CV Science

Laurent CORCOS PhD Biomedical Research

Course and current status

INSERM U1078-ECLA team

Faculty of Medicine,

22 Avenue Camille Desmoulins

29200 BREST, FRANCE                                                                                  

 

Diplomas and academic cursus

1988: PhD (Paris VI, Pasteur Institute, supervisor:Dr MC Weiss)

1990: INSERM Position 

1990-1992: Post-doctoral training (McArdle Laboratory for Cancer Research, Madison, WI, USA, supervisor: Pr N. Drinkwater)

1995: CESAM diploma (Statistics applied to medicine)

1997: Research Directorship

2006: Inserm Research Director 

 

10/1992-12/1998: Inserm Unit 49, then Unit 456 (Rennes) 

01/1999-08/2004: Inserm Unit 517 (Dijon)

09/2004-12/2011: Inserm Unit 613 (Brest)

01/2012- : Inserm Unit 1078 (Brest)      

 

University teaching (Rennes, Dijon, Brest)

Master’s level: Pharmacology, Toxicology, Cell death, Cancer 

 

Member of scientific steering and evaluation committees  

School of Pharmacy, Rennes (1996-1998)

National Institute for Agronomical Sciences (INRA) Nutrition-Toxicology (2004-2010)

Member of INSERM committee 8 Nutrition-Toxicology (1998-2002)

Member of INSERM committee 4 Chemistry-Biology (1998-2002)

Member of University committees (64, 65, 66, 69) Biochemistry and Molecular Biology (2000-2004)

Member of the INSERM Scientific Council (2004-2008)

Scientific Director of the council of the Federative Institute 100 (2002-2004)

Vice President of the Research Association against Cancer (ARC) “Grand Ouest” (2006-2010)

Member of C.RIS Pharma Scientific committee (2004- )

Member of the administration board of Biogenouest (2004- )

Member of the administration board of the CRITT (Id2) Santé Bretagne (2006-2015)

Director of « Structure Fédérative de Recherche » ScInBioS (2012-2017)

Director of the « Institut Brestois de Santé Agro Matière » (2017- )

Member of the INSERM Scientific Council (2013-20017)

 

Consulting

Oncodesign^SA, Dijon (1999-2004)

C.RIS Pharma, St Malo (2004- )

DEBIOPHARM, Lausanne (2015-2017) 

Selected publications 

0: Goulitquer S, Croyal M, Lalande J, Royer AL, Guitton Y, Arzur D, Durand S, Le Jossic-Corcos C, Bouchereau A, Potin P, Akoka S, Antignac JP, Krempf M, Ferchaud-Roucher V, Giraudeau P, Corcos L. Consequences of blunting the mevalonate pathway in cancer identified by a pluri-omics approach. Cell Death and Disease, 2018,in press.

1: Durand S, Trillet K, Uguen A, Saint-Pierre A, Le Jossic-Corcos C, Corcos L. A transcriptome-based protein network that identifies new therapeutic targets incolorectal cancer. BMC Genomics. 2017 Sep 30;18(1):758. doi:10.1186/s12864-017-4139-y. PubMed PMID: 28962550; PubMed Central PMCID:PMC5622428.

2: El Khoury F, Corcos L, Durand S, Simon B, Le Jossic-Corcos C. Acquisition ofanticancer drug resistance is partially associated with cancer stemness in human colon cancer cells. Int J Oncol. 2016 Dec;49(6):2558-2568. doi:10.3892/ijo.2016.3725. Epub 2016 Oct 7. PubMed PMID: 27748801.

3: Gattolliat CH, Uguen A, Pesson M, Trillet K, Simon B, Doucet L, Robaszkiewicz M, Corcos L. MicroRNA and targeted mRNA expression profiling analysis in humancolorectal adenomas and adenocarcinomas. Eur J Cancer. 2015 Feb;51(3):409-20.doi: 10.1016/j.ejca.2014.12.007. Epub 2015 Jan 10. PubMed PMID: 25586944.

4: Dujardin G, Lafaille C, de la Mata M, Marasco LE, Muñoz MJ, Le Jossic-CorcosC, Corcos L, Kornblihtt AR. How slow RNA polymerase II elongation favorsalternative exon skipping. Mol Cell. 2014 May 22;54(4):683-90. doi:10.1016/j.molcel.2014.03.044. Epub 2014 May 1. PubMed PMID: 24793692.

5: Pesson M, Volant A, Uguen A, Trillet K, De La Grange P, Aubry M, Daoulas M,Robaszkiewicz M, Le Gac G, Morel A, Simon B, Corcos L. A gene expression andpre-mRNA splicing signature that marks the adenoma-adenocarcinoma progression in colorectal cancer. PLoS One. 2014 Feb 6;9(2):e87761. doi:10.1371/journal.pone.0087761. eCollection 2014. PubMed PMID: 24516561; PubMedCentral PMCID: PMC3916340.

6: Pesson M, Eymin B, De La Grange P, Simon B, Corcos L. A dedicated microarrayfor in-depth analysis of pre-mRNA splicing events: application to the study ofgenes involved in the response to targeted anticancer therapies. Mol Cancer. 2014Jan 15;13:9. doi: 10.1186/1476-4598-13-9. PubMed PMID: 24428911; PubMed CentralPMCID: PMC3899606.

7: Corcos L, Le Jossic-Corcos C. Statins: perspectives in cancer therapeutics.Dig Liver Dis. 2013 Oct;45(10):795-802. doi: 10.1016/j.dld.2013.02.002. Epub 2013Mar 13. Review. PubMed PMID: 23490341.

