Michel Cogné, MD, PhD
Birth: May 23rd, 1957 Phone: (33) 555 435 848; Fax: (33) 555 435 897
e-mail: firstname.lastname@example.org Professional address: LAB. of Immunology CNRS UMR 7276, Université de Limoges, 2, Rue Marcland, 87025 LIMOGES France
Sciences: • HDR (research director agreement) (Université de Poitiers, 1991) • PhD in Immunology (under the supervision of Pr. Seligmann, Université Paris VII, 1989) • Master in Biochemistry (Paris VI University, 1984)
Medicine: • Specialty of Biological Medicine: Graduation in Immunology (Université Paris VI, 1983), Graduation in Haematology (Université Paris VII, 1984), Graduation in Microbiology (Université Paris VI, 1985), Graduation in Parasitology (1987) • MD (Université de Poitiers, 1983) Bachelor degree in mathematics (1975, Baccalaureat C, mention Bien)
Current position: • Professor in Immunology, Limoges Medical School (since 1994) • Head of Laboratory of Immunology, Hospital practitioner, Limoges University Hospital (since 1994) • Head of Research Unit UMR CNRS 7276 Control of the immune response and of lymphoproliferation (since 1996), a research unit including 2 teams (i.e. 4 CNRS/INSERM investigators, 10 professors or associate professors, 6 technicians and engineers (including financial staff), 10 PhD students, 4 post-doc) and providing all the necessary resources for molecular immunology, cellular biology and mouse work.
Other professional trainings: • Professor of Biochemistry, University of Poitiers, (1992 -1994) • Investigator (CR1) at the French National Center for Scientific Research (CNRS) (1988-1992) Professional stays abroad: Boston, Harvard Medical School, laboratory of Prof. F.W. Alt (1992-1993) / Montreal, Hospital Notre-Dame, (1981)
ADMINISTRATIVE DUTIES • 2013 - : Chair of Institut Universitaire de France • 2009-2011: President of the Immunology/Haematology commission CN1 from Association Nationale pour la Recherche sur le Cancer (ARC) • 2007-2011: Director of the Federative Research Institute GEIST, IFR 145 (Université de Limoges/ INSERM/CNRS) • Since 2008: Expert at the National Agency for Research Evaluation (AERES) • 1998-2011: Member of the Scientific Council – Université de Limoges • 2005-2008: President of the Scientific Council – Université de Limoges • 2000-2004: Member of the National Center for Scientific Research (CoCNRS) Immunology committee (“commission 25”)
HONORS • 2012-2017: Senior member of Institut Universitaire de France • 1995-2000: Junior member of Institut Universitaire de France • 2001: Laureate of the National Academy of Medicine • 2000: Price Lucien Tartois of the « Fondation pour la Recherche Médicale » • 1996: Price of « Ligue Nationale contre le Cancer »
TEACHING DUTIES • Coordinator of Immunology training courses at the Faculty of Medicine of Limoges. • Coordinator of a Master 2 Immunology teaching unit (Limoges and Clermont-Ferrand Universities) • Coordinator of an Immunology summer school for the Doctoral School of the “Pôle de Recherche et d’Enseignement Supérieur Centre-Atlantique (PRES CA) • Supervision of 11 PhD Students and 5 Master Students over the last 10 years Recent
SUMMARIZED RESEARCH ACTIVITY: My contribution to the field of B cell immunology and immunopathology has yielded about 150 scientific papers (h-index: 27, total number of citations: 2752) and 2 patents (+ 1 pending). The corresponding studies were devoted to the elucidation of immunoglobulin (Ig) gene alterations associated with lymphoproliferative disorders, and to the analysis of the elements regulating Ig gene transcription and recombination in normal B cells, with a special interest into the structural and functional characterization of those regulatory elements lying 3’ of Ig genes. My team thus made important contributions in showing that these elements are strongly involved in all the AID-mediated remodelling events affecting the IgH locus, by regulating germline transcription of Ig genes before class-switch recombination, by regulating somatic hypermutation of IgH V regions and their transcriptional boost in plasma cells, by deregulating those oncogenes that are translocated to the IgH locus due to off-target effects of AID, thus participating to lymphomagenesis, and finally by constituting themselves AID targets and thus promoting locus suicide recombination events. All this work was made possible owing to the unique expertise of the UMR CNRS team that I created in Limoges University, which masters the development of relevant transgenic, knock-out and knock-in mouse models and their analysis and to my strong parallel involvement into basic, clinical and translational research, in collaboration with well-recognized clinical teams. For both basic and clinical projects, my team has indeed set up multiple collaborations and networks with other teams in France and abroad. The team got an A+ mark in its last evaluation by the AERES French agency scoring research, for starting a new contract with CNRS and Limoges University on january 2012.
