Modeling of metabolic changes in human IDHmut and IDHwt gliomas.
Tryptophan (Trp) is converted into a plethora of metabolites, including well known compounds such as serotonin and melatonin but also kynurenine and NAD. Several metabolites of the Kyn pathway (e.g. the NMDA agonist QA and the antagonist KynA) have neuroactive or signaling function, highlighting the pathophysiological importance of Trp-Kyn-NAD metabolism. In malignant gliomas the Trp pathway plays an important role in promoting malignancy. As part of a collaborative systems medicine effort to establish a network model in malignant glioma, we will focus on integrating experimental data of our partners into theoretical models. We will use this as well as existing expression data to analyze glioma subtype specific changes in metabolism in general and changes in Trp and NAD metabolism in particular. We will furthermore look into particular aspects of metabolite competitions for enzymatic binding sites with an emphasis on how metabolite concentrations are influenced under pathophysiological conditions. The results achieved in this project will allow us to study individual network components as well as their concerted influences on each other. These insights will help us to identify therapeutic targets and their combinations for the treatment of malignant glioma.