Christiane Opitz

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About Christiane Opitz:

Clinical Trial Coordinator, Leader WP6 – Clinical Studies and Longitudal Analyses

SEEK ID: https://fairdomhub.org/people/1041

Location: Germany

ORCID: Not specified

Joined: 21st Mar 2018

Expertise: Not specified

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breast cancer estrogen receptor gene expression Kynurenine metabolites qPCR radiotherapy receptor resistance Transcriptomics Tryptophan

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MESI-STRAT

MESI-STRAT: Systems Medicine of Metabolic-Signaling Networks -A New Concept for Breast Cancer Patient Stratification. Breast cancer is a complex disease with high prevalence in the European Union and world-wide. 75%-80 of the patients have estrogen receptor-positive (ER)-positive tumors and are treated with endocrine therapies. Endocrine therapies, which block ER-driven tumor growth, show high efficacy. Yet, a significant proportion of the patients will eventually relapse with metastatic breast ...

Programme: This Project is not associated with a Programme

Public web page: http://www.mesi-strat.eu

Organisms: Homo sapiens, Mus musculus, Rattus norvegicus

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German Cancer Research Center (DKFZ)

Country: Germany

City: Heidelberg

Web page: http://www.dkfz.de/en/index.html

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SOP for human genomic DNA extraction

MESI-STRAT

Standard Operating Procedure for human genomic DNA extraction ( copied from GEO DataSets GSM1375121)

Creators: Olga Krebs, Christiane Opitz

Submitter: Olga Krebs

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Created: 19th Mar 2018 at 11:25, Last updated: 15th May 2023 at 12:58

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The complex biology of aryl hydrocarbon receptor activation in cancer and beyond

MESI-STRAT

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Authors: Christiane A. Opitz, Pauline Holfelder, Mirja Tamara Prentzell, Saskia Trump

Date Published: 1st Oct 2023

Publication Type: Journal

DOI: 10.1016/j.bcp.2023.115798

Citation: Biochemical Pharmacology 216:115798

Created: 28th Nov 2023 at 19:19, Last updated: 28th Nov 2023 at 19:20

Tryptophan depletion sensitizes the AHR pathway by increasing AHR expression and GCN2/LAT1-mediated kynurenine uptake, and potentiates induction of regulatory T lymphocytes

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Abstract Background Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan-dioxygenase (TDO) are enzymes catabolizing the essential amino acid tryptophan into kynurenine. Expression of these enzymes is … frequently observed in advanced-stage cancers and is associated with poor disease prognosis and immune suppression. Mechanistically, the respective roles of tryptophan shortage and kynurenine production in suppressing immunity remain unclear. Kynurenine was proposed as an endogenous ligand for the aryl hydrocarbon receptor (AHR), which can regulate inflammation and immunity. However, controversy remains regarding the role of AHR in IDO1/TDO-mediated immune suppression, as well as the involvement of kynurenine. In this study, we aimed to clarify the link between IDO1/TDO expression, AHR pathway activation and immune suppression. Methods AHR expression and activation was analyzed by RT-qPCR and western blot analysis in cells engineered to express IDO1/TDO, or cultured in medium mimicking tryptophan catabolism by IDO1/TDO. In vitro differentiation of naïve CD4+ T cells into regulatory T cells (Tregs) was compared in T cells isolated from mice bearing different Ahr alleles or a knockout of Ahr, and cultured in medium with or without tryptophan and kynurenine. Results We confirmed that IDO1/TDO expression activated AHR in HEK-293-E cells, as measured by the induction of AHR target genes. Unexpectedly, AHR was also overexpressed on IDO1/TDO expression. AHR overexpression did not depend on kynurenine but was triggered by tryptophan deprivation. Multiple human tumor cell lines overexpressed AHR on tryptophan deprivation. AHR overexpression was not dependent on general control non-derepressible 2 (GCN2), and strongly sensitized the AHR pathway. As a result, kynurenine and other tryptophan catabolites, which are weak AHR agonists in normal conditions, strongly induced AHR target genes in tryptophan-depleted conditions. Tryptophan depletion also increased kynurenine uptake by increasing SLC7A5 (LAT1) expression in a GCN2-dependent manner. Tryptophan deprivation potentiated Treg differentiation from naïve CD4+ T cells isolated from mice bearing an AHR allele of weak affinity similar to the human AHR. Conclusions Tryptophan deprivation sensitizes the AHR pathway by inducing AHR overexpression and increasing cellular kynurenine uptake. As a result, tryptophan catabolites such as kynurenine more potently activate AHR, and Treg differentiation is promoted. Our results propose a molecular explanation for the combined roles of tryptophan deprivation and kynurenine production in mediating IDO1/TDO-induced immune suppression.

