SFB 1192
Project B8
Identifying pathways and factors causing primary FSGS
Focal segmental glomerulosclerosis (FSGS) is one of the most devastating glomerular diseases. Despite significant efforts to identify circulating factors, disease pathways, biomarkers and treatment targets, the discovery pipeline could not yet close the large unmet need for a better understanding and novel therapeutic solutions. We hypothesize that discoveries have been hampered by the poor clinical stratification of FSGS entities, incomplete understanding of podocyte signalling pathways and the eventually complex and low abundant nature of the predicted circulating FSGS factors. Thus, we did build a highly informative patient sample biobank of primary FSGS cases that massively recurred within the first days after renal transplant (n=45) proofing the existence of disease causing host factors. Furthermore, we generated a systematic podocyte expression atlas and signalling map of unprecedented precision and coverage. Together with the longstanding evidence that recurrent primary FSGS (rpFSGS) is being caused by immune podocyte interactions, we aim to systematically decode signalling pathways and eventual circulating factors by: (1) Characterizing pathways and secreted factors of PBMCs from rpFSGS patients. (2) Identification of podocyte signalling programs induced by rpFSGS patient serum, plasma and transferred immune cells. (3) In silico integration (and subsequent in vivo validation) of immune mediated action (aim 1) and podocyte reaction (aim 2) to predict potential FSGS factors. Collectively, these studies will provide insight into the immune-podocyte interactions, thereby facilitating the discovery of novel biomarkers and therapeutic approaches in FSGS.
Publications
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Microbiota-Induced Type I Interferons Instruct a Poised Basal State of Dendritic Cells.
Schaupp L, Muth S, Rogell L, Kofoed-Branzk M, Melchior F, Lienenklaus S, Ganal-Vonarburg SC, Klein M, Guendel F, Hain T, Schütze K, Grundmann U, Schmitt V, Dorsch M, Spanier J, Larsen PK, Schwanz T, Jäckel S, Reinhardt C, Bopp T, Danckwardt S, Mahnke K, Heinz GA, Mashreghi MF, Durek P, Kalinke U, Kretz O, Huber TB, Weiss S, Wilhelm C, Macpherson AJ, Schild H, Diefenbach A, Probst HC.Cell. 2020 May
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Multi-organ and renal tropism of SARS-CoV-2
Puelles VG, Lütgehetmann M, Lindenmeyer MT, Sperhake JP, Wong MN, Allweiss L, Chilla S, Heinemann A, Nicola Wanner N, Liu S, Braun F, Lu S, Pfefferle S, Schröder AS, Edler C, Gross O, Glatzel M, Wichmann D, Wiech T, Stefan Kluge S, Pueschel K, Aepfelbacher M, Huber TBNew England Journal of Medicine. 2020 May
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COVID-19-associated nephritis: early warning for disease severity and complications?
Gross O, Moerer O, Weber M, Huber TB, Scheithauer SThe Lancet. Published Online 2020 May
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A novel mouse model of phospholipase A2 receptor 1-associated membranous nephropathy mimics podocyte injury in patients
Meyer-Schwesinger C, Tomas NM, Dehde S, Seifert L, Hermans-Borgmeyer I, Wiech T, Koch-Nolte F, Huber TB, Zahner G.Kidney Int. 2020 May
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Cellular and Molecular Probing of Intact Human Organs.
Zhao S, Todorov MI, Cai R, -Maskari RA, Steinke H, Kemter E, Mai H, Rong Z, Warmer M, Stanic K, Schoppe O, Paetzold JC, Gesierich B, Wong MN, Huber TB, Duering M, Bruns OT, Menze B, Lipfert J, Puelles VG, Wolf E, Bechmann I, Ertürk A.Cell. 2020 Feb
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Renal clearance of polymeric nanoparticles by mimicry of glycan surface of viruses.
Wyss PP, Lamichhane SP, Abed A, Vonwil D, Kretz O, Huber TB, Sarem M, Shastri VP. Biomaterials. 2020 Feb
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Podocytes maintain high basal levels of autophagy independent of mtor signaling.
Bork T, Liang W, Yamahara K, Lee P, Tian Z, Liu S, Schell C, Thedieck K, Hartleben B, Patel K, Tharaux PL, Lenoir O, Huber TB. Autophagy. 2019 Dec
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Primary decidual zone formation requires Scribble for pregnancy success in mice.
Yuan J, Aikawa S, Deng W, Bartos A, Walz G, Grahammer F, Huber TB, Sun X, Dey SK. Nat Commun. 2019 Nov
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mTOR-mediated podocyte hypertrophy regulates glomerular integrity in mice and humans.
