CV Science

Michel Cogné MD PhD Immunology / Immunogenetics

Course and current status

Michel Cogné, MD, PhD

Birth: May 23rd, 1957

e-mail: michel.cogne@inserm.fr Professional address: LAB. of Immunology / B-cell & Ig Gene remodeling Singularities (BIgReS), Inserm U1236, Faculté de Médecine, 35000 RENNES

EDUCATION

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)

PROFESSIONAL ACTIVITIES

Current position: • Professor in Immunology, Rennes Medical School (since 2020), Limoges Medical School (1994-2020) • Head of Research Team BIGReS, as part of unit Inserm 1236, Rennes University • Former head of Research Unit UMR CNRS 7276 Control of the immune response and of lymphoproliferation (1996-2020).

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)

INSTITUTIONAL RESPONSABILITIES
• 2022- member of the INSERM scientific council
• 2016-2021 President, INSERM committee CSS5 (Immunology / microbiology)
• 2013-2018 Chair of Institut Universitaire de France, Paris, France
• 2007-2011 Director of Research Institute GEIST (Université de Limoges/ INSERM/CNRS)
• 1998-2011 Member and president 2005-2008 of  the Scientific Council – Limoges University

AWARDS
• 2018 « Honor team » from Association pour la Recherche sur le Cancer (ARC)
• 2015 Research Prize of Fondation ALLIANZ / Institut de France
• 2014 Bourse d’Immunologie Fondation CSL Behring
• 2012-2018 (senior) and 2000-1995 (junior) member of Institut Universitaire de France
• 2001: Laureate of the National Academy of Medicine
• 2000 : Prize Lucien Tartois of the « Fondation pour la Recherche Médicale »
• 1996 : Prize of « Ligue Nationale contre le Cancer »

SUPERVISION OF GRADUATE STUDENTS AND POSTDOCTORAL FELLOWS
Recent post-docs : Brice Laffleur (2020-2021), Alexis Saint-Amand (2018-2019), Julie Garrier (2017-2019), Marie Marquet (2016-2017), Sandrine Le Noir (2015-2017),

Recent PhD students :
• 2020-            Ophélie Dèze, Rennes University
• 2018-2022     Natsuko Ueda, Rennes University (co-direction with Pr. G. Semana)
• 2018-2022     Marine Cahen, Limoges University (co-direction with Dr. C. Sirac)
• 2018-2021.    Lina Zaweel, (co-direction with K. Tarte)
• 2015-2019     Zeinab Dalloul, Limoges University
• 2015-2019     Iman Dalloul, Limoges University
• 2015-2019     Batoul Webbi, Limoges University (co-direction with Pr. JC Aldigier)
• 2013-2017     Nicolas Denis-Lagâche, Limoges University
• 2012-2015     Brice Laffleur, Limoges University
• 2010-2013     Ahmed Boumediene, Limoges University
• 2009-2012     Virginie Pascal, Limoges University
• 2008-2011     Sophie Duchez, Limoges University
TEACHING DUTIES
• Contribution of Immunology courses for MD students and Master students (Rennes, Limoges Universities)

REVIEWING ACTIVITY
• 2016-2021   President, national INSERM committee “Immunology and Microbiology” (CSS5)
• 2009-2019   Evaluator, National Agency of Research (ANR) & Institut National du Cancer (INCa)
• 2009-2019   Panel member, Haut Comité d’évaluation de la recherche scientifique (HCERES) (notably President of the 2012 Review board for the Institute « Imagine » headed by Pr. A. Fisher, Paris, France / President of the 2020 Review board of the team headed by Pr. G. Salles, Cancer Research Center, Lyon, France)
• 2018    member, Scientific Advisory Board, Cancer Center, Toulouse University, France
• 2013-2018       Member, scientific council of the Fondation de la Recherche Médicale
• 2017     Review panel member, Immunology committee, The Academy of Finland, Helsinki
• 2011-2016      Evaluator,  Associazione Italiana per la Ricerca sul Cancro (AIRC), Italy
• 2010-2012      President, Immunology committee, Association Recherche sur le Cancer (ARC)
RESEARCH FOCUS
My contribution to B cell immunology and immunopathology has yielded about 200 scientific papers (h-index 41) and 5 patents (3 under active license). These studies were first devoted to the elucidation of Ig gene alterations associated with lymphoproliferative disorders, notably heavy chain diseases and Ig deposition diseases standing as complications of monoclonal gammopathies, I am also specially committed to the analysis of the elements regulating Ig gene transcription and recombination, with a focus on the regulatory elements lying 3’ of Ig gene loci. This brought me to explore the class-specific functions impacted into B cells by AID-mediated expression of switched IgA or IgE BCR molecules.
We specially studied the role of the IgH 3’RR with regards to AID-mediated remodelling events affecting the locus, boosting IgH  transcription in plasma cells, and deregulating oncogenes translocated to the IgH locus, thus participating into lymphomagenesis.
Besides developing transgenic, KO and knock-in models, pertinent to B cell immunology and lymphomagenesis, I was involved into translational research, in collaboration with clinicians.
My unit, scored A+ in its last evaluation, is strengthened by having encouraged young investigators as senior or co-senior authors even when funded and guided by the team director.
Main scientific achievements hereby:
• setting up mouse models of Ig deposition diseases (Rengers et al, Blood, 2000, Sirac et al, Blood, 2006, Bonaud et al, Blood, 2015) and a national referral center for Ig deposition diseases
• showing that the IgH 3’RR controls CSR through accessibility regulation  and germline transcription (Cogné et al, Cell, 1994, Pinaud et al, Immunity, 2001, Vincent-Fabert et al, Blood, 2010), and also controls SHM (Rouaud et al, J Exp Med, 2013);
• revealing the conserved palindromic architecture of the IgH 3’RR and its functional role (Chauveau et al, Nat. Genetics, 1996, Saintamand et al, Nat. Comm 2016, Le Noir et al, 2017)
• showing that AID-targeted S regions are not sufficient for CSR (Bonaud et al, Nat Comm 2015)
• contributing models to study allelic and light chain exclusion and interallelic CSR (Delpy et al, PNAS, 2004; Reynaud, J Immunol 2005; Sirac  PNAS, 2006, Laffleur, Genes & Immunity, 2013)
• setting up models of IgA producing cells (Duchez et a, PNAS l, 2010, Oruc et al, JASN. 2016) & production of humanized class-switched mAbs (Patents WO2005047333, & 08/00319, 2008), and showing the efficacy of anti-CD20 IgA antibodies, (Pascal et al,  Haematologica, 2012).
• discovering AID-mediated Locus Suicide Recombination mediated with BCR loss and consecutive B cell apoptosis (Péron et al, Science, 2012, Dalloul et al, Plos Genet, 2019)
• describing other B-lineage negative selection pathways (Death pathways induced by IgE BCR expression (Laffleur et al, Cell Reports, 2015) / the “TIE-checkpoint”, a late quality control killing cells producing truncated Ig encoded by non-functional alleles (Srour et al, J Exp Med, 2016)
MEMBERSHIPS OF SCIENTIFIC SOCIETIES
•    2012 –     Member, Henry Kunkel Society, Rockefeller Institute, USA
•    2012 –     Member, British Society for Immunology
•    1992 –     Member, French Society for Immunology
PUBLICATION RECORD

see PUBMED and http://hal.archives-ouvertes.fr/CRIBL

BOOK CHAPTERS:

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

Scientific summary

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).