Prof. Dr. Thomas Benzing & Prof. Dr. Bernhard Schermer

Research Area: Ageing-associated Kidney Disease / Nephrology


1. Research Background:

Chronic kidney disease (CKD) is affecting a steadily increasing proportion of the aging population in the industrial world with more than 10% of the population suffering from CKD. Recent evidence indicates that CKD does not only result in end-stage renal failure ultimately requiring dialysis or kidney transplantation: CKD has been identified as a major cardiovascular risk factor and is among the most important non-neoplastic disorders that affect overall survival.

The causes of CKD and age-related renal pathologies are poorly understood but genetic as well as environmental factors clearly play a role. Our lab studies the molecular principles underlying kidney disorders with a strong focus on age-related renal pathologies. Here, we are focusing on glomerular and on degenerative cystic diseases.

2. Research questions addresses by the group:

Three examples from the broad spectrum of our lab:

  1. Over the past several years, we and others have shown that primary cilia and ciliary signaling are required for maintaining kidney architecture and function. Mutations in genes encoding for proteins localized to renal primary cilia are a major cause of polycystic kidney diseases and a variety of degenerative renal disorders in humans, summarized under the term ‘ciliopathies’. Recently, we developed a new mouse model for a very common renal ciliopathy[1] and we used proximity labeling to identify novel ciliary components [2]. Interestingly, kidney degeneration in ciliopathies shares common features with chronic kidney disease in renal aging.
  2. Moreover, recent studies revealed the pivotal role of the hippo signaling effectors YAP/TAZ in maintaining glomerular integrity and preventing the death of specialized cells at the kidney filter called podocytes. We could demonstrate that mechanosensory stimuli control YAP/TAZ activity in podocytes [3]. Now we aim to unravel the mechanisms how YAP/TAZ alterations contribute to podocyte survival and influence renal aging.
  3. Very recently, we used CRISPR/Cas9 to generate knock-in mouse models mimicking late-onset human glomerular disease. With superresolution imaging (STED) and mathematical modeling we suggested a novel model for the understanding of the filtration barrier in the kidney [4].

3. Possible projects:

Possible projects include, but are not limited to the following topics:

  • Premature aging in ciliopathy models and mice lacking cilia (including the model from [1])
  • Dynamic changes of the ciliary proteome during ciliary resorption and signaling and in kidney disease (based on proximity labeling [2])
  • The role of Hippo/YAP/TAZ Signaling in the pathogenesis of FSGS and of age-related glomerular disease (based on models from [3] and [4])
  • Genetic, dietary and pharmacologic interventions to prevent acute kidney injury and renal fibrosis [5]

4. Applied Methods and model organisms:

  • Models and model organisms: 
    M. musculus, C. elegans, human and murine cell lines, primary cells, stem cells, 3D organoids, human biopsy material
  • Methods (selection):
    2D/3D cell culture; genome editing primarily based on CRISPR/Cas9 in mice, cultured human cells and worms; lenti-/retroviral gene transfer; molecular cloning; FACS; genomics (RNAseq, ChIPseq, Nanopore …); RBP analysis; proteomics; confocal imaging; super resolution microscopy (STED/GSD); 2P-in-vivo-imaging of the kidney [6]; hybridoma techniques; lncRNA analysis; etc.

5. Desirable skills and qualifications:

We are searching for highly motivated young scientists with great enthusiasm for biomedical research and with qualities of great team-players.

6. References:

Please find a full list of our publications on our webpage. Here you will also find an overview of our projects and our contact information in case of any questions.

  1. Jain, M., Kaiser, R.W.J., Bohl, K., Hoehne, M., Gobel, H., Bartram, M.P., Habbig, S., Muller, R.U., Fogo, A.B., Benzing, T., Schermer, B., Hopker, K., and Slaats, G.G. (2019). Inactivation of Apoptosis Antagonizing Transcription Factor in tubular epithelial cells induces accumulation of DNA damage and nephronophthisis. Kidney Int 95, 846-858.
  2. Kohli, P., Hohne, M., Jungst, C., Bertsch, S., Ebert, L.K., Schauss, A.C., Benzing, T., Rinschen, M.M., and Schermer, B. (2017). The ciliary membrane-associated proteome reveals actin-binding proteins as key components of cilia. EMBO Rep 18, 1521-1535.
  3. 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.
  4. Butt, L., Unnersjö-Jess, D., Höhne, M., Edwards, A., Binz-Lotter, J., Reilly, D., Hahnfeldt, R., Ziegler, V., Fremter, K., Rinschen, M.M., Helmstädter, 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. Nature Metabolism.
  5. Johnsen, M., Kubacki, T., Yeroslaviz, A., Spath, M.R., Morsdorf, J., Gobel, H., Bohl, K., Ignarski, M., Meharg, C., Habermann, B., Altmuller, J., Beyer, A., Benzing, T., Schermer, B., Burst, V., and Muller, R.U. (2020). The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury. J Am Soc Nephrol 31, 716-730.
  6. Binz-Lotter, J., Jungst, C., Rinschen, M.M., Koehler, S., Zentis, P., Schauss, A., Schermer, B., Benzing, T., and Hackl, M.J. (2020). Injured Podocytes Are Sensitized to Angiotensin II-Induced Calcium Signaling. J Am Soc Nephrol 31, 532-542.