Prof. Dr. med. M. Zeisberg

Renal fibrogenesis

AG Zeisberg

The central focus of our laboratory is to develop novel therapeutic strategies and diagnostic markers to benefit patients with chronic kidney disease. This ambition has translated into three major focus areas in the laboratory: Fibrosis, Regeneration and Kidney disease-related end-organ damage. We address these research areas through a broad range of techniques, embracing cell culture experiments, animal-based research and clinical analyses in an interdisciplinary, international team.

Topics

Chronic kidney disease

More than 10% of the Western population is affected by chronic kidney failure. While chronic kidney disease is often unnoticed during early stages by affected patients, disease progression towards end-stage renal failure requires renal replacement therapies such as dialysis or renal transplantation to circumvent lethality. Even before end-stage renal failure is reached, patients with chronic kidney disease have an increased mortality due increased incidence of cardiovascular, neurological and malignant diseases. Progression of chronic kidney disease is an unsolved biomedical challenge, because neither specific therapies nor reliable biomarkers are available for clinical use. Mechanisms underlying the progression of chronic kidney disease and its associated co-morbidities are central research areas of the Zeisberg laboratory.

 

Fibrosis

Fibrosis is defined as pathological excessive wound-healing process, leading to destruction of organ architecture and to loss of function of the kidney, but also of other organs such as heart, liver or lung. Specific therapies to halt or to even reverse fibrosis are not yet available in the kidney or in any other organ. For this reason we gain mechanistic insights into fibrogenesis, to ultimately benefit patients in the future. Major research areas of our laboratory include epigenetics and DNA-repair mechanisms, which can causally contribute to fibrogenesis.

 

Regeneration

In principle, the kidney possesses a unique capacity to fully regenerate even upon severe acute injury. In clinical reality however, such regenerative capacity is often not realized and pathological fibrosis ensues instead. The clinical relevance of such “Acute-to-chronic kidney injury” is increasingly being recognized. Work of our laboratory aims to restore endogenous regenerative capacity through targeted supplementation of growth factors (i.e. Bone morphogenic protein-7; BMP7), to ultimately benefit affected patients.

 

Kidney disease-related end-organ damage

Chronic kidney disease is associated with increased morbidity and mortality of affected patients. While clinical studies revealed association of chronic renal failure with cardiovascular diseases, cognitive disorders and increased incidence of malignancies, causal mechanisms are still poorly understood. Our current projects explore the role of inorganic phosphate in CKD-associated heart failure and impaired learning as well as the molecular mechanisms underlying malignancies of cystically degenerated kidneys.  

Selected publications

 

  1. Tampe B, Steinle U, Tampe D, Carstens JL, Korsten P, Zeisberg EM, Muller GA, Kalluri R, Zeisberg M: Low-dose hydralazine prevents fibrosis in a murine model of acute kidney injury-to-chronic kidney disease progression, Kidney Int 2017, 91:157-176

  2. Tan X, Xu X, Zeisberg EM, Zeisberg M: High inorganic phosphate causes DNMT1 phosphorylation and subsequent fibrotic fibroblast activation, Biochem Biophys Res Commun 2016, 472:459-464

  3. Lovisa S, LeBleu VS, Tampe B, Sugimoto H, Vadnagara K, Carstens JL, Wu CC, Hagos Y, Burckhardt BC, Pentcheva-Hoang T, Nischal H, Allison JP, Zeisberg M, Kalluri R: Epithelial-to-mesenchymal transition induces cell cycle arrest and parenchymal damage in renal fibrosis, Nat Med 2015, 21:998-1009

  4. Tampe B, Tampe D, Zeisberg EM, Muller GA, Bechtel-Walz W, Koziolek M, Kalluri R, Zeisberg M: Induction of Tet3-dependent Epigenetic Remodeling by Low-dose Hydralazine Attenuates Progression of Chronic Kidney Disease, EBioMedicine 2015, 2:19-36

  5. Tampe B, Tampe D, Muller CA, Sugimoto H, LeBleu V, Xu X, Muller GA, Zeisberg EM, Kalluri R, Zeisberg M: Tet3-mediated hydroxymethylation of epigenetically silenced genes contributes to bone morphogenic protein 7-induced reversal of kidney fibrosis, J Am Soc Nephrol 2014, 25:905-912

  6. Sugimoto H, LeBleu VS, Bosukonda D, Keck P, Taduri G, Bechtel W, Okada H, Carlson W, Jr., Bey P, Rusckowski M, Tampe B, Tampe D, Kanasaki K, Zeisberg M, Kalluri R: Activin-like kinase 3 is important for kidney regeneration and reversal of fibrosis, Nat Med 2012, 18:396-40

  7. Bechtel W, McGoohan S, Zeisberg EM, Muller GA, Kalbacher H, Salant DJ, Muller CA, Kalluri R, Zeisberg M: Methylation determines fibroblast activation and fibrogenesis in the kidney, Nat Med 2010, 16:544-550

  8. Zeisberg EM, Tarnavski O, Zeisberg M, Dorfman AL, McMullen JR, Gustafsson E, Chandraker A, Yuan X, Pu WT, Roberts AB, Neilson EG, Sayegh MH, Izumo S, Kalluri R: Endothelial-to-mesenchymal transition contributes to cardiac fibrosis, Nat Med 2007, 13:952-961

  9. Zeisberg M, Khurana M, Rao VH, Cosgrove D, Rougier JP, Werner MC, Shield CF, Werb Z, Kalluri R: Stage-Specific Action of Matrix Metalloproteinases Influences Progressive Hereditary Kidney Disease, PLoS Med 2006, 3:e100

  10. Zeisberg M, Hanai J, Sugimoto H, Mammoto T, Charytan D, Strutz F, Kalluri R: BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury, Nat Med 2003, 9:964-968

Young Scholar Mentoring

Es ist uns ein wichtiges Anliegen junge Mediziner und Medizinerinnen für Wissenschaft zu begeistern und wissenschaftlich-begeisterte zu fördern. Eingebettet in einem internationalen Team ermöglichen wir Praktika, Labor-Rotationen, Auslands-Austausche, Promotions-Arbeiten und Post-Doc Aufenthalte.

Awards made to young scholars from the Zeisberg Lab

  • 2012: Anschubsförderung der Universitätsmedizin Göttingen an Dr. med. Björn Tampe

  • 2012: Posterpreis der Deutschen Gesellschaft für Innere Medizin an Dr. med. Björn Tampe

  • 2014: Anschubsförderung der Universitätsmedizin Göttingen an Dr. med. Désirée Tampe

  • 2014: Young Investigator Award der International Society of Nephrology an Dr. med. Björn Tampe

  • 2016: Young Investigator Award der Deutschen Gesellschaft für Innere Medizin an Dr. rer. nat. Xiaoying Tan

  • 2016: Vergabe von 3 Reisestipendien der Deutschen Gesellschaft für Innere Medizin an Doktoranden der AG Zeisberg

  • 2016: Bernd Tersteegen Preis des Verbands Deutscher Nierenzentren an Dr. med. Björn Tampe