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SFB 1192

Project B8

Identifying pathways and factors causing primary focal segmental glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is a progressive and devastating glomerular disease and a major glomerular reason for end stage renal disease. It is hypothesized that primary FSGS is caused by an unknown circulating (immune) factor, which leads to podocyte injury and disease recurrence after kidney transplantation. In the previous funding period, we established (1) a well-defined patient cohort suffering from an early recurrence of FSGS after kidney transplantation, (2) novel in vitro and in vivo FSGS models, (3) single nucleus analysis pipelines of kidney biopsies and (4) in silico tools for the analysis of multi-omics datasets to unravel novel FSGS-associated regulatory networks. Based on our findings, we now aim to (1) systematically integrate the multi-omics datasets obtained from all models mentioned above; (2) characterize and validate identified common and novel FSGS pathways and circulating factor(s); and (3) implement a pipeline for systematic drug repurposing. Together, this project will facilitate FSGS pathway and treatment discovery and shall exemplify a generalizable translational glomerular disease strategy.

Selected Publications:

  • Optimized protocol for the multiomics processing of cryopreserved human kidney tissue.

    Gies SE, Hänzelmann S, Kylies D, Lassé M, Lagies S, Hausmann F, Khatri R, Zolotarev N, Poets M, Zhang T, Demir F, Billing AM, Quaas J, Meister E, Engesser J, Mühlig AK, Lu S, Liu S, Chilla S, Edenhofer I, Czogalla J, Braun F, Kammerer B, Puelles VG, Bonn S, Rinschen MM, Lindenmeyer M, Huber TB. Am J Physiol Renal Physiol. 2024 Nov

  • Multicytokine-producing CD4+ T cells characterize the livers of patients with NASH.

    Woestemeier A, Scognamiglio P, Zhao Y, Wagner J, Muscate F, Casar C, Siracusa F, Cortesi F, Agalioti T, Müller S, Sagebiel A, Konczalla L, Wahib R, Karstens KF, Giannou AD, Duprée A, Wolter S, Wong MN, Mühlig AK, Bielecka AA, Bansal V, Zhang T, Mann O, Puelles VG, Huber TB, Lohse AW, Izbicki JR, Palm NW, Bonn S, Huber S, Gagliani N. JCI Insight. 2023 Jan

  • The calcium-sensing receptor stabilizes podocyte function in proteinuric humans and mice.

    Mühlig AK, Steingröver J, Heidelbach HS, Wingerath M, Sachs W, Hermans-Borgmeyer I, Meyer-Schwesinger C, Choi HY, Lim BJ, Patry C, Hoffmann GF, Endlich N, Bracke K, Weiß M, Guse AH, Lassé M, Rinschen MM, Braun F, Huber TB, Puelles VG, Schmitt CP, Oh J. Kidney Int. 2022 Jun

  • Podocytes Produce and Secrete Functional Complement C3 and Complement Factor H.

    Mühlig AK*, Keir LS*, Abt JC, Heidelbach HS, Horton R, Welsh GI, Meyer-Schwesinger C, Licht C, Coward RJ, Fester L, Saleem MA, Oh J. J Front Immunol. 2020 Aug

  • Immunohistochemical and serological characterization of membranous nephropathy in children and adolescents.

    Dettmar AK, Wiech T, Kemper MJ, Soave A, Rink M, Oh J, Stahl RAK, Hoxha E. Pediatr Nephrol. 2018 Mar

Project-Team

Project Leaders
Dr. med. PhD Anne K. Mühlig
Prof. Dr. Tobias B. Huber

Co-Workers
Dr. Fabian Braun
Dr. Jan Czogalla
Dr. Sydney Gies