The role of AHR activation on metabolism and methylation in IDHmut and IDHwt human gliomas.
The ligand-activated aryl hydrocarbon receptor (AHR) is known predominantly for its role in mediating toxic effects of chemicals. However AHR is also involved in (patho-) physiological processes and can be activated by endogenous compounds, for example by tryptophan metabolites (Trp). AHR signaling is therefore closely linked with Trp metabolsm, which is known to promote the aggressiveness of human gliomas. As part of a joint Systems Medicine project to establish a network model in malignant glioma we will specifically elucidate the role of AHR in this context. Consequences of AHR activation will be evaluated on the DNA-, gene-, and protein-level in IDH mutant and wildtype glioma cells. In addition, publically available gene expression and DNA binding studies will be used to establish a glioma-specific AHR activation signature to assess the role of AHR signaling in human glioma tissue. The results achieved in this project will be incorporated into our network model and used for optimization.