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Prof. Dr. Pietro Ernesto Cippà

Department of Biomedicine
Profiles & Affiliations

Regenerative Nephrology

The kidney is the central regulator of homeostasis and is involved in physiological processes such as blood pressure control, electrolyte and water balance as well as removal of metabolic toxins and waste. The kidney can be damaged by various conditions, including diabetes, ischemia, drug toxicity, and autoimmunity. Since the kidney cannot produce new functional units - called nephrons - after birth, maintaining homeostasis after kidney injury relies on the number of redundant nephrons available at birth, the compensatory adaptation of the remaining nephrons, and kidney repair. Despite the growing global health burden related to kidney disease, the therapeutic options to support kidney repair and avoid kidney failure remain limited, so that kidney replacement therapy by dialysis or transplantation remains the only option for a significant number of patients. Kidney repair depends primarily on cell plasticity: while damaged tubule cells undergo cell death, remaining tubule cells enter a reparative state characterized by the activation of genes involved in cell adhesion, migration, and proliferation. Tubule cell dedifferentiation contributes to altered homeostasis and reduced kidney function following acute kidney injury, but it is a critical initial step of a complex biological process involving the proliferation of reparative cells and their re-differentiation into functional tubule cells. In recent years, we have contributed to fundamental discoveries on the cellular mechanisms of kidney repair. We have characterized the states of epithelial cells involved in kidney repair, elucidated the pivotal role of the transcription factor SOX9 in both kidney repair and fibrosis, and highlighted the central role of altered renal metabolism in acute kidney injury. Our current research aims to identify the critical molecular processes that govern the re-differentiation of reparative tubule cells and to understand the impact of dynamic cell state transitions on the local microenvironment during kidney repair. We are particularly focused on the mechanisms of kidney fibrosis and the interactions between the kidney and the immune system. Our long-term objective is to develop targeted therapies to modulate the repair process and promote kidney regeneration in the contexts of aging, kidney disease, and post-kidney transplantation.

Selected Publications

Aggarwal, Shikhar, Wang, Zhanxiang, Pacheco, David Rincon Fernandez, Rinaldi, Anna, Rajewski, Alex, Callemeyn, Jasper, Van Loon, Elisabet, Lamarthée, Baptiste, Covarrubias, Ambart Ester, Hou, Jean, Yamashita, Michifumi, Akiyama, Haruhiko, Karumanchi, S. Ananth, Svendsen, Clive N., Noble, Paul W., Jordan, Stanley C., Breunig, Joshua J., Naesens, Maarten, Cippà, Pietro E., & Kumar, Sanjeev. (2024). SOX9 switch links regeneration to fibrosis at the single-cell level in mammalian kidneys. Science, 383(6685), 1–14. https://doi.org/10.1126/science.add6371

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Gerhardt, L. M. S., Liu, J., Koppitch, K., Cippà, P. E., & McMahon, A. P. (2021). Single-nuclear transcriptomics reveals diversity of proximal tubule cell states in a dynamic response to acute kidney injury. Proceedings of the National Academy of Sciences of the United States of America, 118(27). https://doi.org/10.1073/pnas.2026684118

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Legouis, D., Ricksten, S.-E., Faivre, A., Verissimo, T., Gariani, K., Verney, C., Galichon, P., Berchtold, L., Feraille, E., Fernandez, M., Placier, S., Koppitch, K., Hertig, A., Martin, P.-Y., Naesens, M., Pugin, J., McMahon, A. P., Cippà, P. E., & de Seigneux, S. (2020). Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality. Nature Metabolism, 2(8), 732–743. https://doi.org/10.1038/s42255-020-0238-1

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Cippà, P. E., Liu, J., Sun, B., Kumar, S., Naesens, M., & McMahon, A. P. (2019). A late B lymphocyte action in dysfunctional tissue repair following kidney injury and transplantation. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-09092-2

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