FSGS represents one of the most common hallmarks of podocyte stress and damage. To this date, the underlying mechanisms specifically in primary and recurrent FSGS are poorly understood. Via the analysis of patient samples obtained from very well defined cohorts in combination with novel in vitro and in vivo disease modeling, we aim to uncover conserved molecular pathways altered during the course of Focal Segmental Glomerulosclerosis. Especially we follow the hypothesis that in early stages immunologically triggered alterations of glomerular epithelial cells occur. These immuno-epithelial interactions as a potential therapeutic target are in the focus of our CRC 1192 associated project.

 

Die Fokal Segmentale Glomerulosklerose (FSGS) stellt eine der Hauptursachen für die terminale Niereninsuffizienz dar. Sie ist gekennzeichnet von einer fokalen Sklerose der Glomeruli in vereinzelten renalen Segmenten. Die Mechanismen der primären und rekurrenten FSGS sind bisher noch unzureichend verstanden. Wir gehen davon aus, dass es sich im frühen Stadium um immunologisch vermittelte Veränderungen der glomerulären Epithelzellen handelt und diese ein potenzielles therapeutisches Ziel darstellen. Das SFB assoziierte Projekt widmet sich daher den spezifischen immun-epithelialen Interaktionen in der Pathogenese der primären FSGS.


Researchers:

Fabian Braun

Jan Czogalla

Victor Puelles

Inka Homeyer

Oliver Kretz






Related publications:

