Metabolic crosstalk in cancer

  • Functional and Structural Genomics
Prof. Dr. Christiane Opitz

Prof. Dr. Christiane Opitz

Evidence emerging in the last years has led to the re-appreciation of the central role of altered cell metabolism in cancer. We have identified a metabolic pathway of the essential amino acid tryptophan as a key element promoting malignant brain tumors.

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Our Research

Tryptophan metabolites activate the dioxin receptor resulting in enhanced invasiveness and clonogenicity of brain tumor cells and increased formation of brain tumors. While the role of the dioxin receptor in cancer biology is well established, the signaling pathways through which the dioxin receptor promotes cancer are poorly understood. Due to the fact that tryptophan metabolites as (patho-)physiologically relevant endogenous dioxin receptor ligands were just identified, the signaling pathways activated by these endogenous dioxin receptor ligands remain elusive. As different dioxin receptor ligands exert diverse biological effects, it is expected that tryptophan metabolites will activate other signaling pathways than the classical and well-studied exogenous ligand dioxin. Inhibition of the dioxin receptor may be a new approach for cancer therapy. Understanding the downstream signaling pathways that are responsible for the tumor-promoting effects of endogenous dioxin receptor activation may identify more specific therapeutic targets for the treatment of tumors that rely on this pathway and and reveal potential biomarkers for monitoring biological activity of these pathways.

In the future we plan to identify the signaling pathways activated by tryptophan degradation in brain tumor cells. Specifically we will analyze the signaling pathways downstream of endogenous dioxin receptor signaling and the signaling pathways activated by tryptophan depletion. In addition we aim to use our expertise in monitoring cancer metabolism for the analysis of nicotinamide metabolism in brain tumors. Preliminary evidence suggests that several enzymes implicated in nicotinamide metabolism are overexpressed in brain tumors. Our group aims at delineating the role of nicotinamide metabolism in brain tumors by targeted metabolomics and bioinformatics approaches using malignant brain tumor cells and tumor stem cells. If the metabolism of nicotinamide is found to be functionally relevant for the malignant phenotype or the treatment resistance of brain tumors, small molecule screens will be performed to identify inhibitors of the respective enzymes. In addition, nicotinamide will be measured in biofluids of brain tumor patients and correlated with the activity of the respective enzymes in the tumor tissue with the aim of identifying biomarkers for the activity of nicotinamide metabolism for future stratification of patients to treatment with inhibitors of this pathway. In addition, “metabolic flux analyses” will be used to model tryptophan and nicotinamide metabolism.

Our Team

Our team is characterized by a clear division of labor while maintaining close collaboration across various disciplines. This structure enables us to work efficiently and facilitates a successful exchange between theory and practice. The department is led by Prof. Dr. Opitz, who is supported in organizational and administrative matters by Ms. Flörchinger. Together, they ensure the smooth coordination of all projects and processes within the department.

A central member of our team is Dr. Prentzell, who plays a key role in overseeing and implementing all lab-related projects. She not only serves as a representative of Prof. Dr. Opitz but also acts as an essential link between different work areas within the lab. Her coordinating role significantly strengthens communication and collaboration within the team.

Another crucial pillar of our department is the bioinformatics team, led by Dr. Sadik and completed by our PhD student Manar Abdalazem. This team allows us to develop theoretical models and data-driven approaches and directly integrate them into practical experiments. Our PhD student Ivana Karabogdan also employs computational models, with a particular focus on structural analyses. The combination of bioinformatics analysis and experimental validation provides a decisive advantage in our research projects.

Our team is further enriched by highly qualified scientists and postdocs, who bring valuable perspectives through their diverse educational backgrounds. Of particular note is Dr. Panitz, who, as a Clinician Scientist, combines both clinical and scientific expertise. Additionally, Dr. Holfelder, Dr. Saharuka, and Dr. Henneberg, as young and motivated researchers, contribute significantly to our research activities and the advancement of our projects.

The primary laboratory work, alongside planning and student integration, is carried out by our dedicated PhD students: Francisco Yanqui Rivera, Sophie Seifert, Deepak Sayeeram, Livnat Barski, and Tim Kühn. They play a crucial role in the practical execution of our research projects and are a driving force behind scientific progress within our team.

Over the years, numerous students have enriched our team. Their contributions to individual projects and their dedication to daily lab work have not only led to valuable scientific insights but have also significantly contributed to our positive and collegial work environment. They are an integral part of our success and team dynamics.

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    Prof. Dr. Christiane Opitz

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    Beate Flörchinger

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    Dr. Mirja Tamara Prentzell

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    Dr. Ahmed Sadik

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    Dr. Verena Panitz

Selected Publications

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Prof. Dr. Christiane Opitz

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