Home Research Multi-factorial diseases J. Imbert

Jean Imbert

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DR Inserm
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Phone: +33(0)491 828 703
FAX:    +33(0)491 828 701
Cell:     +33(0)622 313 425

Research interests

My research focuses on the characterization of the transcriptional mechanisms and networks involved in the T lymphocyte activation and various pathologies including cancer. To carry out the collaborative projects covering this theme, we are using a large set of experimental and computational-based approaches in order to:

1) Identify the putative regulatory regions associated with coregulated genes (phylogenomics, Mnase-seq, FAIRE-seq).

2) Map the epigenomic modifications of chromatin and DNA (histone marks and PolII ChIp-seq, Methyl-seq).

3) Identify the genomic targets of associated sequence-specific TFs (ChIP-seq).

4) Identify the regulatory motifs of coregulated genes (motif search, comparative genomics, phylogenomics, meta-analysis, etc.)

5) Identify the specific TFs associated with the characterized regulatory elements (EMSA, reporter gene assays, etc.)

6) Confirm the functional link between a given TF and its target genes (ChIP, functional assays, bioinformatics, text mining, etc.)

7) Integrate large epigenomics datasets with transcriptome analysis to describe the regulatory networks sustaining the analysed biological process.

Projects

1) Transcriptional control of the expression of the IL2RA gene: Identification and analysis of the regulatory regions involved in T cell differentiation was continued in collaboration with Pierre Ferrier at CIML and Warren Leonard at NIH (Kim et al., 2006). In collaboration with José Rocca-Serra (IRU Marseille) and Alain Arnéodo (ENS Lyon) we have resolved the dynamic 3D structure of the human IL2RA promoter using Atomic Force Microscopy (AFM) (Milani et al., 2011).

 

2) Bioinformatics and transcriptional regulations: Development of new computational tools for the integrated analysis of transcriptomics data in collaboration with Denis Puthier at TAGC (TBrowser: Lopez et al., 2009; Interactome Browser: Lepoivre et al., 2012) (TAGC), and for ChIP-on-chip and ChIP-seq data analysis in collaboration with Pierre Ferrier at CIML (CoCAS: Benoukraf et al., 2010).

 

3) Epigenetics and Epigenomics: The creation of the glass DNA microarray service (April 2008) and of the high throughput sequencing facility (April 2009) have largely expended the available experimental tools (ChIP-on-chip, ChIP-seq, Methyl-seq, Mnase-seq, FAIRE-seq, etc.). These technological developments have induced a considerable acceleration of the epigenetics/epigenomics projects mostly in collaboration (Pekowska et al., 2011). We are currently deciphering the transcriptional EGR1 and CTNNB1 (b-catenin) network involved in glioblastoma in collaboration with Thierry Virolle, Inserm Nice.

 

4) Transcriptional networks in breast cancer: We have discovered a negative feedback loop associating ERBB2 and GATA4 in collaboration with Daniel Birnbaum at CRCM (Hua et al., 2009; Birnbaum et al., 2009). This result has provided the first molecular mechanism explaining the role of GATA4 in cancer cells, a newly classified anti-oncogene. We are currently analyzing the respective roles of ERBB2a and ERBB2b, the 2 major isoforms of this well-known oncogene.

 

Other responsabilities

 

1) Scientific director of the IBiSA Transcriptomics and Genomics Marseille-Luminy (TGML) platform

 

2) Founding member and partner of the National Infrastructure France Genomics

 

3) Director of the Regional Coordination of Life Science Platform CoReBio PACA

 

4) Chairman of the Scientific Committee for Inserm Workshops.

Selected publications

1. Lepoivre, C., Bergon, A., Lopez, F., Perumal, N.B., Nguyen, C., Imbert, J., and Puthier, D. TranscriptomeBrowser 3.0: introducing a new compendium of molecular interactions and a new visualization tool for the study of gene regulatory networks. BMC. Bioinformatics. 13, 19, 2012.

2. Pekowska, A., Benoukraf, T., Zacarias-Cabeza, J., Belhocine, M., Koch, F., Holota, H., Imbert, J., Andrau, J.C., Ferrier, P., and Spicuglia, S. (2011). H3K4 tri-methylation provides an epigenetic signature of active enhancers. EMBO J. 30, 4198-4210, 2011.

3. Milani, P., Marilley, M., Sanchez-Sevilla, A., Imbert, J., Vaillant, C., Argoul, F., Egly, J.M., Rocca-Serra, J. and Arneodo, A. Mechanics of the IL2RA gene activation revealed by modeling and atomic force microscopy. PLOS One, 6:e18811, 2011.

4. Birnbaum, D., Sircoulomb, F. and Imbert,J. A reason why the ERBB2 gene is amplified and not mutated in breast cancer. Cancer Cell Int., 9:5, 2009.

5. Hua, G., Zhu, B., Rosa, F., Deblon, N., Adelaide, J., Kahn-Perles, B., Birnbaum, D. and Imbert, J. A negative feedback regulatory loop associates the tyrosine kinase receptor ERBB2 and the transcription factor GATA4 in breast cancer cells. Mol. Cancer Res., 7:402-414, 2009.

