Christophe Sirac



Professeur des Universités
Responsable de l’équipe BioPIC

My research activity is devoted to the regulation of immunoglobulin (Ig) expression and production in normal and pathogenic situations. I contributed to elucidation of the pathophysiology of monoclonal Ig related diseases using experimental models

Bureau 210 CBRS
05 19 56 42 13


Education

1998-1999 Master’s degree in immunology with honours (University of Poitiers, France)
1999-2003 PhD in Immunology (University of Limoges, France) : “Concerted regulation of immunoglobulin chain expression and consequences in pathology” (Director Michel Cogné, CNRS UMR 6101)
2016 HDR (French Habilitation to Conduct researches): “Late maturation of B cells and pathogenicity of monoclonal immunoglobulins”

 

Positions

2003-2004 Assistant professor, University of Limoges, France
2004-2006 Research assistant, LFB Biotech (French biotech company), Lille, France (optimization of cell lines for the production of therapeutic antibodies)
2006-2018 Associate professor, University of Limoges, France
2019-present Professor, University of Limoges, France

 

Teaching activities, tutoring and memberships

– 2018-2022 In charge of the “Biology and Health Science” master programs at Limoges University
– 2008-2018 Head of the Master program « Biotechnology, Genomics, Biotherapy », University of Limoges, France
– Board of the Doctoral School in biological sciences and health ED615 (Confederal university Leonard de Vinci)
– Member of the French society of Immunology, French society of Hematology and International research group on Kidney and Monoclonal Gammopathies (IKMG)
– Member of the national Reference Center for AL amyloidosis and other Monoclonal Ig deposition diseases (head: Pr Arnaud Jaccard, University Hospital of Limoges)

 

Research activities

My research activity is devoted to B cell immunology and immunopathology. More specifically, I am interested in the regulation of immunoglobulin (Ig) expression and production during B cell development. My contribution to the field encompasses allelic exclusion, RNA surveillance, Ig class switch recombination and plasma cell development. Beside this basic research interest, I also contributed to the characterization of genetic alterations of Ig genes and development of mouse models to study the toxicity of abnormal Ig fragments involved in human diseases related to monoclonal Ig deposition including AL amyloidosis, LCDD/HCDD or renal Fanconi syndrome. On behalf of the National reference center for AL amyloidosis and other monoclonal immunoglobulin diseases, I am in charge of the experimental research. I am also involved in translational science with the development of biotechnology tools and innovative therapeutic molecules for the treatment of AL amyloidosis.

 

 

Selected Publications (36 international publications, 4 book chapter and 3 patents)

Bender S, Ayala MV, Bonaud A, Javaugue V, Carrion C, Oblet C… and C.Sirac. Immunoglobulin light chain toxicity in a mouse model of monoclonal immunoglobulin light-chain deposition disease. Blood 2020. doi:10.1182/blood.2020005980.

Ayala MV, Bonaud A, Bender S, Lambert J-M, Lechouane F, Carrion C… and C.Sirac. New models to study plasma cells in mouse based on the restriction of IgJ expression to antibody secreting cells. bioRxiv 2020; : 2020.08.13.249441.

Bender S, Javaugue V, Saintamand A, Ayala MV, Alizadeh M, Filloux M… Sirac C* and A.Jaccard*. Immunoglobulin variable domain high-throughput sequencing reveals specific novel mutational patterns in POEMS syndrome. Blood 2020; 135: 1750–1758.

Bender S, Ayala MV, Javaugue V, Bonaud A, Cogné M, Touchard G … and C.Sirac. Comprehensive molecular characterization of a heavy chain deposition disease case. Haematologica 2018; 103: e557–e560.

Sirac, C., Herrera, G.A., Sanders, P.W., Batuman, V., Bender, S., Ayala, M.V., Javaugue, V., Teng, J., Turbat-Herrera, E.A., Cogné, M., Touchard, G., Leung, N., Bridoux, F., 2018. Animal models of monoclonal immunoglobulin-related renal diseases. Nat Rev Nephrol 14, 246–264.

Bridoux, F., Javaugue, V., Bender, S., Leroy, F., Aucouturier, P., Debiais-Delpech, C., Goujon, J.-M., Quellard, N., Bonaud, A., Clavel, M., Trouillas, P., Di Meo, F., Gombert, J.-M., Fermand, J.-P., Jaccard, A., Cogné, M., Touchard, G., Sirac, C., 2017. Unravelling the immunopathological mechanisms of heavy chain deposition disease with implications for clinical management. Kidney Int. 91, 423–434.

Srour, N., Chemin, G., Tinguely, A., Ashi, M.O., Oruc, Z., Péron, S., Sirac, C., Cogné, M., Delpy, L., 2016. A plasma cell differentiation quality control ablates B cell clones with biallelic Ig rearrangements and truncated Ig production. J. Exp. Med. 213, 109–122.

Luciani, A.*, Sirac, C.*, Terryn, S., Javaugue, V., Prange, J.A., Bender, S., Bonaud, A., Cogné, M., Aucouturier, P., Ronco, P., Bridoux, F., Devuyst, O., 2016. Impaired Lysosomal Function Underlies Monoclonal Light Chain-Associated Renal Fanconi Syndrome. J. Am. Soc. Nephrol. 27, 2049–2061.

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., 2015a. A mouse model recapitulating human monoclonal heavy chain deposition disease evidences the relevance of proteasome inhibitor therapy. Blood 126, 757–765.

Bonaud, A., Lechouane, F., Le Noir, S., Monestier, O., Cogné, M., Sirac, C., 2015b. Efficient AID targeting of switch regions is not sufficient for optimal class switch recombination. Nat Commun 6, 7613.

Sirac, C., Bridoux, F., 2014. Mesangial cells as amyloid factory: a unique contribution of animal models. Kidney Int. 86, 669–671.

Lechouane, F., Bonaud, A., Delpy, L., Casola, S., Oruc, Z., Chemin, G., Cogné, M., Sirac, C., 2013. B-cell receptor signal strength influences terminal differentiation. Eur. J. Immunol. 43, 619–628.

Sirac, C., Bridoux, F., Essig, M., Devuyst, O., Touchard, G., Cogné, M., 2011. Toward understanding renal Fanconi syndrome: step by step advances through experimental models. Contrib Nephrol 169, 247–261.

Sirac, C., Bridoux, F., Carrion, C., Devuyst, O., Fernandez, B., Goujon, J.-M., El Hamel, C., Aldigier, J.-C., Touchard, G., Cogné, M., 2006. Role of the monoclonal kappa chain V domain and reversibility of renal damage in a transgenic model of acquired Fanconi syndrome. Blood 108, 536–543.

Sirac, C., Carrion, C., Duchez, S., Comte, I., Cogné, M., 2006. Light chain inclusion permits terminal B cell differentiation and does not necessarily result in autoreactivity. Proc. Natl. Acad. Sci. U.S.A. 103, 7747–7752.

Delpy, L.*, Sirac, C.*, Magnoux, E., Duchez, S., Cogné, M., 2004b. 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. 101, 7375–7380.
* Contributed Equally