Project P3
Modulation of tubular cell transition to a regenerative phenotype
in AKI - diagnostic and therapeutic implications
Prof. Dr. rer. nat. Vera Jankowski, PhD
Institute for Molecular Cardiovascular Research
University hospital RWTH Aachen
E-Mail: vjankowski@ukaachen.de
Eleni Stamellou, PhD, MSc, MD
Department of Nephrology
University hospital RWTH Aachen
E-mail: estamellou@ukaachen.de
The kidney is one of the most heterogeneous organs. Acute tubular injury accounts for the most common intrinsic cause for acute kidney injury (AKI). The “scattered tubular cell” (STC) phenotype was discovered as a uniform reaction of tubule cells triggered by injury. With an inducible transgenic mouse specifically labeling STCs our aim is to validate the relevance and implication of STCs in the course of AKI and to identify markers for AKI progression and outcome. To investigate the STC phenotype and to gain novel insight into the pathophysiology of regeneration and repair upon AKI and transition to CKD we will apply single cell RNA sequencing and proteomic analyses of the STCs using our transgenic PEC-rtTA mice. By this approach, we aim to identify markers of STCs reflecting the stage and the outcome of kidney injury and. Finally we will validate these findings in patients with AKI and CKD. The molecular and clinical expertise of Stamellou will be complemented by the expertise of Jankowski in proteomics to characterize in detail the STC phenotype and its implication in tubular regeneration.
In conclusion, we aim through this promising and innovative approach to improve clinical practice and care for patients with acute kidney injury.
Hermann J, Noels H, Theelen W, Lellig M, Orth-Alampour S, Boor P, Jankowski J, Jankowski V (shared lastauthorship). Sample preparation of formalin-fixed paraffin-embedded tissue sections for MALDI-mass spectrometry imaging. Anal Bioanal Chem. 2020;412:1263-1275
Jankowski V, Saritas T, Kjolby M, Hermann J, Speer T, Himmelsbach A, Mahr K, Heuschkel MA, Schunk SJ, Thirup S, Winther S, Bottcher M, Nyegard M, Nykjaer A, Kramann R, Kaesler N, Jankowski J, Floege J, Marx N, Goettsch C. Carbamylated sortilin associates with cardiovascular calcification in patients with chronic kidney disease. Kidney Int 2022 Mach;101(3):574-584
Schunk SJ, Hermann J, Sarakpi T, Triem S, Lellig M, Hahm E, Zewinger S, Schmit D, Becker E, Möllmann J, Lehrke M, Kramann R, Boor P, Lipp P, Laufs U, März W, Reiser J, Jankowski J, Fliser D, Speer T, Jankowski V. Guanidinylated apolipoprotein C3 (ApoC3) associates with Kidney and vascular injury. J AmSoc Nephrol. 2021 Sep29;32(12):3146-60
Strieder T, Puelles VG, Vogt M, Buhl EM, Saritas T, Hausmann R, Sterzer V, Leuchtle K, Boor P, Floege J, Moeller MJ*, Stamellou E*. Effects of Perfusion Pressures on Podocyte Loss in the Isolated Perfused Mouse Kidney. Cell Physiol Biochem. 2021 Apr 14;55(S4):1-12. doi: 10.33594/000000355.
Stamellou E, Moeller MJ. Regenerating tubular epithelial cells of the kidney. Nephrol Dial Transplant. 2021 Nov 9;36(11):1968-1975. doi: 10.1093/ndt/gfaa103.
Selected Publications