryova GP, Penin AA, Logacheva MD, Arifulin EA, Shmakova AA, Germini D, Kachalova AI, Saidova AA, Zharikova AA, Musinova YR, Mironov AA, Vassetzky YS, Sheval EV. Ectopic expression of HIV-1 Tat modifies gene expression in cultured B cells: implications for the development of B-cell lymphomas in HIV-1-infected patients. PeerJ. 2022 Oct 18;10:e13986. doi: 10.7717/peerj.13986.
Daressy F, Séguy L, Favre L, Corvaisier S, Apel C, Groo AC, Litaudon M, Dumontet V, Malzert-Fréon A, Desrat S, Roussi F, Robert A, Wiels J. NA1-115-7, from Zygogynum pancheri, is a new selective MCL-1 inhibitor inducing the apoptosis of hematological cancer cells but non-toxic to normal blood cells or cardiomyocytes.
Biomed Pharmacother. 2022 Oct;154:113546. doi: 10.1016/j.biopha.2022.113546. Epub 2022 Aug 18.Kiseleva E, Serbina O, Karpukhina A, Mouly V, Vassetzky YS. Interaction between mesenchymal stem cells and myoblasts in the context of facioscapulohumeral muscular dystrophy contributes to the disease phenotype. J Cell Physiol. 2022 Aug;237(8):3328-3337. doi: 10.1002/jcp.30789.
Ichim G, Gibert B, Adriouch S, Brenner C, Davoust N, Desagher S, Devos D, Dokudovskaya S, Dubrez L, Estaquier J, Gillet G, Guénal I, Juin PP, Kroemer G, Legembre P, Levayer R, Manon S, Mehlen P, Meurette O, Micheau O, Mignotte B, Nguyen-Khac F, Popgeorgiev N, Poyet JL, Priault M, Ricci JE, Riquet FB, Susin SA, Suzanne M, Vacher P, Walter L, Mollereau B. Keeping Cell Death Alive: An Introduction into the French Cell Death Research Network. Biomolecules. 2022 Jun 28;12(7):901. doi: 10.3390/biom12070901.
Zakharova VV, Magnitov MD, Del Maestro L, Ulianov SV, Glentis A, Uyanik B, Williart A, Karpukhina A, Demidov O, Joliot V, Vassetzky YS, Mège RM, Piel M, Razin SV, Ait-Si-Ali S. SETDB1 fuels the lung cancer phenotype by modulating epigenome, 3D genome organization and chromatin mechanical properties. Nucleic Acids Res. 2022 May 6;50(8):4389-4413. doi: 10.1093/nar/gkac234.
Lai HT, Canoy RJ, Campanella M, Vassetzky Y, Brenner C. Ca2+ Transportome and the Interorganelle Communication in Hepatocellular Carcinoma. Cells. 2022 Feb 26;11(5):815. doi: 10.3390/cells11050815.
Liu D, Peyre F, Loissell-Baltazar YA, Courilleau D, Lacas-Gervais S, Nicolas V, Jacquet E, Dokudovskaya S, Taran F, Cintrat JC, Brenner C. Identification of Small Molecules Inhibiting Cardiomyocyte Necrosis and Apoptosis by Autophagy Induction and Metabolism Reprogramming. Cells. 2022 Jan 29;11(3):474. doi: 10.3390/cells11030474.
Kurnaeva MA, Zalevsky AO, Arifulin EA, Lisitsyna OM, Tvorogova AV, Shubina MY, Bourenkov GP, Tikhomirova MA, Potashnikova DM, Kachalova AI, Musinova YR, Golovin AV, Vassetzky YS, Sheval EV. Molecular Coevolution of Nuclear and Nucleolar Localization Signals inside the Basic Domain of HIV-1 Tat. J Virol. 2022 Jan 12;96(1):e0150521. doi: 10.1128/JVI.01505-21.
Loissell-Baltazar YA, Dokudovskaya S. SEA and GATOR 10 Years Later. Cells. 2021 Oct 8;10(10):2689. doi: 10.3390/cells10102689.
