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Linus Völker

Genetical and biochemical profiling of renal disease

Chronic kidney disease is an important risk factor for premature ageing. Damage to podocytes, the visceral epithelial cell of the glomerular filtration unit of the kidney, may lead to proteinuria, nephrotic syndrome with edema, and eventually chronic kidney disease. Minimal Change Disease (MCD) and Focal and Segmental Glomerulosclerosis (FSGS) are part of this group of diseases aptly termed “podocytopathies” that remain poorly understood in terms of pathogenesis and risk factors. Current treatment options include mainly unspecific immunosuppressive regimens with unfavorable side-effects. Recent research has identified alterations in the ubiquitinome, the sum of posttranslational protein modifications by ubiquitin-moieties, as an important factor in podocyte homeostasis. Our group could show that a conditional deletion of the E3-ubiquitin ligase HUWE1 (a.k.a. Mule, ARF-Bp1, HECT9 among others) from the podocyte genome was associated with glomerular sclerosis, loss of kidney function, and premature death in a mouse model. HUWE1 acts as a highly versatile E3-ubiquitin ligase generating various ubiquitin chain-types and modifies the podocyte’s ubiquitinome globally. We have designed a bioinformatic multiomics approach to comprehensively analyze the HUWE1-dependent effects on translational, transcriptional, and post-translational level. Future research is intended to apply this approach to other genetic or pharmacological mouse models of podocytopathies to generate an intertwined map of cross-level changes in the podocyte.

To translate these findings into human disease, our group draws from the resources of the Cologne-based patient registry of glomerular disease, FOrMe ( We have developed a mass-spectrometric workflow to extract proteomics data from patients’ kidney biopsy samples via laser capture microdissection, which we aim to expand to other levels of the multiomics approach. The workflow will be refined by designing targeted proteomics assays that enable a consistent, precise, and sensitive measurement of glomerular signaling activity in health and disease-states from patient biomaterial.

Ongoing projects investigate the specific effects of ubiquitin linkage-types in podocytes and ubiquitin-dependent regulation of known core podocyte signaling pathways, such as mTOR- or Q10-coenzyme-dependent metabolism in podocytopathies with the ultimate goal of novelizing therapeutic approaches in MCD and FSGS.


Volker, L.A., Brinkkoetter, P.T., Knobl, P.N., Krstic, M., Kaufeld, J., Menne, J., Buxhofer-Ausch, V., and Miesbach, W. (2020) Treatment of acquired thrombotic thrombocytopenic purpura without plasma exchange in selected patients under caplacizumab. J Thromb Haemost,  18(11): 3061-3066.

Volker, L.A., Ehren, R., Grundmann, F., Benzing, T., Weber, L.T., and Brinkkotter, P.T. (2019) A newly established clinical registry of minimal change disease and focal and segmental glomerulosclerosis in Germany. Nephrol Dial Transplant,  34(12): 1983-1986.

Volker, L.A., Maar, B.A., Pulido Guevara, B.A., Bilkei-Gorzo, A., Zimmer, A., Bronneke, H., Dafinger, C., Bertsch, S., Wagener, J.R., Schweizer, H., Schermer, B., Benzing, T., and Hoehne, M. (2018) Neph2/Kirrel3 regulates sensory input, motor coordination, and home-cage activity in rodents. Genes Brain Behav,  17(8): e12516.

Voskarides, K., Stefanou, C., Pieri, M., Demosthenous, P., Felekkis, K., Arsali, M., Athanasiou, Y., Xydakis, D., Stylianou, K., Daphnis, E., Goulielmos, G., Loizou, P., Savige, J., Hohne, M., Volker, L.A., Benzing, T., Maxwell, P.H., Gale, D.P., Gorski, M., Boger, C., Kollerits, B., Kronenberg, F., Paulweber, B., Zavros, M., Pierides, A., and Deltas, C. (2017) A functional variant in NEPH3 gene confers high risk of renal failure in primary hematuric glomerulopathies. Evidence for predisposition to microalbuminuria in the general population. PLoS One,  12(3): e0174274.

Rinschen, M.M., Hoppe, A.K., Grahammer, F., Kann, M., Volker, L.A., Schurek, E.M., Binz, J., Hohne, M., Demir, F., Malisic, M., Huber, T.B., Kurschat, C., Kizhakkedathu, J.N., Schermer, B., Huesgen, P.F., and Benzing, T. (2017) N-Degradomic Analysis Reveals a Proteolytic Network Processing the Podocyte Cytoskeleton. J Am Soc Nephrol,  28(10): 2867-2878.

Volker, L.A., Schurek, E.M., Rinschen, M.M., Tax, J., Schutte, B.A., Lamkemeyer, T., Ungrue, D., Schermer, B., Benzing, T., and Hohne, M. (2013) Characterization of a short isoform of the kidney protein podocin in human kidney. BMC Nephrol,  14: 102.

Volker, L.A., Petry, M., Abdelsabour-Khalaf, M., Schweizer, H., Yusuf, F., Busch, T., Schermer, B., Benzing, T., Brand-Saberi, B., Kretz, O., Hohne, M., and Kispert, A. (2012) Comparative analysis of Neph gene expression in mouse and chicken development. Histochem Cell Biol,  137(3): 355-66.