Cell culture, biochemical assays, proteomics
PhD-Projekt: Functional Proteomics of Gliflozin (Off) targets
Members of the drug class of gliflozins are used to treat diabetic conditions since they inhibit the sodium-glucose cotransporter 2 (SGLT2). This transporter is responsible for the reabsorption of glucose in the kidney where it is mainly expressed . Aside from lowering blood glucose levels, it was shown in different clinical trials and animal studies that in particular one member of this drug class -Empagliflozin- has beneficial effects on metabolic and cardiovascular processes as for instance reducing oxidative stress and cardiovascular disease risk . Due to these new findings, the drug is now even studied in patients without diabetes suffering from cardiovascular diseases.
The aim of my thesis is to understand the underlying mechanism(s) of the cardioprotective effect of Empagliflozin. To achieve this, different cardiomyocyte cell models will be used and functional phenotyping after Empagliflozin treatment will be performed. High resolution mass spectrometry will be employed to observe changes and alterations in protein expression, phospho- and redoxsignaling and the impact of the treatment on the metabolism (proteomics, metabolomics and lipidomics, respectively) next to standard biochemical assays.
 Zelniker T.A. and Braunwald E. Mechanisms of cardiorenal effects of sodium-glucose cotransporter 2 inhibitors. JACC. 75, 422-434 (2020).
 Kolijn, D. et al. Empagliflozin improves endothelial and cardiomyocyte function in human heart failure with preserved ejection fraction via reduced pro-inflammatory-oxidative pathways and protein kinase Ga oxidation. Cardiovascular Research. 117, 495–507 (2021).