  • Genetic and pharmacological inhibition of microRNA-92a maintains podocyte cell cycle quiescence and limits crescentic glomerulonephritis.Henique C, Bollée G, Loyer X, Grahammer F, Dhaun N, Camus M, Vernerey J, Guyonnet L, Gaillard F, Lazareth H, Meyer C, Bensaada I, Legrès L, Satoh T, Akira S, Bruneval P, Dimmeler S, Tedgui A, Karras A, Thervet E, Nochy D, Huber TB, Mesnard L, Lenoir O, Tharaux PL.Nat Commun. 2017 Nov 28;8(1):1829.
  • Mitochondrial Priming by CD28.Klein Geltink RI, O'Sullivan D, Corrado M, Bremser A, Buck MD, Buescher JM, Firat E, Zhu X, Niedermann G, Caputa G, Kelly B, Warthorst U, Rensing-Ehl A, Kyle RL, Vandersarren L, Curtis JD, Patterson AE, Lawless S, Grzes K, Qiu J, Sanin DE, Kretz O, Huber TB, Janssens S, Lambrecht BN, Rambold AS, Pearce EJ, Pearce EL.Cell. 2017 Oct 5;171(2):385-397.e11.
  • Cytoprotective activated protein C averts Nlrp3 inflammasome-induced ischemia-reperfusion injury via mTORC1 inhibition.Nazir S, Gadi I, Al-Dabet MM, Elwakiel A, Kohli S, Ghosh S, Manoharan J, Ranjan S, Bock F, Braun-Dullaeus RC, Esmon CT, Huber TB, Camerer E, Dockendorff C, Griffin JH, Isermann B, Shahzad K.Blood. 2017 Dec 14;130(24):2664-2677.
  • N-Degradomic Analysis Reveals a Proteolytic Network Processing the Podocyte Cytoskeleton.Rinschen MM, Hoppe AK, Grahammer F, Kann M, Völker LA, Schurek EM, Binz J, Höhne M, Demir F, Malisic M, Huber TB, Kurschat C, Kizhakkedathu JN, Schermer B, Huesgen PF, Benzing T.J Am Soc Nephrol. 2017 Oct;28(10):2867-2878.
  • The FERM protein EPB41L5 regulates actomyosin contractility and focal adhesion formation to maintain the kidney filtration barrier.Schell C, Rogg M, Suhm M, Helmstädter M, Sellung D, Yasuda-Yamahara M, Kretz O, Küttner V, Suleiman H, Kollipara L, Zahedi RP, Sickmann A, Eimer S, Shaw AS, Kramer-Zucker A, Hirano-Kobayashi M, Abe T, Aizawa S, Grahammer F, Hartleben B, Dengjel J, Huber TB.Proc Natl Acad Sci U S A. 2017 Jun 6;114(23):E4621-E4630.
  • Targeting mTOR Signaling Can Prevent the Progression of FSGS.Zschiedrich S, Bork T, Liang W, Wanner N, Eulenbruch K, Munder S, Hartleben B, Kretz O, Gerber S, Simons M, Viau A, Burtin M, Wei C, Reiser J, Herbach N, Rastaldi MP, Cohen CD, Tharaux PL, Terzi F, Walz G, Gödel M, Huber TB.J Am Soc Nephrol. 2017 Jul;28(7):2144-2157.
  • NorUrsodeoxycholic acid ameliorates cholemic nephropathy in bile duct ligated mice.Krones E, Eller K, Pollheimer MJ, Racedo S, Kirsch AH, Frauscher B, Wahlström A, Ståhlman M, Trauner M, Grahammer F, Huber TB, Wagner K, Rosenkranz AR, Marschall HU, Fickert P.J Hepatol. 2017 Jul;67(1):110-119.
  • Modeling Monogenic Human Nephrotic Syndrome in the Drosophila Garland Cell Nephrocyte.Hermle T, Braun DA, Helmstädter M, Huber TB, Hildebrandt F.J Am Soc Nephrol. 2017 May;28(5):1521-1533.
  • CXCL12 and MYC control energy metabolism to support adaptive responses after kidney injury.Yakulov TA, Todkar AP, Slanchev K, Wiegel J, Bona A, Groß M, Scholz A, Hess I, Wurditsch A, Grahammer F, Huber TB, Lecaudey V, Bork T, Hochrein J, Boerries M, Leenders J, de Tullio P, Jouret F, Kramer-Zucker A, Walz G.Nat Commun. 2018 Sep 10;9(1):3660.
  • DNA Methyltransferase 1 Controls Nephron Progenitor Cell Renewal and Differentiation.Wanner N, Vornweg J, Combes A, Wilson S, Plappert J, Rafflenbeul G, Puelles VG, Rahman RU, Liwinski T, Lindner S, Grahammer F, Kretz O, Wlodek ME, Romano T, Moritz KM, Boerries M, Busch H, Bonn S, Little MH, Bechtel-Walz W, Huber TB.J Am Soc Nephrol. 2019 Jan;30(1):63-78.
  • ARP3 Controls the Podocyte Architecture at the Kidney Filtration Barrier.Schell C, Sabass B, Helmstaedter M, Geist F, Abed A, Yasuda-Yamahara M, Sigle A, Maier JI, Grahammer F, Siegerist F, Artelt N, Endlich N, Kerjaschki D, Arnold HH, Dengjel J, Rogg M, Huber TB.Dev Cell. 2018 Dec 17;47(6):741-757.e8.
  • Development and validation of a renal risk score in ANCA-associated glomerulonephritis.Brix SR, Noriega M, Tennstedt P, Vettorazzi E, Busch M, Nitschke M, Jabs WJ, Özcan F, Wendt R, Hausberg M, Sellin L, Panzer U, Huber TB, Waldherr R, Hopfer H, Stahl RAK, Wiech T.Kidney Int. 2018 Dec;94(6):1177-1188.
  • Cilia-localized LKB1 regulates chemokine signaling, macrophage recruitment, and tissue homeostasis in the kidney.Viau A, Bienaimé F, Lukas K, Todkar AP, Knoll M, Yakulov TA, Hofherr A, Kretz O, Helmstädter M, Reichardt W, Braeg S, Aschman T, Merkle A, Pfeifer D, Dumit VI, Gubler MC, Nitschke R, Huber TB, Terzi F, Dengjel J, Grahammer F, Köttgen M, Busch H, Boerries M, Walz G, Triantafyllopoulou A, Kuehn EW.EMBO J. 2018 Aug 1;37(15). pii: e98615.
  • A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes.Rinschen MM, Gödel M, Grahammer F, Zschiedrich S, Helmstädter M, Kretz O, Zarei M, Braun DA, Dittrich S, Pahmeyer C, Schroder P, Teetzen C, Gee H, Daouk G, Pohl M, Kuhn E, Schermer B, Küttner V, Boerries M, Busch H, Schiffer M, Bergmann C, Krüger M, Hildebrandt F, Dengjel J, Benzing T, Huber TB.Cell Rep. 2018 May 22;23(8):2495-2508.
  • Single-nephron proteomes connect morphology and function in proteinuric kidney disease. Höhne M, Frese CK, Grahammer F, Dafinger C, Ciarimboli G, Butt L, Binz J, Hackl MJ, Rahmatollahi M, Kann M, Schneider S, Altintas MM, Schermer B, Reinheckel T, Göbel H, Reiser J, Huber TB, Kramann R, Seeger-Nukpezah T, Liebau MC, Beck BB, Benzing T, Beyer A, Rinschen MM.Kidney Int. 2018 Jun;93(6):1308-1319.
  • The cell fate determinant Scribble is required for maintenance of hematopoietic stem cell function.Kähne T, Bullinger L, Heidel FH. Weinert S, Godavarthy S, Zanetti C, Naumann M, Hartleben B, Huber TB, Krause DS, Mohr J, Dash BP, Schnoeder TM, Wolleschak D, Herzog C, Tubio Leukemia. 2018 May;32(5):1211-1221.
  • FERMT2 links cortical actin structures, plasma membrane tension and focal adhesion function to stabilize podocyte morphology. Yasuda-Yamahara M, Rogg M, Frimmel J, Trachte P, Helmstaedter M, Schroder P, Schiffer M, Schell C, Huber TB.Matrix Biol. 2018 Aug;68-69:263-279.