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.
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.
Clinic II of Internal Medicine
CMMC - PI - B 01
paul.brinkkoetter[at]uk-koeln.de
show more…+49 221 478 30627
+49 221 478 78910
Clinic II of Internal Medicine
Kerpener Str. 62
50937 Cologne
Clinic II of Internal Medicine - CMMC Research Building
CMMC - PI - CAP 17
CMMC - Co-PI - B 01
sebastian.braehler[at]uk-koeln.de
show more…+49 221 470 39243
Clinic II of Internal Medicine - CMMC Research Building
Robert-Koch-Str. 21
50931 Cologne
https://www.kidneyresearchcenter.org/52n31/Inflammatory-cells-and-glomerular-injury.htm
PostDoc
Paul Diefenhardt, Johanna Odenthal, Bastian Trinsch, Jasper Nies
PhD student
Claudio Sierra Gonzalez, Marie-Kristin Kroll
Technician
Francesco Landini