10-year track-record 10 main scientific original contributions of last 10 years: 1. Khamlichi, A.A., Glaudet F, Oruc Z, Denis V, Lebert M, Cogné M. Immunoglobulin class switch recombination in mice devoid of any Sµ tandem repeat. Blood 2004; 103:3828-36 2. Delpy L, Sirac C, Magnoux E, Duchez S and Cogné M. RNA surveillance contributes to exclusion of nonfunctional genes and detects premature termination within the last exon. Proc. Natl Acad. Sci. USA, 2004a; 101: 7375-7380 3. Delpy L, Sirac C, Le Morvan C, and Cogné M. Transcription-Dependent Somatic Hypermutation Occurs at Similar Levels on Functional and Nonfunctional Rearranged IgH Alleles1. J. Immunol. 2004b;173:1842-8. 4. Reynaud S, Delpy L, Fleury L, Dougier HL, and M Cogné. Interallelic class switch recombination significantly contributes to class switching in mouse B cells. J. Immunol 2005; 174:6176-6183 5. Sirac C., Carrion C., Duchez S., Comte I., and Cogné M. Light chain inclusion permits terminal B cell differentiation and does not necessarily promote autoreactivity without promoting autoreactivity Proc. Natl Acad. Sci. USA 2006; 103:7747-52 6. Sirac C, Bridoux F, Carrion C, El Hamel JC, Aldigier G, Touchard M, and Cogné M Role of the monoclonal chain V domain and reversibility of renal damage in a transgenic model of acquired Fanconi’s syndrome. Blood 2006; 108:536-43 7. Gostissa M, Yan CT, Bianco JM, Cogné M, Pinaud E, Alt FW. Long-range oncogenic activation of Igh-c-myc translocations by the Igh 3' regulatory region. Nature 2009, 462: 803-7 8. Duchez S, Amin R, Cogné N, Sirac C, Delpy L, Pascal V, Corthésy B, and Cogné M. Premature expression of α Ig heavy chains delays B cell differentiation and promotes plasma cell maturation. Proc Natl Acad Sci USA. 2010; 107: 3064-9 9. Péron S, Laffleur B, Denis N, Cook-Moreau J, Tinguely A, Delpy L, Denizot Y, Pinaud E, Cogné M. Immunoglobulin heavy chain locus suicide recombination in mature B cells. Science 2012; 336: 931-4 10. Rouaud P, Vincent-Fabert C, Saintamand A, Fiancette R, Marquet M, Robert I, Reina-San-Martin B, Pinaud E, Cogné M*, Denizot Y* (*co-senior authors) The IgH 3’ regulatory region controls somatic hypermutation in germinal centre B-cells J Exp Med 2013. 210: 1501-1507DOI: 10.1084/jem.20130072
2. Recent chapters of books and reviews: • Cogné M and B.K., Birshtein “ Regulation of class switch recombination » in « Molecular biology of B cells ». T. Honjo, M.S. Neuberger and F.W. Alt eds, Elsevier Academic press, 2004 • Pinaud E, Marquet M, Fiancette R, Péron S, Vincent-Fabert C, Denizot Y, Cogné M. The IgH locus 3’ regulatory region : pulling the strings from behind. Advances in Immunology 2011; 110:27-70 • Laffleur B, Pascal V., Sirac C, Cogné M. Production of human or humanized antibodies into mice. Methods in molecular biology 2012 , 901:149-59 3.
• WO2005047333 (2005) NON-HUMAN TRANSGENIC MAMMAL FOR THE CONSTANT REGION OF THE CLASS A HUMAN IMMUNOGLOBULIN HEAVY CHAIN AND APPLICATIONS THEROF by COGNE Michel et al (under active license to B Cell Design)
• French patent :- 08/00319 (registered in France on february 22, 2008 by Université de Limoges / CNRS) : Cogné Michel et al: « Transgenic non human mammal for the gamma 1 class constant region of human immunoglobulin heavy chain and applications therof» (under license to B Cell Design)
• Cogné Michel et al: “Transgenic non-human mammal for producing chimeric human immunoglobulin E antibodies”. European patent request under examination # HLP/clp-F249800001/EP/OEB, NB: These patents and additional work currently under application for an additional patent led to the creation of a spin-off company of our CNRS unit (“B cell Design”), run by former post-docs of the lab.
