Renal physiology and tubulopathies
Directeur : 
Gilles Crambert
Directeur adjoint : 
Pascal Houillier
Nous étudions les mécanismes par lesquels le rein régule le transport ionique et les mécanismes des pathologies associés (tubulopathies). Nous réalisons des analyses segmentaires de l’expression de l’ARNm/des protéines, des mesures de flux ioniques, des courants transépithéliaux ou des modifications du Ca2+/pH intracellulaire dans des tubules isolés microdisséqués, une technologie pour laquelle nous disposons d’une expertise unique. Nous étudions également les paramètres métaboliques et physiologiques chez les rongeurs.
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Thèmes scientifiques
Homéostasie du sel et ses troubles
Nous étudions certains aspects de la régulation des transporteurs de Na+ ou de Cl- et leurs effets sur l'homéostasie globale du NaCl à l'état normal ou dans des pathologies (syndromes de Bartter et de Gitelman).
Homéostasie du potassium et ses troubles
Nous étudions certains aspects de la régulation de l'homéostasie du K+ à l'état normal ou dans des pathologies (maladie rénale chronique, COVID19).
Homéostasie des cations divalents et ses troubles
Nous étudions divers aspects de la régulation de l'homéostasie du Ca2+ et du Mg2+ dans des états normaux et pathologiques (maladie de Dent, hypercalciurie, hypercalcémie, néphrocalcinose ou lithiase).
Recherche génétique et translationnelle sur les tubulopathies
Phénotypage des tubulopathies héréditaires - relations phénotype/génotype - essais cliniques et thérapeutiques
Centre d'investigation de la fonction rénale
Notre équipe a développé une plateforme unique pour l'analyse des fonctions tubulaires rénales et des systèmes de transport d'ions chez les rongeurs, qui est utilisée dans la plupart de nos études et est accessible aux chercheurs externes.
Principales publications
The apical 70-pS potassium K channel in the thick ascending limb of Henle’s loop is a large-conductance Na+-and Cl–activated, KNa1.1-like, channel. de Combiens E, Frachon N, Cheval L, Lourdel S, Paulais M. Am J Physiol Renal Physiol. (2024) link
Editorial: New advances in the renal regulation of K+ homeostasis in health and disease. Crambert G, Al-Qusairi L. Front Physiol. 2023 link
Renal K+ retention in physiological circumstances: focus on adaptation of the distal nephron and cross-talk with Na+ transport systems. Lasaad S, Crambert G. Front Physiol. 2023 Link
GDF15 mediates renal cell plasticity in response to potassium depletion in mice. Lasaad S, Walter C, Rafael C, Morla L, Doucet A, Picard N, Blanchard A, Fromes Y, Matot B, Crambert G, Cheval L. Acta Physiol (Oxf). 2023 link
pH-dependence of the Plasmodium falciparum chloroquine resistance transporter is linked to the transport cycle. Berger F, Gomez GM, Sanchez CP, Posch B, Planelles G, Sohraby F, Nunes-Alves A, Lanzer M. Nat Commun. 2023. link
Claudin-19 localizes to the thick ascending limb where its expression is required for junctional claudin-16 localization. Dimke H, Griveau C, Ling WE, Brideau G, Cheval L, Muthan P, Müller D, Al-Shebel A, Houillier P, Prot-Bertoye C. Ann N Y Acad Sci. link
Acidosis-induced activation of distal nephron principal cells triggers Gdf15 secretion and adaptive proliferation of intercalated cells. Cheval L, Viollet B, Klein C, Rafael C, Figueres L, Devevre E, Zadigue G, Azroyan A, Crambert G, Vogt B, Doucet A.Acta Physiol (Oxf). 2021 Jul;232(3):e13661. link
Defective bicarbonate reabsorption in Kir4.2 potassium channel deficient mice impairs acid-base balance and ammonia excretion. Bignon Y, Pinelli L, Frachon N, Lahuna O, Figueres L, Houillier P, Lourdel S, Teulon J, Paulais M. Kidney Int. 2020 Feb;97(2):304-315 link
High-throughput sequencing contributes to the diagnosis of tubulopathies and familial hypercalcemia hypocalciuria in adults. Hureaux M, Ashton E, Dahan K, Houillier P, Blanchard A, Cormier C, Koumakis E, Iancu D, Belge H, Hilbert P, Rotthier A, Del Favero J, Schaefer F, Kleta R, Bockenhauer D, Jeunemaitre X, Devuyst O, Walsh SB, Vargas-Poussou R. Kidney Int. 2019 Dec;96(6):1408-1416. link
Adrenal adaptation in potassium-depeletd men : role of progesterone ? Blanchard A, Brailly Tabard S, Lamaziere A, Bergerot D, Zhygalina V, Lorthioir A, Jacques A, Hourton D, Azizi M, Crambert G. Nephrol Dial Transplant, 2019, gfz135 (ahead of print). IF 4.1 link
Increased expression of ATP12A proton pump in cystic fibrosis airways. P. Scudieri, I. Mussante, E. Caci, A. Venturini, P. Morelli, C.Walter, D. Tosi, A. Palleschi, P. Martin-Vassalo, I. Sermet-Gaudelus, G. Planelles, G. Crambert And L. Galietta. JCI insight (2018), 3, pii 123616. IF 6.0 link
