Center for Molecular Medicine Cologne

Brinkkötter, Paul T | Brähler, Sebastian - B 01

Inflammatory signaling in the PDSS2-model of metabolic podocyte damage – from mouse models to human biopsy analysis


In the kidney, the spectrum of inflammatory diseases is broad, ranging from autoimmune diseases to podocytopathies such as focal segmental glomerulosclerosis (FSGS). Identification of common and distinct immunological pathways is key to understanding glomerular pathophysiology and developing targeted therapies. In the past, we developed mouse models of metabolic stress by introducing a specific mutations in metabolic enzymes. In addition to developing a progressive nephrotic syndrome, these mice develop varying degrees of glomerular inflammation. To understand the pathomechanisms responsible for renal inflammation, we will analyze the landscape of inflammatory mechanisms by flow cytometry, single-cell metabolic profiling and single-cell RNA sequencing. Second, we will deplete key immune cell subsets to determine their contribution to glomerulosclerosis. Finally, we will transfer our findings to the bedside utilizing our recently established glomerular disease biobank and perform targeted proteomic analysis from renal biopsies to identify key proinflammatory molecules in various glomerular diseases. These data are simultaneously complemented by state-of-the art multidimensional imaging techniques to visualize the inflammatory infiltrate associated with glomerular injury and to assign proteomic analysis targets to their subcellular location in the same biopsy sample. We strongly believe that this approach will help us to develop tailored treatment strategies for our patients.

Clinical Relevance

Chronic kidney disease is a significant health and socioeconomic problem. Many inflammatory diseases affect the kidney's filtering unit causing irreversible damage. While immunosuppression remains a mainstay of therapy, lack of knowledge regarding the origins of the inflammatory signal hinders the development of targeted treatment strategies. The proposed studies will examine the contribution of myeloid immune cells in glomerular disease and will therefore make a significant contribution to the understanding of the pathophysiology of these complex diseases. Our project has a strong translational aspect by using state-of-the art proteomics and imaging techniques in order to accelerate the development of precision medicine strategies for our patients.


  • Analysis of immune cell subsets in kidney, spleen and renal lymph nodes
  • Determining the contribution of pro-inflammatory and anti-inflammatory myeloid cells in glomerular diseases
  • Deciphering the contribution of metabolic and inflammatory signaling pathways in glomerular disease by combining targeted proteomics and imaging mass cytometry of human kidney biopsy samples
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  • Butt L, Unnersjö-Jess D, Höhne M, Hahnfeldt R, Reilly D, Rinschen MM, Plagmann I, Diefenhardt P, Brähler S, Brinkkötter PT, Brismar H, Blom H, Schermer B, Benzing T. Super-Resolution Imaging of the Filtration Barrier Suggests a Role for Podocin R229Q in Genetic Predisposition to Glomerular Disease.J Am Soc Nephrol. 2022 Jan;33(1):138-154.
  • Brähler S, Zinselmeyer BH, Raju S, Nitschke M, Suleiman H, Saunders BT, Johnson MW, Böhner AMC, Viehmann SF, Theisen DJ, Kretzer NM, Briseño CG, Zaitsev K, Ornatsky O, Chang Q, Carrero JA, Kopp JB, Artyomov MN, Kurts C, Murphy KM, Miner JH, Shaw AS Opposing Roles of Dendritic Cell Subsets in Experimental GN.J. Am. Soc. Nephrol. 29: 138–154, 2018
  • Viehmann SF, Böhner AMC, Kurts C, Brähler S. The multifaceted role of the renal mononuclear phagocyte system Cell Immunol. 2018 Aug;330:97-104.
  • Brähler S, Yu H, Suleiman H, Krishnan GM, Saunders BT, Kopp JB, Miner JH, Zinselmeyer BH, Shaw AS. Intravital and Kidney Slice Imaging of Podocyte Membrane Dynamics. J Am Soc Nephrol. 2016 Nov;27(11):3285-3290.
Prof. Dr. Paul T Brinkkötter CMMC Cologne
Prof. Dr. Paul T Brinkkötter

Clinic II of Internal Medicine

CMMC - PI - B 01

Publications - Paul T Brinkkötter

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PD Dr. Sebastian Brähler CMMC Cologne
PD Dr. Sebastian Brähler

Clinic II of Internal Medicine - CMMC Research Building

CMMC - PI - CAP 17
CMMC - Co-PI - B 01

+49 221 470 39243

Clinic II of Internal Medicine - CMMC Research Building

Robert-Koch-Str. 21

50931 Cologne

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Curriculum Vitae (CV)

Publications on PubMed

Publications - Sebastian Brähler

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Group Members

Paul Diefenhardt, Johanna Odenthal, Bastian Trinsch, Jasper Nies
PhD student
Claudio Sierra Gonzalez, Marie-Kristin Kroll
Francesco Landini