4. Meetings / Recent invited oral presentations:
• 8th International Congress on Recombinant Antibodies, Dublin, June 24-26, 2008 "Immunoglobulin A: for research and therapeutic applications” • IQPC meeting on Therapeutic antibodies, London, Sept 30th-Oct 1st, 2009, “Applying Cutting-Edge Antibody Engineering For the Development of New Generation of Humanised Antibodies » • 9th International Congress on Recombinant Antibodies. Berlin, Germany. June 14-18, 2010, “Production of IgA antibodies and their variants. » • 1st French Lymphoma Workshop, Rennes, 20-21 janvier 2011 “Modèles murins d’étude mutationnelle du locus IgH et lymphomogenèse”. • ACCITH Meeting “Antibodies and therapeutic targeting", Strasbourg, September 19-21, 2011, "In vitro and in vivo evaluation of anti-CD20 antibodies shows the IgA class to surpass IgG for direct effect on target cells.” • International meeting on “B cells and Antibodies”, Jerusalem, October 23-26, 2011,“Regulation of immunoglobulin expression in mature B cells” • Keystone meeting “Mutations, Malignancy and Memory”, Boston, March 18-21, 2012, ,“Locus suicide recombination in mature B cells” • Symposium “Allelic gene regulation in health and disease”, Toulouse, February 11-12, 2013, "Immunoglobulin genes in mature B cells: from biallelic accessibility to monoallelic expression” • 3rd Workshop on Normal and neoplastic B cells. Oléron, France, September 19-22, 2013 Michel Cogné “Modulation of B cell fate upon AID-mediated Ig gene recombination” • "Fédération de Médecine Translationnelle de Strasbourg" (FMTS), 4 décembre 2013, Strasbourg. Michel Cogné. « Régulation de la survie des lymphocytes B mémoires et implications cliniques » • Symposium “Antibodies: the good, the bad, and the promising”; VU University Medical Center, AMSTERDAM, Feb 5th, 2014, Michel Cogné: “Control of B cell fate after AID-mediated modulation of BCR expression” • French Hematology Society 2014 congress. Paris La Défense (2014, march 27-29). M. Cogné “BCR expression and B Cell Fate” • Henry Kunkel Society’s 22nd Annual Meeting, “Human Immunology in Health and Disease” the Rockefeller University, New York, April 3-5, 2014. Michel Cogné “B cells switching to deadly paths”. • European Hematology Association 2014 congress. Milan (june 12-15). M. Cogné “Class-switch recombination: theme with variations” • European Association for Haematopathology (EAHP) 2014 Meeting, Istanbul, Turkey, Oct 17-22. M. Cogné: “Immunology of normal B cell differentiation” Conference chairs: • International meeting on “B cells and Antibodies”, Jerusalem, October 23-26, 2011 • Keystone meeting “Mutations, Malignancy and Memory”, Boston, March 18-21, 2012, Meeting organization: « 1st European workshop on IgA in health and pathology. » Limoges, France, 2006, may 17-18 5. Recent prize: • September 2012: elected senior member of Institut Universitaire de France (2012-2017)
6. Contribution to early careers of excellent scientists
• Amine Khamlichi, first PhD (1993) and later CNRS investigator (until 2006) under my supervision, now a CNRS research director in Toulouse, • Eric Pinaud, PhD 2001 under my supervision, now CNRS CR1 investigator in Limoges • Laurent Delpy, PhD 2002 under my supervision, now CNRS CR1 investigator in Limoges • Christope Sirac, PhD 2003 under my supervision, now an associate professor in Limoges University, • Stephane Reynaud, post-doc 2004-6 under my supervision, now assistant professor, Grenoble University • Sophie Duchez, former PhD under my supervision (PhD 2007), currently CNRS research engineer in Paris • Yves Denizot, having joined my team in 2000 as an INSERM investigator and now starting his own team in the lab as an INSERM research director since 2012 • Sophie Péron, post-doc 2010-13 under my supervision, now INSERM investigator, Limoges University
7. Main scientific achievements: • setting up mouse models of Ig deposition diseases (Rengers et al, 2000, Sirac et al 2006a) • first showing that 3 IgH enhancers control class switch recombination through regulation of accessibility and germline transcription, and first revealing the conserved global structure of the 3’ IgH regulatory region as a large palindrome in rodents and human (Cogné et al, 1994, Chauveau et al, 1996, Pinaud et al, 1998, Pinaud et al, 2001, Truffinet et al, 2007, Bebin et al, 2008, Vincent et al, 2010) and control somatic hypermutation at the IgH locus (Rouaud et al, 2013). • contributing original models to the study of allelic and light chain exclusion, and interallelic recombination (Delpy et al, 2004a and 2004b, Reynaud et al, 2005, Sirac et al 2006b) • discovering the process of Locus Suicide Recombination mediated by AID in mature B cells and resulting in loss of BCR expression and consecutive B cell apoptosis (Péron et al, 2012) • setting up models for the basic study of IgA producing cells (Duchez et al, 2010, Amin et Al, 2012) and mouse models for the fast production in humanized class-switched monoclonal antibodies (Patent WO2005047333, 2005, French patent 08/00319, 2008) and showing the efficacy of anti-CD20 IgA antibodies, (Pascal et al, 2012).
