Research director CNRS
Team leader BioPIC
Research activities are concerned with the regulation of the expression of Immunoglobulins and are centered around 3 axes:
– degradation of Ig transcripts by NMD (nonsense-mediated mRNA decay),
– alternative splicing of Ig genes and impact of incomplete Ig,
– aberrant Ig production by exon skipping approaches using antisense oligonucleotides
Office 210 CBRS
05 19 56 42 14
Research
The main objective of the research projects is to analyze RNA surveillance and alternative splicing of immunoglobulin transcripts, in order to assess the impact of aberrant Ig chains during normal or pathological B development. Our recent work has revealed that an exon skipping phenomenon results in the production of Ig chains without a variable domain (V). Interestingly, these aberrant Ig cause cell stress and induce apoptosis of plasma cells (Srour et al, J Exp Med 2016). This discovery opens up new prospects for therapeutic exon skipping in the treatment of plasma cell pathologies such as myeloma (patent WO2017 / 089359). Current projects thus have a fundamental research component (ANR projects, ARC Foundation, Ligue Contre le Cancer, etc.) and a valuation component (SATT maturation program).
Training
2nd year Master (Immunology Module), Theme: Transcriptional accessibility of Ig genes and allelic exclusion phenomena
1st year Master, Limoges, Theme: Regulation of gene expression
2012-2017 : Member of the Board of the Doctoral School of Bio-Health (ED 524)
Education
Since 10/2017 : Research director CNRS 2nd class (DR2) (CNRS U7276 – INSERM U1262, CRIBL, Limoges)
12/2010 : Authorization to supervise research
10/2009 : Permanent researcher CNRS 1st class (CR1) (UMR CNRS 6101, Limoges)
02/2009 : Level I animal experimentation accreditation (Bordeaux)
10/2005-10/2009 : Permanent researcher CNRS 2nd class (CR2) (UMR CNRS 6101, Limoges)
09/2002-10/2005 : Post-doctoral researcher (INSERM U563 team Dr J-C. Guéry, Toulouse)
2001-2002 : ATER University of Limoges
1998-2002 : PhD student B(UMR CNRS 6101, supervised by Pr. M. Cogné, Limoges)
Skills
Immunology, Genetics of immunoglobulins, RNA biology…
Representative publications
1- Srour N, Chemin G, Tinguely A, Ashi MO, Péron S, Oruc-Ratinaud Z, Sirac C, Cogné M, Delpy L. A plasma cell differentiation quality control ablates B cell clones with biallelic Ig rearrangements and truncated Ig production. J Exp Med. 2016 Jan 11; 213(1): 109–122.
2- Bonaud A, Bender S, Touchard G, Lacombe C, Srour N, Delpy L, Oblet C, Druilhe A, Quellard N, Javaugue V, Cogné M, Bridoux F, Sirac C. A mouse model recapitulating human monoclonal heavy chain deposition disease evidences the relevance of proteasome inhibitor therapy. Blood. 2015 Aug 6;126(6):757-65.
3- Péron S, Laffleur B, Denis-Lagache N, Cook-Moreau J, Tinguely A, Delpy L, Denizot Y, Pinaud E, Cogné M. AID-Driven Deletion Causes Immunoglobulin Heavy Chain “Locus Suicide Recombination” in B Cells. Science 2012 May 18;336(6083):931-4.
4- Tinguely A, Chemin G, Péron S, Sirac C, Reynaud S, Cogné M, Delpy L. Crosstalk between IgH transcription and RNA surveillance during B cell development. Mol Cell Biol 2012 Jan;32(1):107-17.
5- Chemin G, Tinguely A, Sirac C, Lechouane F, Duchez S, Cogné M, Delpy L. Multiple RNA surveillance mechanisms cooperate to reduce the amount of nonfunctional Ig kappa transcripts. J Immunol 2010 May 1;184(9):5009-17.
6- Duchez S, Amin R, Cogné N, Delpy L, Sirac C, Pascal V, Corthésy B, Cogné M. Premature replacement of mu with alpha immuglobulin chains impairs lymphopoiesis and mucosal homing but promotes plasma cell maturation. Proc Natl Acad Sci U S A 2010 Feb 16;107(7):3064-9.
7- Billon-Galés A, Fontaine C, Douin-Echinard V, Delpy L, Berges H, Calippe B, Lenfant F, Laurell H, Guéry JC, Gourdy P, Arnal JF. Endothelial estrogen receptor-alpha plays a crucial role in the atheroprotective action of 17beta-estradiol in low-density lipoprotein receptor-deficient mice. Circulation 2009 Dec 22;120(25):2567-76.
8- Delpy L, Douin-Echinard V, Garidou L, Bruand C, Saoudi A, Guéry JC. Estrogen enhances susceptibility to experimental autoimmune myasthenia gravis by promoting type 1-polarized immune responses. J Immunol 2005 Oct 15;175(8):5050-7.
9- Delpy L, Sirac C, Le Morvan C, Cogné M. Transcription-dependent somatic hypermutation occurs at similar levels on functional and nonfunctional rearranged IgH alleles. J Immunol 2004 Aug 1;173(3):1842-8.
10- Delpy L, Sirac C, Magnoux E, Duchez S, Cogné M. RNA surveillance down-regulates expression of nonfunctional kappa alleles and detects premature termination within the last kappa exon. Proc Natl Acad Sci U S A 2004 May 11;101(19):7375-80.
11- Delpy L, Le Bert M, Cogné M, Khamlichi AA. Germ-line transcription occurs on both the functional and the non-functional alleles of immunoglobulin constant heavy chain genes. Eur J Immunol 2003 Aug;33(8):2108-13.
12- Delpy L, Decourt C, Le Bert M, Cogné M. B cell development arrest upon insertion of a neo gene between JH and Emu: promoter competition results in transcriptional silencing of germline JH and complete VDJ rearrangements. J Immunol 2002 Dec 15;169(12):6875-82.
Distinctions
Since 2017 : Fondation ARC, member of the National Commission 1 (CN1: Immunologie, onco-hématologie, microbiologie)
Since 2016 : Ligue Contre le Cancer, member of trhe scientific council of La Ligue contre le Cancer Aquitaine
Since 2012 : Member of the scientific council of CORC (Comité d’Orientation de la Recherche sur le Cancer en Limousin)
2011-2017 : Cancéropôle GSO, member Steering committee (axis 2)