6. Benoukraf, T., Cauchy, P., Fenouil, R., Jeanniard, A., Jaeger, S., Thieffry, D., Imbert, J., Andrau, J.C., Spicuglia, S. and Ferrier, P. CoCAS: A ChIP-on-Chip Analysis Suite. Bioinformatics, 25:954-955, 2009.

7. Lopez, F., Textoris, J., Bergon, A., Granjeaud, S., Didier, G., Remy, E., Imbert, J., Nguyen, C. and Puthier, D. TBrowser: a new tool to productively mine thousands of transcriptional signatures derived from public microarray experiments. PLoS ONE, 3 (12):e4001, 2008.

8. Vicart, A., Lefebvre, T., Imbert, J., Fernandez, A. and Kahn-Perles, B. Increased chromatin recruitment of Sp1 in dividing cells by PP2A-mediated dephosphorylations J.Mol.Biol., 364:897-908, 2006.

9. Kim, H. P., Imbert, J. and Leonard, W.J. Both integrated and differential regulation of components of the IL-2/IL-2 receptor system. Cytokine Growth Factor Rev, 17:349-366, 2006.

10. Yeh, J.H., Spicuglia, S., Kumar, S., Sanchez-Sevilla, A., Ferrier, P., and Imbert, J. Control of IL-2Ralpha Gene Expression: Structural Changes within the Proximal Enhancer/Core Promoter during T Cell Development. Nucleic Acids Res., 30: 1944-1951; 2002.

11. Lacroix, I., Lipcey, C., Imbert, J., and Kahn-Perles, B. Sp1 activity is upregulated by phosphatase 2A in dividing T lymphocytes. J.Biol.Chem., 277: 9598-9605; 2002.

12. Yeh, J.H., Lecine, P., Nunes, J.A., Spicuglia, S., Ferrier, P., Olive, D. and Imbert, J. Novel CD28-responsive Enhancer Activated by CREB/ATF and AP-1 Families in the Human IL-2Ralpha Locus. Mol.Cell.Biol., 21: 4515-4527; 2001.

13. Rameil, P., Lecine, P., Ghysdael, J., Gouilleux, F., Kahn-Perles, B. and Imbert, J. IL-2 and long-term T cell activation induce physical and functional interactions between STAT5 and ETS transcription factors in human T cells. Oncogene 19: 2086-2097; 2000.

14. Nervi, S., Atlan-Gepner, C., Kahn-Perles, B., Lecine, P., Vialettes, B., Imbert, J. and Naquet, P. Specific deficiency of p56lck expression in T lymphocytes from type 1 diabetic patients. J.Immunol., 165: 5874-5883; 2000.

15. Kahn-Perles, B., Lipcey, C., Lecine, P., Olive, D. and Imbert, J. Temporal and subunit-specific modulations of the Rel/NF-kappa B transcription factors through CD28 costimulation. J.Biol.Chem. 272: 21774-21783; 1997.

16. Lecine, P., Algarte, M., Rameil, P., Beadling, C., Bucher, P., Nabholz, M. and Imbert, J. Elf-1 and Stat5 bind to critical element in a new enhancer of the human interleukin-2 receptor alpha gene. Mol.Cell.Biol. 16: 6829-6840; 1996.

17. Algarte, M., Lecine, P., Costello, R., Plet, A., Olive, D. and Imbert, J. In vivo regulation of interleukin-2 receptor alpha chain gene transcription by the coordinated binding of constitutive and inducible factors in human primary T-cells. EMBO J. 14: 5060-5072; 1995.

18. Pages, F., Ragueneau, M., Rottapel, R., Truneh, A., Nunes, J., Imbert, J. and Olive, D. Binding of phosphatidyl-inositol 3-OH kinase to CD28 is required for T-cell signalling. Nature 369: 327-329; 1994.

19. Costello, R., Lipcey, C., Algarte, M., Cerdan, C., Baeuerle, P.A., Olive, D. and Imbert, J. Activation of primary human T-lymphocytes through CD2 plus CD28 adhesion molecules induces long-term nuclear expression of NF-kappa B. Cell Growth Differ. 4: 329-339; 1993.

20. Imbert, J., Culotta, V.C., Furst, P., Gedamu, L. and Hamer, D. Regulation of metallothionein gene transcription by metals. Adv.Inorg.Biochem. 8: 139-164; 1990.

21. Imbert, J., Zafarullah, M., Culotta, V.C., Gedamu, L. and Hamer, D. Transcription factor MBF-I interacts with metal regulatory elements of higher eucaryotic metallothionein genes. Mol.Cell.Biol. 9: 5315-5323; 1989.

22. Imbert, J., Lawrence, J.-J., Coulier, F., Jeunet, E., Billotey, V. and Birg, F. Cell cycle-dependent expression of early viral genes in one group of simian virus 40-transformed rat cells. EMBO J. 3: 2587-2591; 1984.

23. Imbert, J., Clertant, P., De Bovis, B., Planche, J. and Birg, F. Stabilization of the large T protein in temperature-independent (type A) FR 3T3 rat cells transformed with the simian virus 40 tsA30 mutant. J.Virol. 47: 442-451; 1983.