see PUBMED and http://hal.archives-ouvertes.fr/CRIBL
F. Denis, M. Cogné, Belec L. « Femme enceinte et défense immunitaire anti-virale. » Dans :” les virus transmissibles de la mère à l’enfant”, Med/Sci, John Libbey, Paris 1999, pp24-56. Cogné M. « Immunité humorale. Lymphocytes B ; immunoglobulines (structure, fonction, diversité ; investigation clinique ; concept de déficit inné de l’immunité humorale). » Rev Prat. 2001 Jan 31;51(2):193-202 Cogné Michel, GALEA Horia Radhu, SIRAC Christophe and DECOURT Catherine « Immunoglobulin decreased solubility diseases: pathologies of the V domains?” in ‘Monoclonal gammopathies and the kidney” Karger press, G. Touchard and P. Ronco eds, 2002, Cogné M and B.K., Birshtein “ Regulation of class switch recombination » in « Molecular biology of B cells ». T. Honjo, M.S. Neuberger and F.W. Alt eds, Elsevier Academic press, 2004 Cogné M. La saga des immunoglobulines: des protéines aux millions de formes. Microscoop 2003 Delpy L, Sirac C et Cogné M. Le silence des allèles exclus… et la surveillance non canonique des ARNm d’immunoglobulines. SFI Actualités. Juin 2004, 107 : p9-10. Cogné M and B.K., Birshtein “ Regulation of class switch recombination » in « Molecular biology of B cells ». T. Honjo, M.S. Neuberger and F.W. Alt eds, Elsevier Academic press, 2004 Cogné M. « Immunoglobulines monoclonales ». Rev Prat. 2004 May 15;54(9):1019-24) Cogné M. Chapître 4 , “Immunosénescence” dans « Vieillissement : les données biologiques » » Ed F. Denis. Elsevier, 2005. Bridoux F, Sirac C, Jaccard A, Ayache RA, Goujon JM, Cogné M and Touchard G. Renal Disease in cryoglobulinemic vasculitis. In « The Kidney in systemic autoimmune diseases. JC Mason and CD Pusey eds, pp216-240. Elsevier. 2008. Cogné M, Duchez S, Pascal V. Transgenesis and humanization of murine antibodies. Médecine / Sciences (Paris). 2009, 25:1149-54 C. Sirac, F. Bridoux, M. Essig, O. Devuyst, G. Touchard and M. Cogné. Toward understanding renal Fanconi syndrome: step by step advances through experimental models. In “ Experimental models for Renal Disease: Impact on Understanding Pathogenesis and improving Diagnosis”, Herrera GA. Eds Karger AG-Medical and Scientific Publishers Contrib Nephrol. 2011;169:247-61 Pinaud E, Marquet M, Fiancette R, Péron S, Vincent-Fabert C, Denizot Y, Cogné M. The IgH locus 3’ regulatory region : pulling the strings from behind. Advances in Immunology 2011; 110:27-70 Laffleur B, Pascal V., Sirac C, Cogné M. Production of human or humanized antibodies into mice. Methods in molecular biology 2012 , 901:149-59 Pascal V, Laffleur B. and Cogné M. Class-specific effector functions of therapeutic antibodies. Methods in molecular biology 2012;901:295-317 Péron S, Laffleur B, Denis-Lagache N, Cook-Moreau J, Filloux M, Cogné M. IgH locus suicide recombination or When B cells surrender ! Médecine / Sciences (Paris). 2012, 28 : 551-4
Pr. Michel Cogné, MD, PhD, studied immunoglobulin (Ig) gene alterations in human disorders and transcriptional regulation of Ig genes, successively in the Universities of Paris 6, Poitiers, Harvard and Limoges. He contributed unravelling the gene alterations in heavy chain diseases and connected them with aberrations in V(D)J recombination, somatic hypermutation and class switching. He first showed that 3’ IgH enhancers control class switching and revealed the conserved palindromic structure of the 3’ IgH regulatory region (Cogné et al, 1994, Chauveau et al, 1996, Pinaud et al, 1998 and 2001, Wuerffel, 2007). His team showed the role of 3’ IgH enhancers in lymphomagenesis (Truffinet 2007, Gostissa, 2010), somatic hypermutation (Rouaud, 2013) and in a recently reported B cell death pathway through IgH locus suicide recombination (Péron 2012). He also set up models of light chain deposition diseases (Khamlichi 1995, Decourt 1999, Rengers 2000, Sirac 2006), and contributed original models of allelic exclusion, interallelic switching, class-switched BCR function (Delpy 2004, Reynaud 2006, Sirac 2006, Duchez 2010, Laffleur, 2014).