back to overview

Priv-Doz. Dr. med. Sandra Habbig
Children´s and Adolescents´ Hospital
University Hospital Cologne, Kerpener Str. 62
50937 Cologne, Germany
+49 221 478-4319

Group Leader
Prof. Dr. med. Bernhard Schermer
Department II of Internal Medicine
University Hospital Cologne CECAD Research Center
Joseph-Stelzmann-Str. 26
50931 Cologne, Germany
+49 221 478-89030

University Hospital of Cologne
Nephrolab Cologne
CECAD Research Center
Joseph-Stelzmann-Str. 26
50931 Cologne, Germany

back to overview

Sandra Habbig, Bernhard Schermer

Transcriptional programs governed by YAP and TAZ and their nuclear control mechanisms in FSGS

The transcriptional regulators YAP and TAZ, downstream targets of the Hippo signaling pathway, play a central role in maintaining the homeostasis and survival of podocytes. Consequently, they are indispensable for sustaining glomerular architecture and function. Remarkably, both the hyperactivity of YAP and TAZ, as well as the loss of YAP and TAZ activity, are associated with podocyte damage and glomerular diseases. Precisely controlled regulatory mechanisms are required to maintain a balance in YAP and TAZ activity.

Fundamental studies have revealed that YAP and TAZ operate downstream of various pathways and biological processes, receiving numerous inputs. Despite a vast diversity of tissue- and cell-specific mechanisms and functions that either restrain YAP/TAZ activity or unleash their transcriptional functions, these converge in the nuclear shuttling of YAP and TAZ. This involves their binding to transcription factors, association with enhancer elements, and regulation through posttranslational modifications

Our project aims to uncover how YAP and TAZ activate overlapping and distinct transcriptional programs in podocytes, impacting injury or survival. We'll explore the interchangeable and unique functions of YAP and TAZ in FSGS-related pathways. Examining YAP/TAZ-driven transcription and nucleoporin-controlled shuttling dynamics, we'll unveil their role in podocytes. Additionally, we'll study YAP and TAZ responses to glomerular hemodynamic changes. This research seeks to innovate YAP/TAZ signaling for potential FSGS therapies.


Ester, L., Cabrita, I., Ventzke, M., Kieckhofer, E., Christodoulou, M., Mandel, A.M., Diefenhardt, P., Fabretti, F., Benzing, T., Habbig, S., and Schermer, B. (2023) The role of the FSGS disease gene product and nuclear pore protein NUP205 in regulating nuclear localization and activity of transcriptional regulators YAP and TAZ. Hum Mol Genet. (in press)

Fabretti, F., Tschernoster, N., Erger, F., Hedergott, A., Buescher, A.K., Dafinger, C., Reusch, B., Kontges, V.K., Kohl, S., Bartram, M.P., Weber, L.T., Thiele, H., Altmueller, J., Schermer, B., Beck, B.B., and Habbig, S. (2021) Expanding the Spectrum of FAT1 Nephropathies by Novel Mutations That Affect Hippo Signaling. Kidney Int Rep,  6(5): 1368-1378.

Muller, R.U. and Schermer, B. (2020) Hippo signaling-a central player in cystic kidney disease? Pediatr Nephrol,  35(7): 1143-1152.

Butt, L., Unnersjo-Jess, D., Hohne, M., Edwards, A., Binz-Lotter, J., Reilly, D., Hahnfeldt, R., Ziegler, V., Fremter, K., Rinschen, M.M., Helmstadter, M., Ebert, L.K., Castrop, H., Hackl, M.J., Walz, G., Brinkkoetter, P.T., Liebau, M.C., Tory, K., Hoyer, P.F., Beck, B.B., Brismar, H., Blom, H., Schermer, B., and Benzing, T. (2020) A molecular mechanism explaining albuminuria in kidney disease. Nat Metab,  2(5): 461-474.

Rinschen, M.M., Grahammer, F., Hoppe, A.K., Kohli, P., Hagmann, H., Kretz, O., Bertsch, S., Hohne, M., Gobel, H., Bartram, M.P., Gandhirajan, R.K., Kruger, M., Brinkkoetter, P.T., Huber, T.B., Kann, M., Wickstrom, S.A., Benzing, T., and Schermer, B. (2017) YAP-mediated mechanotransduction determines the podocyte's response to damage. Sci Signal,  10(474).

Kohli, P., Bartram, M.P., Habbig, S., Pahmeyer, C., Lamkemeyer, T., Benzing, T., Schermer, B., and Rinschen, M.M. (2014) Label-free quantitative proteomic analysis of the YAP/TAZ interactome. Am J Physiol Cell Physiol,  306(9): C805-18.

Habbig, S., Bartram, M.P., Sagmuller, J.G., Griessmann, A., Franke, M., Muller, R.U., Schwarz, R., Hoehne, M., Bergmann, C., Tessmer, C., Reinhardt, H.C., Burst, V., Benzing, T., and Schermer, B. (2012) The ciliopathy disease protein NPHP9 promotes nuclear delivery and activation of the oncogenic transcriptional regulator TAZ. Hum Mol Genet,  21(26): 5528-38.

Habbig, S., Bartram, M.P., Muller, R.U., Schwarz, R., Andriopoulos, N., Chen, S., Sagmuller, J.G., Hoehne, M., Burst, V., Liebau, M.C., Reinhardt, H.C., Benzing, T., and Schermer, B. (2011) NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway. J Cell Biol,  193(4): 633-42.