Cell Death Pathways
Team members
Prof. Dr. rer. nat. Stefan Krautwald (PI)
Dr.rer.nat. Theresa Riebeling
Anne Krentz (Technician)
Maja Meßtorff (MD)
Raphael Nische (MD Student)
Annika Hahm (MD)
Isa Alrabea (MD Student)
Stroke, myocardial infarction, sepsis, and acute kidney injury remain significant clinical challenges due to their severe consequences and high mortality rates, even with optimal medical care. Despite advances, effective intervention in the pathophysiological processes that lead to organ damage and patient death remains elusive. A comprehensive understanding of the key molecules involved in these disease processes and the associated cellular signal transduction pathways is crucial for developing significantly improved treatment strategies in the future.
To substantially improve the prognosis for the aforementioned critical conditions, our research group applies molecular biological methods to study and interrupt the cycle of necrotic cell death and inflammation, referred to as “necroinflammation”.
Selected References
Dai E, …, Krautwald S, …, Tang D. A guideline on the molecular ecosystem regulating ferroptosis. Nat Cell Biol. 2024 Sep;26(9):1447-1457.
Kolbrink B, von Samson-Himmelstjerna FA, Murphy JM, Krautwald S. Role of necroptosis in kidney health and disease. Nat Rev Nephrol. 2023 May;19(5):300-314.
Kolbrink B, von Samson-Himmelstjerna FA, Messtorff ML, Riebeling T, Nische R, Schmitz J, Bräsen JH, Kunzendorf U, Krautwald S. Vitamin K1 inhibits ferroptosis and counteracts a detrimental effect of phenprocoumon in experimental acute kidney injury. Cell Mol Life Sci. 2022 Jun 28;79(7):387.
Riebeling T, Jamal K, Wilson R, Kolbrink B, von Samson-Himmelstjerna FA, Moerke C, Ramos Garcia L, Dahlke E, Michels F, Lühder F, Schunk D, Doldi P, Tyczynski B, Kribben A, Flüh C, Theilig F, Kunzendorf U, Meier P, Krautwald S. Primidone blocks RIPK1-driven cell death and inflammation. Cell Death Differ. 2021 May;28(5):1610-1626.
Müller T, Dewitz C, Schmitz J, Schröder AS, Bräsen JH, Stockwell BR, Murphy JM, Kunzendorf U, Krautwald S. Necroptosis and ferroptosis are alternative cell death pathways that operate in acute kidney failure. Cell Mol Life Sci. 2017 Oct;74(19):3631-3645.
Immunity, Metabolism, Kidney and vascular disease
Team members
PD Dr. med. Laura Sievers (PI)
- Eric Amelunxen (MD)
- Bendix Frase (MD Student)
- Anna Schiffer (MD)
- Dr. med. Bettine Steinmann (MD)
Kidney disease and arterial hypertension go along with end organ damage and increased cardiovascular mortality. Inflammatory processes are important drivers of these detrimental long term effects.
We focus on molecular and translational mechanisms of inflammation during kidney disease and cardiovascular complications.
Selected References
Onji M, …, Sievers LK, …, Penninger JM. RANK drives structured intestinal epithelial expansion during pregnancy. Nature. 2025 Jan;637(8044):156-166.
Rüsing S, Welz L, Pfitzer C, Harris DM, Röcken C, Rosenstiel P, Nikolaus S, Tran F, Schreiber S, Aden K, Sievers LK. Decreased Serum Tryptophan and Severe Ulcerative Damage of Colon Mucosa Identify Inflammatory Bowel Disease Patients With High Risk of Cytomegalovirus Colitis. Clin Transl Gastroenterol. 2024 Aug 1;15(8):e00731.
Rüsing S, Welz L, Pfitzer C, Harris DM, Röcken C, Rosenstiel P, Nikolaus S, Tran F, Schreiber S, Aden K, Sievers LK. Decreased Serum Tryptophan and Severe Ulcerative Damage of Colon Mucosa Identify Inflammatory Bowel Disease Patients With High Risk of Cytomegalovirus Colitis. Clin Transl Gastroenterol. 2024 Aug 1;15(8):e00731.
Martini GR, …, Sievers LK, …, Bacher P. Selection of cross-reactive T cells by commensal and food-derived yeasts drives cytotoxic TH1 cell responses in Crohn's disease. Nat Med. 2023 Oct;29(10):2602-2614.
Lepa C, …, Sievers LK, …, George B. TrkC Is Essential for Nephron Function and Trans-Activates Igf1R Signaling. J Am Soc Nephrol. 2021 Feb;32(2):357-374.