Puelles VG, van der Wolde JW, Wanner N, Scheppach MW, Cullen-McEwen LA, Bork T, Lindenmeyer MT, Gernhold L, Wong MN, Braun F, Cohen CD, Kett MM, Kuppe C, Kramann R, Saritas T, van Roeyen CR, Moeller MJ, Tribolet L, Rebello R, Sun YB, Li J, Müller-Newen G, Hughson MD, Hoy WE, Person F, Wiech T, Ricardo SD, Kerr PG, Denton KM, Furic L, Huber TB, Nikolic-Paterson DJ, Bertram JF. JCI Insight. 2019 Sep
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Novel 3D analysis using optical tissue clearing documents the evolution of murine rapidly progressive glomerulonephritis.
Puelles VG, Fleck D, Ortz L, Papadouri S, Strieder T, Böhner AMC, van der Wolde JW, Vogt M, Saritas T, Kuppe C, Fuss A, Menzel S, Klinkhammer BM, Müller-Newen G, Heymann F, Decker L, Braun F, Kretz O, Huber TB, Susaki EA, Ueda HR, Boor P, Floege J, Kramann R, Kurts C, Bertram JF, Spehr M, Nikolic-Paterson DJ, Moeller MJ. Kidney Int. 2019 Aug
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Anaerobic Glycolysis Maintains the Glomerular Filtration Barrier Independent of Mitochondrial Metabolism and Dynamics.
Brinkkoetter PT, Bork T, Salou S, Liang W, Mizi A, Özel C, Koehler S, Hagmann HH, Ising C, Kuczkowski A, Schnyder S, Abed A, Schermer B, Benzing T, Kretz O, Puelles VG, Lagies S, Schlimpert M, Kammerer B, Handschin C, Schell C, Huber TBCell Rep. 2019 Apr
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Renal proximal tubular epithelial cells exert immunomodulatory function by driving inflammatory CD4+ T-cell responses.
Breda PC, Wiech T, Meyer-Schwesinger C, Grahammer F, Huber TB, Panzer U, Tiegs G, Neumann K.Am J Physiol Renal Physiol. 2019 Apr
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DNA Methyltransferase 1 Controls Nephron Progenitor Cell Renewal and Differentiation.
Wanner N, Vornweg J, Combes A, Wilson S, Plappert J, Rafflenbeul G, Puelles V, Rahman R, Liwinski T, Lindner S, Grahammer F, Kretz O, Wlodek M, Romano T, Moritz K, Boerries M, Busch H, Bonn S, Little M, Bechtel-Walz W, Huber TJ Am Soc Nephrol.. 2019 Jan
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Development and validation of a renal risk score in ANCA-associated glomerulonephritis
Brix S, Noriega M, Tennstedt P, Vettorazzi E, Busch M, Nitschke M, Jabs W, Özcan F, Wendt R, Hausberg M, Sellin L, Panzer U, Huber T, Waldherr R, Hopfer H, Stahl R, Wiech TKidney Int. 2018 Dec
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ARP3 Controls the Podocyte Architecture at the Kidney Filtration Barrier.
Schell C, Sabass B, Helmstaedter M, Geist F, Abed A, Yasuda-Yamahara M, Sigle A, Maier JI, Grahammer F, Siegerist F, Artelt N, Endlich N, Kerjaschki D, Arnold HH, Dengjel J, Rogg M, Huber TB. Dev Cell. 2018 Dec
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The chemokine receptor CX3CR1 reduces renal injury in mice with angiotensin II induced hypertension
Ahadzadeh E, Rosendahl A, Czesla D, Steffens P, Prüßner L, Meyer-Schwesinger C, Wanner N, Paust H, Huber T, Stahl R, Wiech T, Kurts C, Seniuk A, Ehmke H, Wenzel UAm J Physiol Renal Physiol. 2018 Sep
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Organisation of lymphocytic infiltrates in ANCA-associated glomerulonephritis
Brix S, Noriega M, Herden E, Goldmann B, Langbehn U, Busch M, Jabs W, Steinmetz O, Panzer U, Huber T, Stahl R, Wiech THistopathology. 2018 Jun
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A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes.
Rinschen MM, Gödel M, Grahammer F, Zschiedrich S, Helmstädter M, Kretz O, Zarei M, Braun DA, Dittrich S, Pahmeyer C, Schroder P, Teetzen C, Gee H, Daouk G, Pohl M, Kuhn E, Schermer B, Küttner V, Boerries M, Busch H, Schiffer M, Bergmann C, Krüger M, Hildebrandt F, Dengjel J, Benzing T, Huber TB. Cell Rep. 2018 May
Project-Team
Project Leaders
Prof. Dr. Tobias B. Huber
Prof. Dr. Stefan Bonn
