Selina Tobien

2025

Master thesis within the study degree of Medical Biotechnology

Malignant pleural mesothelioma (MPM) is an aggressive and nearly incurable cancer, strongly associated with asbestos exposure. Despite its inflammatory nature, the role of lipid mediators (LMs), especially specialized pro-resolving mediators (SPMs), a class of bioactive molecules contributing to inflammation resolution, remains poorly understood. Understanding the cell type-specific regulation of LM synthesis pathways in MPM may reveal novel insights into tumor-promoting inflammation and immune modulation.
This thesis addresses this gap by applying computational pathway analysis to single-cell RNA sequencing data from MPM tumors. LM synthesis pathways were defined using the Atlas of Inflammation Resolution (AIR) and pathway activity was inferred using Hipathia, a systems biology method that integrates gene expression with signaling pathway topology. A range of visualization and clustering techniques were used to explore pathway activity across diverse cell types in the MPM microenvironment.
The analysis revealed unexpected SPM signatures in specific cell types, particularly in mesothelial and T cells and identified an imbalance between PIM and SPM pathway activity in MPM, potentially contributing to sustained inflammation and tumor progression. These findings highlight therapeutic opportunities aimed at restoring pro-resolving functions and emphasize the utility and limitations of transcriptomic pathway analysis for understanding the inflammatory landscape at single-cell resolution.