Health Care Research
Health Care Research
PD Dr. med. Kevin Schulte (PI)
Dr. med. Benedikt Kolbrink (MD)
Dr. med. Friedrich von Samson-Himmelstjerna (MD)
Christoph Niehus (MD)
Dr. med. Sarah Thomsen (MD)
Our research group examines the healthcare reality of patients with kidney diseases in Germany. To this end, we cooperate with health insurance providers, associations of statutory health insurance physicians, and the Federal Statistical Office. In addition to describing existing deficiencies, our goal is to contribute to the improvement of healthcare structures in Germany based on data-driven insights.
Selected References
von Samson-Himmelstjerna FA, Steiger E, Kolbrink B, Wülfrath HS, Czihal T, Schmitt R, von Stillfried D, Schulte K. Referral, monitoring, and factors associated with non-referral of chronic kidney disease in Germany: a nationwide, retrospective cohort study. Lancet Reg Health Eur. 2024 Oct 31;47:101111.
von Samson-Himmelstjerna FA, Kolbrink B, Budde K, Schmitt R, Schulte K. Continuous donor-recipient age matching: A chance for kidney allocation in the Eurotransplant region. Am J Transplant. 2024 Nov 28:S1600-6135(24)00735-4.
Kolbrink B, Kakavand N, Voran JC, Zacharias HU, Rahmel A, Vogelaar S, Schicktanz S, Braun F, Schmitt R, von Samson-Himmelstjerna FA, Schulte K. Allocation Rules and Age-Dependent Waiting Times for Kidney Transplantation. Dtsch Arztebl Int. 2024 Aug 23;121(17):559-565.
Kolbrink B, Schüssel K, von Samson-Himmelstjerna FA, Esser G, Floege J, Kunzendorf U, Schulte K. Patient-focused outcomes after initiation of dialysis for ESRD: mortality, hospitalization and functional impairment. Nephrol Dial Transplant. 2023 Oct 31;38(11):2528-2536.
Kolbrink B, Scheikholeslami-Sabzewari J, Borzikowsky C, von Samson-Himmelstjerna FA, Ullmann AJ, Kunzendorf U, Schulte K. Evolving epidemiology of pneumocystis pneumonia: Findings from a longitudinal population-based study and a retrospective multi-center study in Germany. Lancet Reg Health Eur. 2022 May 15;18:100400.
Aging Mechanisms and Akute Kidney Injury
Team members
Prof. Dr. med. Roland Schmitt (PI)
Akshaya Balasubramanian (PhD Student)
Vijith Vijayan (PhD)
Katja Bruch (Technician)
We are interested in mechanisms of acute damage and repair in the kidney and in other organs. Our focus is on candidate molecules and signaling pathways that are differentially regulated in an age-dependent manner. In particular, we are interested in novel mechanisms, which impact cell cycle regulation and play a role in the accumulation of senescent cells in kidney, vasculature and other organs.
Selected References
Greite R, …, Schmitt R, …, Vijayan V, …, Immenschuh S. Free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemia. Clin Transl Sci. 2023 Dec;16(12):2729-2743.
Sinning J, Funk ND, Soerensen-Zender I, Wulfmeyer VC, Liao CM, Haller H, Hinze C, Schmidt-Ott KM, Melk A, Schmitt R. The aging kidney is characterized by tubuloinflammaging, a phenotype associated with MHC-II gene expression. Front Immunol. 2023 Aug 22;14:1222339.
Gaedcke S, Sinning J, Dittrich-Breiholz O, Haller H, Soerensen-Zender I, Liao CM, Nordlohne A, Sen P, von Vietinghoff S, DeLuca DS, Schmitt R. Single cell versus single nucleus: transcriptome differences in the murine kidney after ischemia-reperfusion injury. Am J Physiol Renal Physiol. 2022 Aug 1;323(2):F171-F181.
Liao CM, Wulfmeyer VC, Chen R, Erlangga Z, Sinning J, von Mässenhausen A, Sörensen-Zender I, Beer K, von Vietinghoff S, Haller H, Linkermann A, Melk A, Schmitt R. Induction of ferroptosis selectively eliminates senescent tubular cells. Am J Transplant. 2022 Sep;22(9):2158-2168.
Sen P, Helmke A, Liao CM, Sörensen-Zender I, Rong S, Bräsen JH, Melk A, Haller H, von Vietinghoff S, Schmitt R. SerpinB2 Regulates Immune Response in Kidney Injury and Aging. J Am Soc Nephrol. 2020 May;31(5):983-995.