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Renal Physiology and tubulopathies

Our multidisciplinary team seeks to investigate the mechanisms by which the kidney regulates ionic transport, adapts the body to its environment, and the mechanisms of related disorders.  The kidney matches urinary excretion to the daily intake of water and nutrients. Homeostatic perturbations may occur due to kidney dysfunctions (tubulopathies) or be secondary to systemic disorders (metabolic syndrome, diabetes …) or to the side effects of drugs. They are responsible for a number of renal and extrarenal sequelæ (stone disease and/or nephrocalcinosis, hypertension and cardio-vascular events, life-threatening plasma ionic disorders). Taking advantage of our unique expertise, our project focuses on the renal mechanisms that maintain ion homeostasis, more particularly that of Na and Cl- ions (Aim 1), K ions (Aim 2), divalent cations (Ca2 and Mg2 , Aim 3), on related human disorders (Aim 4) and on the development of technologies needed to investigate these processes (Aim 5).
Modern physiology requires specific, advanced tools and a multidisciplinary approach, both of which constitute our strength. Our studies span multiple scales, from molecules to the entire organism, and rely on a combination of experimental and modeling tools. For many years now, our team has developed a unique platform for the analysis of renal tubular functions and ion transport systems in rodents, which is employed in most of our studies and is accessible to external investigator. We developed techniques to perform segmental analysis of mRNA or protein expression, measurements of ion fluxes, transepithelial currents or intracellular Ca2 or pH modifications in isolated microdissected tubules, and to investigate metabolic and physiologic parameters in order to calculate balances. Now, we seek to maintain and expand this core structure by developing novel technical approaches:1) the purification of exosomes of renal origin from mouse and rat urine and subsequent transcriptomic analysis. 2) the monitoring of water in live animals by nuclear magnetic resonance. This non-invasive approach will bring new insight in the regulation of water homeostasis. 3) the use of the RNASCOPE, a technic to label RNA in fixed tissue at the cellular level allowing us to localize the expression of genes in the kidney for which no antibodies are available.

For more information regarding our lab, you can visit our Facebook page: https://www.facebook.com/Transport.Ionique.Renal/


Team Leader: Gilles CRAMBERT (CR; CNRS)

Members of the team:

Researchers: François ALHENS-GELAS (DR em; Inserm), Lise BANKIR (DR em;  INSERM), Stéphanie BARON (MCU-PH; Univ Paris Descartes), Anne BLANCHARD (MCU-PH; Univ Paris Descartes), Nadine BOUBY (DR; INSERM), DOUCET Alain (DR em; CNRS), Pascal HOUILLIER (PU-PH Univ Paris Descartes), Kamel LAGHMANI (CR; CNRS), Stéphane LOURDEL (MCU Sorbonne Univ), Marc PAULAIS (CR; INSERM), Gabrielle PLANELLES (DR; INSERM), Jacques TEULON (PU em; Sorbonne Univ), Rosa VARGAS-POUSSOU (PHU AP-HP).

Technical staff: Gaëlle BRIDEAU (IR; CNRS), Lydie CHEVAL (IR; CNRS), Sylvie DEMARETZ (IE; Sorbonne Univ), Clément DOUCET (Adj Tec; CDD), Nadia FRACHON (AI; Inserm), Camille GRIVEAU (AI; CDD), Christine LAMOUROUX (IE; CNRS), Luciana MORLA (IE; CNRS). 

Young Researchers: Alal BAKHOS AL DOUAIHY (post-Doc), Caroline BERTOYE  (PhD student), Mona MAHZAR (PhD student), Chloé RAFAEL (Post-Doc), Imène SAHKI (PhD student), Keith SIEW (Post-Doc).

Administration: Dalila HAKER (Tec; CNRS)

 
Publications

  • Scudieri P, Musante I, Caci E, Venturini A, Morelli P, Walter C, Tosi D, Palleschi A, Martin-Vasallo P, Sermet-Gaudelus I, Planelles G, Crambert G, Galietta LJ. Increased expression of ATP12A proton pump in cystic fibrosis airways. JCI Insight. 2018, 18; e1236163
  • Hadj-Rabia S*, Brideau G*, Al-Sarraj Y*, Maroun RC*, Figueres ML, Leclerc-Mercier S, Olinger E, Baron S, Chaussain C,  Nochy D, Taha RZ, Knebelmann B, Joshi V, Curmi PA, Kambouris M, Vargas-Poussou R, Bodemer C, Devuyst O, Houillier P*, El-Shanti H*. Multiplex epithelium dysfunction due to CLAUDIN-10 mutation: the HELIX syndrome. To appear in Genetics in Medicine, 2017 : IF 7.7
  • Laghmani K, Beck BB, Yang S-S, Seaayfan E, Wenzel A, Reusch B, Vitzthum H, Priem D, Demaretz S, Bergmann K, Duin LK, Gobel H, Mache C, Thiele H, Bartram MP, Dombret C, Altmuller J, Nurnberg P, Benzing T, Levtchenko E, Seyberth HW, Klaus G, Yigit G, Lin S-H, Timmer A, de Koning TJ, Scherjon SA, Schlingmann KP, Bertrand MJM, Rinschen MM, de Backer O, Konrad M, and Komhoff M. Polyhydramnios, Transient Antenatal Bartter’s Syndrome, and MAGED2 Mutations. The New England Journal of Medicine 2016; 374: 1853-1863. IF 59.6
  • Mansour-Hendili L, Blanchard A, Pottier NL, Roncelin I, Lourdel S, Treard C, Gonzalez W, Vergara-Jaque A, Morin G, Colin E, Holder-Espinasse M, Bacchetta J, Baudouin V, Benoit S, Berard E, Bourdat-Michel G, Bouchireb K, Burtey S, Cailliez M, Cardon G, Cartery C, Champion G, Chauveau D, Cochat P, Dahan K, la Faille R, Debray FG, Dehoux L, Deschenes G, Desport E, Devuyst O, Dieguez S, Emma F, Fischbach M, Fouque D, Fourcade J, Francois H, Gilbert-Dussardier B, Hannedouche  T, Houillier P, Izzedine H, Janner M, Karras A, Knebelmann B, Lavocat MP, Lemoine S, Leroy V, Loirat C, Macher MA, Martin-Coignard D, Morin D, Niaudet P, Nivet H,  Nobili F, Novo R, Faivre L, Rigothier C, Roussey-Kesler G, Salomon R, Schleich A, Sellier-Leclerc AL, Soulami K, Tiple A, Ulinski T, Vanhille P, Van Regemorter N,  Jeunemaitre X, Vargas-Poussou R. Mutation Update of the Clcn5 Gene Responsible for Dent Disease 1. Hum Mutat 2015; 36: 743-752. IF 5.1
  • Morla L, Doucet A, Lamouroux C, Crambert G*, Edwards A*. The renal cortical collecting duct: a secreting epithelium? J Physiol 2016; 594: 5991-6008. IF 4.7
     

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 Picture 1: Isolation of renal tubular segments

 

Picture 2: Isolated collecting duct (OMCD) under binocular

 

Picture 3: Intercalated cells (red) on isolated tubules

 

Picture 4: Measurement of intracellular pH and Na in parallel on xenopus oocytes

 

Picture 5: Complexity of the ion transport system in the collecting ducts

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