faculty members
Veronique Fremeaux-Bacchi
MD PhD
INSERM UMRS1138, Centre de Recherche des Cordeliers, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, France
Veronique Fremeaux-Bacchi aims to understand the roles of complement regulation in health and disease

We aim to translate our knowledge acquired through fundamental research into the clinical practice through development of novel diagnostic tests and the use of recent high-throughput genomic technologies including next generation sequencing and by innovative drug design strategies.

A major research interest of our group is to understand the implication of complement in human pathologies, with a particular accent on the link between complement dysregulation and overactivation with the development of kidney diseases. The major achievements related to kidney diseases are: the first discovery of Factor I (J. Med. Genet), C3 (Blood) and DGKe (Nature Genetics) genetic abnormalities as well as anti-Factor H antibodies (JASN) in aHUS; the clinical description of one of the largest C3 Glomerulopathy cohort and the first description of a pathogenic antibody, stabilizing the C5 convertase C5NeF (Kidney Int). We reported the largest cohort worldwide of genetic abnormalities identify in patients with complement deficiency (Frontiers of immunology). The clinical and basic research activities resulted in more than 100 papers published within the last 10 years. Presently, my group are studying 1) auto-antibodies directed against complement proteins in C3 Glomerulopathy. We aim to Identified the mechanisms leading to generation of auto-antibodies against complement proteins in C3G as well as characterization of their functional consequences and disease relevance.  2) the mechanisms of C3G, related to monoclonal gammopathies (a pre-cancerous condition) of renal significance. In an available cohort, we will characterize the physicochemical and binding properties, which make monoclonal immunoglobulins complement-activating entities and how this induces renal damage.3) the genetic susceptibility for the severe meningococcal infections and screening diagnostic tools for following complement activation during the disease. Our work will lead to novel strategies for treatment of severe meningococcal infections and may open new avenues for fighting infections caused by multidrug-resistant neisserial or streptococcal strains.

selected
publications

Chauvet S, Roumenina LT, Bruneau S, Marinozzi MC, Rybkine T, Schramm EC, Java A, Atkinson JP, Aldigier JC, Bridoux F, Touchard G, Fremeaux-Bacchi V. A Familial C3GN Secondary to Defective C3 Regulation by Complement Receptor 1 and Complement Factor H. J Am Soc Nephrol 27(6):1665-1677 (2016).

El Karoui K, Boudhabhay I, Petitprez F, Vieira-Martins P, Fakhouri F, Zuber J, Aulagnon F, Matignon M, Rondeau E, Mesnard L, Halimi JM, Frémeaux-Bacchi V. Impact of hypertensive emergency and complement rare variants on presentation and outcome of atypical hemolytic uremic syndrome. Haematologica pii: haematol.2019.216903 (Epub ahead of print, 2019).

El Sissy C, Rosain J, Vieira-Martins P, Bordereau P, Gruber A, Devriese M, de Pontual L, Taha MK, Fieschi C, Picard C, Frémeaux-Bacchi V. Clinical and Genetic Spectrum of a Large Cohort With Total and Sub-total Complement Deficiencies. Front Immunol 10:1936 (2019).

Veronique Fremeaux-Bacchi
MD PhD
INSERM UMRS1138, Centre de Recherche des Cordeliers, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, France

Veronique Fremeaux-Bacchi aims to understand the roles of complement regulation in health and disease

We aim to translate our knowledge acquired through fundamental research into the clinical practice through development of novel diagnostic tests and the use of recent high-throughput genomic technologies including next generation sequencing and by innovative drug design strategies.

A major research interest of our group is to understand the implication of complement in human pathologies, with a particular accent on the link between complement dysregulation and overactivation with the development of kidney diseases. The major achievements related to kidney diseases are: the first discovery of Factor I (J. Med. Genet), C3 (Blood) and DGKe (Nature Genetics) genetic abnormalities as well as anti-Factor H antibodies (JASN) in aHUS; the clinical description of one of the largest C3 Glomerulopathy cohort and the first description of a pathogenic antibody, stabilizing the C5 convertase C5NeF (Kidney Int). We reported the largest cohort worldwide of genetic abnormalities identify in patients with complement deficiency (Frontiers of immunology). The clinical and basic research activities resulted in more than 100 papers published within the last 10 years. Presently, my group are studying 1) auto-antibodies directed against complement proteins in C3 Glomerulopathy. We aim to Identified the mechanisms leading to generation of auto-antibodies against complement proteins in C3G as well as characterization of their functional consequences and disease relevance.  2) the mechanisms of C3G, related to monoclonal gammopathies (a pre-cancerous condition) of renal significance. In an available cohort, we will characterize the physicochemical and binding properties, which make monoclonal immunoglobulins complement-activating entities and how this induces renal damage.3) the genetic susceptibility for the severe meningococcal infections and screening diagnostic tools for following complement activation during the disease. Our work will lead to novel strategies for treatment of severe meningococcal infections and may open new avenues for fighting infections caused by multidrug-resistant neisserial or streptococcal strains.


selected publications:

Lemaire M*, Fremeaux-Bacchi V* et al. Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome. Nat Genet 45:531-6 (2013). * equal contribution

Fremeaux-Bacchi V et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol 8:554-62 (2013).

Schramm EC, Roumenina LT, Rybkine T, Chauvet S, Vieira-Martins P, Hue C, Maga T, Valoti E, Wilson V, Jokiranta S, Smith RJ, Noris M, Goodship T, Atkinson JP, Fremeaux-Bacchi V. Functional mapping of the interactions between complement C3 and regulatory proteins using atypical hemolytic uremic syndrome-associated mutations. Blood 125(15):2359-69 (2015).

Chauvet S, Roumenina LT, Bruneau S, Marinozzi MC, Rybkine T, Schramm EC, Java A, Atkinson JP, Aldigier JC, Bridoux F, Touchard G, Fremeaux-Bacchi V. A Familial C3GN Secondary to Defective C3 Regulation by Complement Receptor 1 and Complement Factor H. J Am Soc Nephrol 27(6):1665-1677 (2016).

El Karoui K, Boudhabhay I, Petitprez F, Vieira-Martins P, Fakhouri F, Zuber J, Aulagnon F, Matignon M, Rondeau E, Mesnard L, Halimi JM, Frémeaux-Bacchi V. Impact of hypertensive emergency and complement rare variants on presentation and outcome of atypical hemolytic uremic syndrome. Haematologica pii: haematol.2019.216903 (Epub ahead of print, 2019).

El Sissy C, Rosain J, Vieira-Martins P, Bordereau P, Gruber A, Devriese M, de Pontual L, Taha MK, Fieschi C, Picard C, Frémeaux-Bacchi V. Clinical and Genetic Spectrum of a Large Cohort With Total and Sub-total Complement Deficiencies. Front Immunol 10:1936 (2019).


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PROGRAMME SPEAKER

Reinhard Würzner, M.D., Ph.D.
Schöpfstraße 41
A-6020 Innsbruck

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This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 860044