Robert A, Wiels J. Shiga Toxins as Antitumor Tools. Toxins (Basel). 2021 Sep 28;13(10):690. doi: 10.3390/toxins13100690
Karpukhina A, Galkin I, Ma Y, Dib C, Zinovkin R, Pletjushkina O, Chernyak B, Popova E, Vassetzky Y. Analysis of genes regulated by DUX4 via oxidative stress reveals potential therapeutic targets for treatment of facioscapulohumeral dystrophy. Redox Biol. 2021 Jul;43:102008. doi: 10.1016/j.redox.2021.102008.
Karpukhina A, Tiukacheva E, Dib C, Vassetzky YS. Control of DUX4 Expression in Facioscapulohumeral Muscular Dystrophy and Cancer. Trends Mol Med. 2021 Jun;27(6):588-601. doi: 10.1016/j.molmed.2021.03.008.
Daressy F, Malard F, Seguy L, Guérineau V, Apel C, Dumontet V, Robert A, Groo AC, Litaudon M, Bignon J, Desrat S, Malzert-Fréon A, Wiels J, Lescop E, Roussi F. Drimane Derivatives as the First Examples of Covalent BH3 Mimetics that Target MCL-1. ChemMedChem. 2021 Jun 7;16(11):1788-1797. doi: 10.1002/cmdc.202100011. Epub 2021 Mar 23.
Akbay B, Germini D, Bissenbaev AK, Musinova YR, Sheval EV, Vassetzky Y, Dokudovskaya S. HIV-1 Tat Activates Akt/mTORC1 Pathway and AICDA Expression by Downregulating Its Transcriptional Inhibitors in B Cells. Int J Mol Sci. 2021 Feb 4;22(4):1588. doi: 10.3390/ijms22041588.
Ulianov SV, Zakharova VV, Galitsyna AA, Kos PI, Polovnikov KE, Flyamer IM, Mikhaleva EA, Khrameeva EE, Germini D, Logacheva MD, Gavrilov AA, Gorsky AS, Nechaev SK, Gelfand MS, Vassetzky YS, Chertovich AV, Shevelyov YY, Razin SV. Order and stochasticity in the folding of individual Drosophila genomes. Nat Commun. 2021 Jan 4;12(1):41. doi: 10.1038/s41467-020-20292-z.
Valyaeva AA, Zharikova AA, Kasianov AS, Vassetzky YS, Sheval EV. Expression of SARS-CoV-2 entry factors in lung epithelial stem cells and its potential implications for COVID-19. Sci Rep. 2020 Oct 20;10(1):17772. doi: 10.1038/s41598-020-74598-5.
Robert A, Pujals A, Favre L, Debernardi J, Wiels J. The BCL-2 family protein inhibitor ABT-737 as an additional tool for the treatment of EBV-associated post-transplant lymphoproliferative disorders. Mol Oncol. 2020 Oct;14(10):2520-2532. doi: 10.1002/1878-0261.12759. Epub 2020 Aug 12.
Sorokin DV, Arifulin EA, Vassetzky YS, Sheval EV. Live-Cell Imaging and Analysis of Nuclear Body Mobility. Methods Mol Biol. 2020;2175:1-9. doi: 10.1007/978-1-0716-0763-3_1.
Germini D, Sall FB, Shmakova A, Wiels J, Dokudovskaya S, Drouet E, Vassetzky Y. Oncogenic Properties of the EBV ZEBRA Protein. Cancers (Basel). 2020 Jun 5;12(6):1479. doi: 10.3390/cancers12061479.
Shmakova A, Germini D, Vassetzky Y. HIV-1, HAART and cancer: A complex relationship. Int J Cancer. 2020 May 15;146(10):2666-2679. doi: 10.1002/ijc.32730.
Debernardi J, Pioche-Durieu C, Cam EL, Wiels J, Robert A. Verotoxin-1-Induced ER Stress Triggers Apoptotic or Survival Pathways in Burkitt Lymphoma Cells.
Toxins (Basel). 2020 May 11;12(5):316. doi: 10.3390/toxins12050316.Akbay B, Shmakova A, Vassetzky Y, Dokudovskaya S. Modulation of mTORC1 Signaling Pathway by HIV-1. Cells. 2020 Apr 28;9(5):1090. doi: 10.3390/cells9051090.