Vätesulfids (H2S) modulatorer: Betydelse i epitel- och endotel- till mesenkymal övergång (EMT & EndoMT)

Tidsperiod: 2019-07-01 till 2022-06-30

Projektledare: MARIA PELELI

Finansiär: Vetenskapsrådet

Bidragstyp: Bidrag för anställning eller stipendier

Budget: 3 150 000 SEK

Epithelial and Endothelial cells are critical for tissue functionality and integrity. Both cell types can be transformed to a more motile and less differentiated (mesenchymal) phenotype, in a process called EMT and EndoMT respectively. EMT and EndoMT can contribute to severe pathologies such as tumor growth and metastasis. TGF-β and ROS signaling induce EMT and EndoMT and finding new molecules that can inhibit these processes is of great importance.H2S is a small, endogenously produced, signaling molecule with antioxidant functions and a suppressive role on TGF-β signaling. However, there is very limited knowledge regarding the role H2S on EMT and EndoMT.Thus, we aim to test the efficacy of H2S modulators on: a) cell models of EMT and EndoMT (6 months, Uppsala University:human cells, 18 moths ,BRFAA, Athens: primary cells from mice KO for H2S biosynthetic enzymes) and b) an animal model of glioblastoma (6 months, Uppsala University). EMT and EndoMT markers will be measured by western blot, fluorescent imaging, RT-PCR and functional assays (wound closure, invasion on 3D cell culture & Matrigel). H2S and ROS levels will be measured by sophisticated methods based on LC MS/MS, chemiluminescence, fluorescence & MitoSOX (6 months, University of Fribourg). Tumor size will be measured by histology.Hopefully, this project will improve our understanding of the molecular events governing EMT and EndoMT and open new therapeutic paths against pathologies such as cancer.