Clinical and Genetic Spectrum of Type 3 Bartter Syndrome. Seys E, Andrini O, Keck M, Mansour-Hendili L, Courand PY, Simian C, Deschenes G, Kwon T, Bertholet A, Bobrie G, Borde JS, Bourdat-Michel G, Brochard K, Cailliez M, Charbit M, Cozette P, Davourie A, Dubourge L, Fila M, Jourde-Chiche N, Lavocat MP, Lemoine S, Lichtenberg L, LLanas B, Louillet F, Merieau E, Mileva M, Mota-Vieiria L, Mousson C, Nobili F, Novo R, Roussey-Kesler G, Vrillon I, Walsh S, Teulon J, Blanchard A, Vargas-Poussou R. J Am Soc Nephrol, 2017 ; 28 :2540-2552 : IF 8.5 link
Polyhydramnios Transient Antenatal Bartter’s Syndrome, and MAGED2 Mutations. 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. The New England Journal of Medicine 2016; 374: 1853-1863. IF 59.6 link
Toutes les publications
Membres de l'équipe
Chercheurs
Enseignants-Chercheurs
Hospitaliers/Hospitalo-universitaires
ITA/ITRF/BIATSS
Offre d'emploi
1 YEAR POST-DOCTORAL POSITION (RENEWABLE 1 YEAR)
Title: Dent Disease – Evolution and treatments
Job offer: A one year post-doctoral position is available (renewable once), under the supervision of Stéphane Lourdel, in the Gilles Crambert team “Renal physiology and tubulopathies”, at the Centre de Recherche des Cordeliers, Paris, France
The host group explores the cellular and the molecular mechanisms involved in Dent disease type 1, a rare inherited disorder of the proximal tubule characterized by low molecular weight proteinuria, hypercalciuria with nephrolithiasis, and progressive renal failure. The disease is caused by inactivating mutations in the CLCN5 gene encoding the 2Cl-/H+ exchanger ClC-5. Until now, there is no specific treatment.
To understand more precisely the cellular and the molecular mechanisms involved in the physiopathology of Dent Disease type 1, we have generated a knock-in (KI) mouse
model stably carrying a ClC-5 mutation that belongs to the most frequent class of mutants observed in patients with Dent disease type 1. Our previous investigations using the KI animals demonstrate that mitochondria may play a crucial role in the pathophysiology of Dent Disease type 1.
We also demonstrated that the transgenic mice displayed progressive renal inflammation and subsequent fibrosis with aging. In addition, we observed that the KI mice did not gain weight and showed significantly less fat mice then control mice. In addition, these animals displayed a progressive attenuation of glucosuria with age. This suggests a possible switch in their general metabolism and handling of metabolites. Moreover, ClC-5 is expressed in other tissues such as the liver where its
function has never been explored previously. As a whole, our project aims at to further investigating the cellular and molecular mechanisms involved in the evolution of Dent disease type 1, and at identifying relevant therapeutic strategies to slow down the progression of this disease. So far, no correlation between genotype and phenotype has been established for patients with Dent disease type 1 as several parameters were not taken into account. Therefore, the postdoc will also aim at
studying clinical parameters in close collaboration with the hospital.
For the development of this project, the selected applicant will use in vivo and in vitro approaches, and will benefit from the strong expertise of the host laboratory in the analysis of the renal phenotype of transgenic mice, and their exploration at the cellular and the molecular levels. An access to state-of-the-art techniques will be provided in the Centre de Recherche des Cordeliers.
Qualifications and experience: Applicants will hold PhD in Physiology and Physiopathology with strong experience in molecular biology, biochemistry and immunohistochemistry. An official approved training for animal experimenting is recommended. Skills in renal pathophysiology would be an asset. The selected candidate should be highly motivated, enthusiastic, independent and team-oriented scientist.
Scientific environment: The laboratory belongs to the “Centre de Recherche des Cordeliers” (www.crcordeliers.fr) located in Paris. In addition to the scientific environment if this institute, the laboratory has access to extensive research core facilities including an animal facility.
Contact: Applicants are invited to send a CV with a list of publications, a summary of research experience, a letter motivation and contact information of referees to stephane.lourdel@sorbonne-universite.fr and elise.de_combiens@etu.sorbonne-universite.fr
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