8: Follet J, Corcos L, Baffet G, Ezan F, Morel F, Simon B, Le Jossic-Corcos C.The association of statins and taxanes: an efficient combination trigger ofcancer cell apoptosis. Br J Cancer. 2012 Feb 14;106(4):685-92. doi:10.1038/bjc.2012.6. Epub 2012 Jan 31. PubMed PMID: 22294184; PubMed CentralPMCID: PMC3322964.

9: Follet J, Rémy L, Hesry V, Simon B, Gillet D, Auvray P, Corcos L, LeJossic-Corcos C. Adaptation to statins restricts human tumour growth in Nudemice. BMC Cancer. 2011 Nov 22;11:491. doi: 10.1186/1471-2407-11-491. PubMed PMID:22107808; PubMed Central PMCID: PMC3254125.

10: Dutertre M, Sanchez G, Barbier J, Corcos L, Auboeuf D. The emerging role ofpre-messenger RNA splicing in stress responses: sending alternative messages and silent messengers. RNA Biol. 2011 Sep-Oct;8(5):740-7. doi: 10.4161/rna.8.5.16016.Epub 2011 Jun 29. Review. PubMed PMID: 21712650.

11: Tixier F, Le Rest CC, Hatt M, Albarghach N, Pradier O, Metges JP, Corcos L,Visvikis D. Intratumor heterogeneity characterized by textural features onbaseline 18F-FDG PET images predicts response to concomitant radiochemotherapy inesophageal cancer. J Nucl Med. 2011 Mar;52(3):369-78. doi:10.2967/jnumed.110.082404. Epub 2011 Feb 14. PubMed PMID: 21321270; PubMedCentral PMCID: PMC3789272.

12: Dutertre M, Sanchez G, De Cian MC, Barbier J, Dardenne E, Gratadou L,Dujardin G, Le Jossic-Corcos C, Corcos L, Auboeuf D. Cotranscriptional exonskipping in the genotoxic stress response. Nat Struct Mol Biol. 2010Nov;17(11):1358-66. doi: 10.1038/nsmb.1912. Epub 2010 Oct 24. PubMed PMID:20972445.

13: Dujardin G, Buratti E, Charlet-Berguerand N, Martins de Araujo M, Mbopda A,Le Jossic-Corcos C, Pagani F, Ferec C, Corcos L. CELF proteins regulate CFTRpre-mRNA splicing: essential role of the divergent domain of ETR-3. Nucleic AcidsRes. 2010 Nov;38(20):7273-85. doi: 10.1093/nar/gkq573. Epub 2010 Jul 14. PubMedPMID: 20631008; PubMed Central PMCID: PMC2978352.

Scientific summary

I obtained my PhD from the Pasteur Institute (1988). I studied liver differentiation with the Reuber rat hepatoma cell system. I followed with studies aimed at analysing the regulation of expression of detoxication enzymes, such as cytochromes P450, by Phenobarbital and dexamethasone (1986-1993). We were the first to show that the antiprogestin RU486 mimicked the inductive effect of Phenobarbital in hepatoma cells. It was later shown that this effect was due to activation of two nuclear receptors, the Constitutive Androstane Receptor (CAR) or the Pregnane X Receptor (PXR).

Then I studied the interaction between inflammatory mediators, like IL1b, IL6, TNFa or TGFb, or anti-inflammatory cytokines like IL4 (1993-1996). We showed that the pro-inflammatory cytokines reduced cytochrome P450 expression in human hepatocytes, whereas IL4 was unique in inducing cytochrome P4502E1, the ethanol-inducible enzyme. We also cloned several mouse cytochromes P450 from the 2b family, and showed, by a genetic analysis in mice, that Phenobarbital induction of cytochrome P4502b10 was regulated by one major chromosomal locus (1995-1998). Recently, we also got involved in the study of human cytochromes P4504A and 4F, among others, using the liver hepatoma cell line HepaRG, both from a biochemical and biological perspective (2006-2009).

I also studied apoptosis in human cells and we were the first group to clone the human Caspase-2 gene (before the availability of the human genome sequence), and went on to describe its transcriptional regulation as well as the regulation of its alternative pre-mRNA splicing brought about by DNA damaging agents (2003-2008). We also showed that caspase-2 played a role independent of its activity in apoptosis, in lipid anabolism through its regulation by Sterol Regulatory Element Binding Proteins (SREBP). We also showed that human caspase-7 was also regulated by lipid levels, through SREBP (2009).

We also built the first bioinformatics model of the cholesterol synthesis pathway using Boolean equations and an adaptation of Markov chains (2008).

We studied alternative pre-mRNA splicing of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, and showed that the ETR-3 splice protein, which was known to be active mainly in muscles, was a novel regulator of CFTR pre-mRNA splicing in epithelial cells (2010).

We also studied the effect of DNA damaging agents on the coupling between transcription and pre-mRNA splicing, and we showed that the molecular dialogue between both machineries involved YB1and EWS (2010). The interaction was disrupted upon DNA damage, which led to a profound modification of the splicing machinery, with a rather massive effect on MDM2 alternative pre-mRNA splicing.

We now follow two main paths: firstly, we survey apoptosis endpoints as a response to blunting the mevalonate (cholesterol) pathway. Secondly, we perform large-scale analyses of alternative pre-mRNA splicing using Exon Array gene chips in human digestive tract diseases. We will then integrate all these data with the aim to model the associated events in human cancer.