Development of quantitative metabolomics analyses to understand cystic kidney diseases
Final Report Abstract
The role of metabolism is currently shifting from a mere biomarker to an active modulator of biology. The aim of this project was to investigate the role of metabolism in two kidney diseases, cystic kidney disease and hypertensive kidney disease. As an approach the applicant used mass spectrometry-based analysis of small molecules. The applicant learned and contributed to development of both untargeted and targeted metabolomics analyses. In addition, he developed a new pipeline for the analyses of metabolic physiology using isotope labeling. The applicant was able to carry out the metabolomic analyses described above. The applicant received a broad exposure to different metabolomics methods and approaches. Metabolomics analysis were performed for cystic tissue analyses in both untargeted and targeted mass spectrometry assays. The analyses covered metabolites of the TCA cycle and amino acid metabolites. In a second project, the applicant analyzed metabolic rewiring of the hypertensive kidney in both glomerular and tubular compartments. Results depicted metabolic exhaustion in response to mechanical stress and further changes in proximal tubule function. In addition to these metabolomics studies of disease models, the authors were able to establish an in vivo isotope tracing approach that was compatible with untargeted metabolomics analyses.
Publications
- Identification of bioactive metabolites by activity metabolomics. Nat Rev Mol Cell Biol. 2019 Jun;20(6):353-367
Rinschen MM, Ivanesevic J, Giera M, Siuzdak G
(See online at https://doi.org/10.1038/s41580-019-0108-4) - Metabolic rewiring of the hypertensive kidney. Science Signaling, Sci Signal. 2019 Dec 10;12(611)
Rinschen MM, Palygin O, Carlos Guijas C, Palermo A, Nicolas Palacio-Escat N, Xavier Domingo-Almenara X, Rafael Montenegro-Burke R, Julio Saez-Rodriguez J, Staruschenko A, Siuzdak G
(See online at https://doi.org/10.1126/scisignal.aax9760) - Single glomerular proteomics: A novel tool for translational glomerular cell biology Methods Cell Biol. 2019;154:1-14
Rinschen MM
(See online at https://doi.org/10.1016/bs.mcb.2019.03.010) - Podocyte proteome analysis reveals stress responses in glomerular sclerosis. J Am Soc Nephrol. 2020 Mar;31(3):544-559
Koehler S, Kuczkowski A, Kuehne L, Jüngst C, Hoehne M, Grahammer F, Eddy S, Kretzler M, Beck BB, Höhfeld J, Schermer B, Benzing T, Brinkkoetter PT, Rinschen MM
(See online at https://doi.org/10.1681/ASN.2019030312)
