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Prof Dr. rer. nat. Branko Zevnik
in vivo Research Facility
CECAD, University of Cologne
Joseph-Stelzmann-Str. 26
50931 Cologne, Germany
+49 221 478-84055
branko.zevnik@uk-koeln.de

Dr. rer. nat. Astrid Claudia Schauss
CECAD Imaging Facility
CECAD, University of Cologne
Joseph-Stelzmann Str. 26
50931 Cologne, Germany
+49 221 478-84027
aschauss@uni-koeln.de

Dr. rer. nat. Katarzyna Bozek
Center for Molecular Medicine (CMMC)
University of Cologne
Robert-Koch-Strasse 21
50931 Cologne, Germany
+49 221 478 89529
k.bozek@uni-koeln.de

Institution
CECAD, University of Cologne
Joseph-Stelzmann-Straße 26
50931 Cologne, Germany

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Branko Zevnik, Astrid Schauss, Katarzyna Bozek

In vivo models, phenotyping and imaging

The generation and systematic standardized analysis of research models at an organismal level is fundamental for all projects within this consortium. This is coordinated by the Central Project CP2. Dr. Branko Zevnik, head of the in vivo Research Facility (ivRF) at CECAD and his team of the Transgene Service Unit, will support each project to develop sophisticated novel models to investigate podocyte biology and pathophysiology in vivo. These genetic approaches include the combination of different DNA recombinases, multi-cistronic knock-in strategies with 2A-peptides, and CRISPR/Cas technologies with the aim of a podocyte-specific manipulation of gene expression, mimicking human genetic diseases as well as expression of additional transgenes - all in a time and cost-efficient manner.

This in vivo pipeline will be instrumental to fulfill our mission to explore novel therapeutic approaches to treat FSGS. The phenotypic analysis of animal models requires state-of-the-art imaging encompassing electron microscopy as well as light microscopy of histological sections. Organizing acquisition and analysis of images as a central core project adds a significant value to the single projects. This is coordinated by Dr. M. Höhne together with Dr. A. Schauss. The CRU329 has established an OMERO platform, for sharing and interactively exchangeing of imaging data within the consortium. Among other features, a digital nephropathology platform has been established together with Dr. C. Schell, which enables annotation and digital review of kidney biopsies both from animal models and from patients. Another goal of CP2 is the automated analysis of kidney sections from mouse tissue as well as from human kidney biopsies. For this purpose, Dr. K. Bozek will perform a mathematical modeling using computer-based machine learning algorithms

PROJECT RELATED PUBLICATIONS

Höhne, M., Ising, C., Hagmann, H., Völker, L., Brähler, S., Schermer, B., Brinkkötter, P.T., Benzing, T. Light Microscopic Visualization of Podocyte Ultrastructure Demonstrates Oscillating Glomerular Contractions. Am. J. Pathol. 2013 182, 332–338.

Koehler, S., Brähler, S., Braun, F., Hagmann, H., Rinschen, M.M., Späth, M.R., Höhne, M., Wunderlich, F.T., Schermer, B., Benzing, T., Brinkkoetter, P.T. Construction of a viral T2A-peptide based knock-in mouse model for enhanced Cre recombinase activity and fluorescent labeling of podocytes. Kidney International 2017 91, 1510–1517.

Agustian, P.A., Schiffer, M., Gwinner, W., Schäfer, I., Theophile, K., Modde, F., Bockmeyer, C.L., Traeder, J., Lehmann, U., Grosshennig, A., Kreipe, H.H., Bröcker, V., Becker, J.U. Diminished met signaling in podocytes contributes to the development of podocytopenia in transplant glomerulopathy. Am. J. Pathol. 178, 2007–2019 (2011).

Agustian, P.A., Bockmeyer, C.L., Modde, F., Wittig, J., Heinemann, F.M., Brundiers, S., Dämmrich, M.E., Schwarz, A., Birschmann, I., Suwelack, B., Jindra, P.T., Ahlenstiel, T., Wohlschläger, J., Vester, U., Ganzenmüller, T., Zilian, E., Feldkamp, T., Spieker, T., Immenschuh, S., Kreipe, H.H., Bröcker, V., Becker, J.U. Glomerular mRNA expression of prothrombotic and antithrombotic factors in renal transplants with thrombotic microangiopathy. Transplantation 95, 1242–1248 (2013).

Becker, J. U., Hoerning, A., Schmid, K. W. & Hoyer, P. F. Immigrating progenitor cells contribute to human podocyte turnover. Kidney Int. 72, 1468–1473 (2007).

Bockmeyer, C.L., Säuberlich, K., Wittig, J., Eßer, M., Roeder, S.S., Vester, U., Hoyer, P.F., Agustian, P.A., Zeuschner, P., Amann, K., Daniel, C., Becker, J.U. Comparison of different normalization strategies for the analysis of glomerular microRNAs in IgA nephropathy. Sci Rep 6, 31992 (2016).

Meyer-Schwesinger, C., Dehde, S., Klug, P., Becker, J.U., Mathey, S., Arefi, K., Balabanov, S., Venz, S., Endlich, K.H., Pekna, M., Gessner, J.E., Thaiss, F., Meyer, T.N. Nephrotic syndrome and subepithelial deposits in a mouse model of immune-mediated anti-podocyte glomerulonephritis. J. Immunol. 187, 3218–3229 (2011).

Meyer-Schwesinger, C., Lange, C., Bröcker, V., Agustian, P., Lehmann, U., Raabe, A., Brinkmeyer, M., Kobayashi, E., Schiffer, M., Büsche, G., Kreipe, H.H., Thaiss, F., Becker, J.U. Bone marrow-derived progenitor cells do not contribute to podocyte turnover in the puromycin aminoglycoside and renal ablation models in rats. Am. J. Pathol. 178, 494–499 (2011).

Modde, F., Agustian, P.A., Wittig, J., Dämmrich, M.E., Forstmeier, V., Vester, U., Ahlenstiel, T., Froede, K., Budde, U., Wingen, A.M., Schwarz, A., Lovric, S., Kielstein, J.T., Bergmann, C., Bachmann, N., Nagel, M., Kreipe, H.H., Bröcker, V., Bockmeyer, C.L., Becker, J.U. Comprehensive analysis of glomerular mRNA expression of pro- and antithrombotic genes in atypical haemolytic-uremic syndrome (aHUS). Virchows Arch. 462, 455–464 (2013).

Worthmann, K., Peters, I., Kümpers, P., Saleem, M., Becker, J.U., Agustian, P.A., Achenbach, J., Haller, H., Schiffer, M. Urinary excretion of IGFBP-1 and -3 correlates with disease activity and differentiates focal segmental glomerulosclerosis and minimal change disease. Growth Factors 28, 129–138 (2010).