Our lab is interested to prevent renal failure due to hereditary diseases and acute kidney damage. Several genetic conditions are associated with a dysfunction of the cilium (hence the term “ciliopathy”). To understand the function of cilia-associated proteins, we use the multi-ciliated cells of the Xenopus epidermis as a model system to study the function of “ciliopathy” genes. Acute kidney injury (AKI) remains a frequent complication of severe disease. Despite progress in supportive care, the overall mortality and long-term consequences of this complication have not changed significantly. Using laser-induced zebrafish kidney injury, high-resolution video-microscopy, single-cell isolation and transcriptional profiling, genetic manipulation of repair genes, and kidney-specific gene knockout in mouse models, we can now analyze early up-stream signaling events and delineate the down-stream metabolic switches occurring in response to kidney injury. Analyzing the developmental programs and signaling events that are defective in hereditary disease, or triggered in response to injury, we hope to find new approaches to accelerate regeneration and prevent kidney failure.

Ciliopathies, Acute kidney injury, Renal development, Multi-ciliated cells of the Xenopus epidermis, Zebrafish pronephros

10 selected publications

• 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, and Walz G (2018).
  Nat Commun 9, 3660.
• Cilia‐localized LKB1 regulates chemokine signaling, macrophage recruitment, and tissue homeostasis in the kidney.
  Viau A, Bienaimé F, Luka K, Todkar AP, Knoll M, Yakulov TA, Hofherr A, Kretz O, Helmstaedter M, Reichardt W, Braeg S, Aschman T, Merkle A, Pfeifer D, Dumit VI, Gubler M-C, Nitschke R, Huber TB, Terzi F, Dengjel J, Grahammer F, Köttgen M, Busch H, Boerries M, Walz G, Triantafyllopoulou A, and Kuehn EW (2018).
  EMBO J doi: 10.15252/embj.201798615.
• Direct reprogramming of fibroblasts into renal tubular epithelial cells by defined transcription factors.
  Kaminski MM, Tosic J, Kresbach C, Engel H, Klockenbusch J, Müller AL, Pichler R, Grahammer F, Kretz O, Huber TB, Walz G, Arnold SJ, Lienkamp SS (2016).
  Nat Cell Biol. 18, 1269-1280.
• mTORC2 critically regulates renal potassium handling.
  Grahammer F, Nesterov V, Ahmed A, Steinhardt F, Sandner L, Arnold F, Cordts T, Negrea S, Bertog M, Ruegg MA, Hall MN, Walz G, Korbmacher C, Artunc F, Huber TB (2016).
  J Clin Invest 126, 1773-1782.
• The polarity protein Inturned links NPHP4 to Daam1 to control the subapical actin network in multiciliated cells.
  Yasunaga T, Hoff S, Schell C, Helmstädter M, Kretz O, Kuechlin S, Yakulov TA, Engel C, Müller B, Bensch R, Ronneberger O, Huber TB, Lienkamp SS, Walz G (2015).
  J Cell Biol. 211, 963-73.
• Anks3 interacts with nephronophthisis proteins and is required for normal renal development.
  Yakulov TA, Yasunaga T, Ramachandran H, Engel C, Muller B, Hoff S, Dengjel J, Lienkamp SS, Walz G (2015).
  Kidney Int 87, 1191-1200.
• TSC1 activates TGF-beta-Smad2/3 signaling in growth arrest and epithelial-to-mesenchymal transition.
  Thien A, Prentzell MT, Holzwarth B, Klasener K, Kuper I, Boehlke C, Sonntag AG, Ruf S, Maerz L, Nitschke R, Grellscheid SN, Reth M, Walz G, Baumeister R, Neumann-Haefelin E, Thedieck K (2015).
  Dev Cell 32, 617-630.
• Autosomal dominant polycystic kidney disease: the changing face of clinical management.
  Ong AC, Devuyst O, Knebelmann B, Walz G (2015).
  Lancet 385, 1993-2002.
• ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3.
  Hoff S, Halbritter J, Epting D, Frank V, Nguyen TM, van Reeuwijk J, Boehlke C, Schell C, Yasunaga T, Helmstadter M, Mergen M, Filhol E, Boldt K, Horn N, Ueffing M, Otto EA, Eisenberger T, Elting MW, van Wijk JA, Bockenhauer D, Sebire NJ, Rittig S, Vyberg M, Ring T, Pohl M, Pape L, Neuhaus TJ, Elshakhs NA, Koon SJ, Harris PC, Grahammer F, Huber TB, Kuehn EW, Kramer-Zucker A, Bolz HJ, Roepman R, Saunier S, Walz G, Hildebrandt F, Bergmann C, Lienkamp SS (2013).
  Nat Genet 45, 951-956.
• Vertebrate kidney tubules elongate using a planar cell polarity-dependent, rosette-based mechanism of convergent extension.
  Lienkamp SS, Liu K, Karner CM, Carroll TJ, Ronneberger O, Wallingford JB, Walz G (2012).
  Nat Genet 44, 1382-1387.