Diseases of the kidney filtration barrier are a leading cause of chronic kidney disease and endstage renal failure. The filtration of plasma into primary urine is a highly selective process that takes place in about 1 million filtration units, the glomeruli. The filtration barrier consists of three layers: the fenestrated endothelium of the vasculature, the glomerular basement barrier (GBM) and at the outer aspect of the capillaries, the highly differentiated, glomerular epithelial cell, the podocytes. The latter are solely attached to the GBM and bathed in primary urine. The severity and reversibility of any glomerular disease is defined by the degree of podocyte injury. Loss of podocytes, due to apoptosis or detachment from the glomerular basement membrane, leads to renal/glomerular scarring (Focal Segmental Glomerulosclerosis) and ultimately to the development of kidney failure.
Our research work focuses on the function of podocytes in states of health and disease with special emphasis on metabolic pathways. Basic research and translational questions are addressed using state-of-the-art molecular biological methods/technology and various model-organisms including conditional knock-out and transgenic mice, C. elegans and Drosophila melanogaster. We are currently investigating
Prof. Dr. Paul Brinkkötter
Address of this CAP-CMMC group:
Center for Molecular Medicine Cologne
50931 Köln, Germany
Koehler, S., Kuczkowski, A., Kuehne, L., Jungst, C., Hoehne, M., Grahammer, F., Eddy, S., Kretzler, M., Beck, B.B., Hohfeld, J., Schermer, B., Benzing, T., Brinkkoetter, P.T.*, and Rinschen, M.M.* (2020) Proteome Analysis of Isolated Podocytes Reveals Stress Responses in Glomerular Sclerosis. J Am Soc Nephrol, 31(3): 544-559.
Brinkkoetter, P.T., Bork, T., Salou, S., Liang, W., Mizi, A., Ozel, C., Koehler, S., Hagmann, H.H., Ising, C., Kuczkowski, A., Schnyder, S., Abed, A., Schermer, B., Benzing, T., Kretz, O., Puelles, V.G., Lagies, S., Schlimpert, M., Kammerer, B., Handschin, C., Schell, C., and Huber, T.B. (2019) Anaerobic Glycolysis Maintains the Glomerular Filtration Barrier Independent of Mitochondrial Metabolism and Dynamics. Cell Rep, 27(5): 1551-1566 e5.
Koehler, S., Brahler, S., Braun, F., Hagmann, H., Rinschen, M.M., Spath, M.R., Hohne, M., Wunderlich, F.T., Schermer, B., Benzing, T., and Brinkkoetter, P.T. (2017) Construction of a viral T2A-peptide based knock-in mouse model for enhanced Cre recombinase activity and fluorescent labeling of podocytes. Kidney Int, 91(6): 1510-1517.
Rinschen, M.M., Schroeter, C.B., Koehler, S., Ising, C., Schermer, B., Kann, M., Benzing, T., and Brinkkoetter, P.T. (2016) Quantitative deep mapping of the cultured podocyte proteome uncovers shifts in proteostatic mechanisms during differentiation. Am J Physiol Cell Physiol, 311(3): C404-17.
Koehler, S., Tellkamp, F., Niessen, C.M., Bloch, W., Kerjaschki, D., Schermer, B., Benzing, T., and Brinkkoetter, P.T. (2016) Par3A is dispensable for the function of the glomerular filtration barrier of the kidney. Am J Physiol Renal Physiol, 311(1): F112-9.
Ising, C., Koehler, S., Brahler, S., Merkwirth, C., Hohne, M., Baris, O.R., Hagmann, H., Kann, M., Fabretti, F., Dafinger, C., Bloch, W., Schermer, B., Linkermann, A., Bruning, J.C., Kurschat, C.E., Muller, R.U., Wiesner, R.J., Langer, T., Benzing, T., and Brinkkoetter, P.T. (2015) Inhibition of insulin/IGF-1 receptor signaling protects from mitochondria-mediated kidney failure. EMBO Mol Med, 7(3): 275-87.
Brinkkoetter, P.T., Ising, C., and Benzing, T. (2013). The role of the podocyte in albumin filtration. Nat Rev Nephrol. 9(6): p. 328-36.