Podocytes are highly specialized epithelial cells that maintain the glomerular filtration barrier. Dysregulation of their function is closely linked to the loss of podocyte morphology and contributes to the pathogenesis of various proteinuric kidney diseases, including focal segmental glomerulosclerosis and diabetic nephropathy. We have recently demonstrated that a model of genetic podocyte damage can be significantly improved by depleting monocytes and macrophages, which is surprising, given that genetic defects are typically considered resistant to immunosuppression. Longitudinal single-nucleus RNA sequencing revealed intercellular inflammatory signaling, particularly a connection from monocyte-derived semaphorins to plexins expressed in podocytes.

In this project, we will inestigate how inflammation leads to morphological changes in podocyte structure. To investigate the podocyte-specific function of, we will first examine the expression of plexins and semaphorins in disease models and human kidney biopsies.Next, we will study how how plexins influence the outcome of glomerulonephritis by using a combination of glomerulonephritis models and cell culture.
Lastly, we will evaluate the importance of plexins and semaphorins as accessible therapeutic targets for the specific treatment of podocyte dysfunction in glomerular diseases.

Figure 1

Fig. 1: CYTOF (Cytometry by time of flight) from a patient with chronic kidney disease.

Figure 2

Fig. 2: Imaging Mass Cytometry of a kidney biopsy core. CD16+ Monocytes (white arrow) und CD4+ T-helper cells (red arrow).

Figure 3

Fig. 3: Clustering of glomerular cells by single cell RNAseq.

Figure 4

Fig. 4: Multiphoton imaging of classical dendritic cells (yellow) in crescentic glomerulonephritis (glomeruli in red), collagen fibres in blue

Clinical Relevance

The recent rise in glomerular diseases and chronic kidney diseases has been described as a global health emergency, creating an urgent need for new therapeutic strategies. The morphology of podocytes is not only their most striking anatomical feature, but also critical to their function. Understanding the cellular signaling processes that maintain or disrupt this morphology is essential to understanding podocyte diseases. Our project will clarify, how inflammation leads to podocyte dysfunction and morphological changes. Since cytoskeletal remodeling and loss of podocyte structure (known as foot process effacement) is a common denominator of most glomerular diseases, it is reasonable to speculate that a therapy targeting semaphorins and plexins could be beneficial in various podocyte diseases.

Approach

Single cell RNAsequencing and spatial transcriptomics
Cell culture and mouse knockout models
Superresolution fluorescence imaging and electron microscopy
Flow cytometry and immunohistology
Cell culture and Crispr/ Cas9 genomic editing

Lab Website

For more information, please check Prof. Brinkkötter´s and Dr. Brähler´s site.

Brinkkötter, Paul | Brähler, Sebastian - B 01

Plexin Signaling in Podocyte Disease – Linking Inflammation and Actin Cytoskeleton Remodeling

Prof. Dr. Paul Brinkkötter

PD Dr. Sebastian Brähler

Introduction

Figure 1

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Clinical Relevance

Approach

Lab Website

Affiliations - Paul Brinkkötter

Affiliations - Sebastian Brähler

Publication Record on PubMed - Paul Brinkkötter

Publication Record on PubMed - Sebastian Brähler

Publications generated during 1/2026-12/2028 with CMMC affiliations

2026