Molecular bases of rare and inherited kidney diseases: From insult to repair
Team 1 - Remodelling and repair of renal tissue Lab, Inserm UMRS 702
During the past five years, our research projects were focused on the pathomechanisms of membranous nephropathy (MN), a rare (auto-) immune disease affecting the podocyte, to which our team (H.Debiec) has made major contributions, and of a novel systemic disease caused by mutations in the alpha1 chain of type IV collagen (COL4A1), that we called HANAC (Hereditary Angiopathy with Nephropathy, Aneurysms and Cramps), (Emmanuelle.Plaisier). We have identified the first food antigen, cationic bovine serum albumin (cBSA), implicated in immune glomerulopathies and two series of high-risk alleles of the immune response gene HLA-DQA1 and the PLA2R1 gene encoding the receptor for phospholipase A2 involved in MN.
In addition, we have pursued our line of study on the role of matrix metalloproteases (MMP) in renal diseases with a special attention to inherited diseases. We have identified new roles of MMP9 in nephron formation, in cystogenesis, and as an anti-apoptotic factor via the release of SCF (Brigitte Lelongt), and we have further characterized the effects of its splice variant MMP9-DEx2 (R.Piedagnel). Part of the studies on matrix remodelling, particularly those on mediators of fibrosis, has been performed in close collaboration with Team 2 (J.J. Boffa).
We will develop/use new technological approaches such as HLA peptidomics and next generation sequencing techniques: i) to unravel the pathogenic epitopes triggering immune response and the genetics of MN by sequencing HLA-D and PLA2R1 loci and potentially predisposing genes, ii) to identify new gene mutations in HANAC-related disorders and to understand the pathomechanisms of vascular, renal and muscular involvement in knockin mice, as well as the contribution of abnormal basement membrane to cystogenesis, iii) to characterize modifying genes that can reverse a cystic phenotype in revertant PKD mice that we have generated. We will further investigate the role of MMP9 and its splice variant in the cystogenetic process, and participate in a transversal programme aimed at deciphering epigenetic regulation events, particularly the role of histone acetylation in kidney disease progression and repair. Our ultimate goal is to identify druggable molecular targets and to set up new diagnostic assays.
Fields of interest
Contact infoAddress: UMRS 1155, Hôpital Tenon, Bâtiment Recherche,4 rue de la chine
Postal code: 75970
Telephone: + 33 1 56 01 65 08
Fax: + 33 1 56 01 65 12
- Debiec H, Valayannopoulos V, Boyer O, Nöel LH, Callard P, Sarda H, de Lonlay P, Niaudet P, Ronco P
Allo-Immune Membranous Nephropathy and Recombinant Aryl Sulfatase Replacement Therapy: A Need for Tolerance Induction Therapy
J Am Soc Nephrol. 2013 Nov 21.
- Duquesne A, Werbrouck A, Fabiani B, Denoyer A, Cervera P, Verpont MC, Bender S, Piedagnel R, Brocheriou I, Ronco P, Boffa JJ, Aucouturier P, Garderet L
Complete remission of monoclonal gammopathy with ocular and periorbital crystal storing histiocytosis and Fanconi syndrome
Hum Pathol. 44(5), 927-933 (2013)
- Coenen MJ, Hofstra JM, Debiec H, Stanescu HC, Medlar AJ, Stengel B, Boland-Augé A, Groothuismink JM, Bockenhauer D, Powis SH, Mathieson PW, Brenchley PE, Kleta R, Wetzels JF, Ronco P
Phospholipase A2 receptor (PLA2R1) sequence variants in idiopathic membranous nephropathy
J Am Soc Nephrol. 2013 Mar;24(4):677-83.
- Debiec H, Hanoy M, Francois A, Guerrot D, Ferlicot S, Johanet C, Aucouturier P, Godin M, Ronco P
Recurrent membranous nephropathy in an allograft caused by IgG3κ targeting the PLA2 receptor
J Am Soc Nephrol. 23(12), 1949-1954 (2012)
- Kerroch M, Guerrot D, Vandermeersch S, Placier S, Mesnard L, Jouanneau C, Rondeau E, Ronco P, Boffa JJ, Chatziantoniou C, Dussaule JC
Genetic inhibition of Discoidin Domain Receptor 1 protects mice against crescentic glomerulonephritis
Faseb J 26, 4079-4091 (2012)
- Debiec H, Lefeu F, Kemper M, Niaudet P, Deschênes G, Remuzzi G, Ulinski T, Ronco P
Early childhood membranous nephropathy due to cationic bovine serum albumin
N Engl J Med. 2011 Jun 2; 364(22):2101-10.
- Debiec H, Ronco P
PLA2R autoantibodies and PLA2R glomerular deposits in membranous nephropathy
N Engl J Med. 2011 Feb 17;364(7):689-90.
- Stanescu HC, Arcos-Burgos M, Medlar A, Bockenhauer D, Kottgen A, Dragomirescu L, Voinescu C, Patel N, Pearce K, Hubank M, Stephens HA, Laundy V, Padmanabhan S, Zawadzka A, Hofstra JM, Coenen MJ, den Heijer M, Kiemeney LA, Bacq-Daian D et al.
Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy
N Engl J Med. 2011 Feb 17; 364(7):616-26.
- Ronco P, Debiec H
Antigen identification in membranous nephropathy moves toward targeted monitoring and new therapy
J Am Soc Nephrol 2010 Apr;21(4):564-9.
- Plaisier E, Gribouval O, Alamovitch S, Mougenot B, Prost C, Verpont MC, Marro B, Desmettre T, Cohen SY, Roullet E, Dracon M, Fardeau M, Van Agtmael T, Kerjaschki D, Antignac C, Ronco P
Role of COL4A1 mutations in the Hereditary Angiopathy with Nephropathy, Aneurysm and muscle Cramps (HANAC) syndrome
N Engl J Med 2007, 357:2687-95.
- Jaccard A, Moreau P, Leblond V, Leleu X, Benboubker L, Hermine O, Recher C, Asli B, Lioure B, Royer B, Jardin F, Bridoux F, Grosbois B, Jaubert J, Piette JC, Ronco P, Quet F, Cogne M, Fermand JP
High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis
N Engl J Med. 2007 Sep 13;357(11):1083-93.
- Debiec H, Nauta J, Coulet F, van der Burg M, Guigonis V, Schurmans T, de Heer E, Soubrier F, Janssen F, Ronco P
Role of truncating mutations in MME gene in fetomaternal alloimmunisation and antenatal glomerulopathies
Lancet. 2004 Oct 2-8;364(9441):1252-9.
- Debiec H, Guigonis V, Mougenot B, Decobert F, Haymann JP, Bensman A, Deschênes G, Ronco P
Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies
N Engl J Med. 2002 Jun 27;346(26):2053-60.