Authors: Marie Solvay, Pauline Holfelder, Simon Klaessens, Luc Pilotte, Vincent Stroobant, Juliette Lamy, Stefan Naulaerts, Quentin Spillier, Raphaël Frédérick, Etienne De Plaen, Christine Sers, Christiane A Opitz, Benoit J Van den Eynde, Jingjing Zhu

Date Published: 21st Jun 2023

Publication Type: Journal

DOI: 10.1136/jitc-2023-006728

Citation: J Immunother Cancer 11(6):e006728

Created: 28th Nov 2023 at 19:11, Last updated: 28th Nov 2023 at 19:12

Tryptophan stress activates EGFR-RAS-signaling to MTORC1 and p38/MAPK to sustain translation and AHR-dependent autophagy

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Limited supply and catabolism restrict the essential amino acid tryptophan (Trp) in tumors. How tumors sustain translation under Trp stress remains unclear. Unlike other amino acids, Trp stress activates …

Authors: Pauline Pfänder, Lucas Hensen, Patricia Razquin Navas, Marie Solvay, Mirja Tamara Prentzell, Ahmed Sadik, Alexander M. Heberle, Sophie Seifert, Leon Regin, Tobias Bausbacher, Anna-Sophia Egger, Madlen Hotze, Tobias Kipura, Bianca Berdel, Ivana Karabogdan, Luis F. Somarribas Patterson, Michele Reil, Deepak Sayeeram, Vera Peters, Jose Ramos Pittol, Ineke van ’t Land-Kuper, Teresa Börding, Saskia Trump, Alienke van Pijkeren, Yang Zhang, Fabricio Loayza-Puch, Alexander Kowar, Sönke Harder, Lorenz Waltl, André Gollowitzer, Tetsushi Kataura, Viktor I. Korolchuk, Shad A. Mohammed, Phillipp Sievers, Felix Sahm, Hartmut Schlüter, Andreas Koeberle, Carsten Hopf, Marcel Kwiatkowski, Christine Sers, Benoit J. Van den Eynde, Christiane A. Opitz, Kathrin Thedieck

Date Published: 17th Jan 2023

Publication Type: Journal

DOI: 10.1101/2023.01.16.523931

Citation: biorxiv;2023.01.16.523931v1,[Preprint]

Created: 28th Nov 2023 at 18:55, Last updated: 28th Nov 2023 at 19:04

Hypoxia Routes Tryptophan Homeostasis Towards Increased Tryptamine Production.

Chronic Liver Disease Progression (LiSyM-DP - Pillar II), Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF - Pillar III), MESI-STRAT

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The liver is the central hub for processing and maintaining homeostatic levels of dietary nutrients especially essential amino acids such as tryptophan (Trp). Trp is required not only to sustain protein … synthesis but also as a precursor for the production of NAD, neurotransmitters and immunosuppressive metabolites. In light of these roles of Trp and its metabolic products, maintaining homeostatic levels of Trp is essential for health and well-being. The liver regulates global Trp supply by the immunosuppressive enzyme tryptophan-2,3-dioxygenase (TDO2), which degrades Trp down the kynurenine pathway (KP). In the current study, we show that isolated primary hepatocytes when exposed to hypoxic environments, extensively rewire their Trp metabolism by reducing constitutive Tdo2 expression and differentially regulating other Trp pathway enzymes and transporters. Mathematical modelling of Trp metabolism in liver cells under hypoxia predicted decreased flux through the KP while metabolic flux through the tryptamine branch significantly increased. In line, the model also revealed an increased accumulation of tryptamines under hypoxia, at the expense of kynurenines. Metabolic measurements in hypoxic hepatocytes confirmed the predicted reduction in KP metabolites as well as accumulation of tryptamine. Tdo2 expression in cultured primary hepatocytes was reduced upon hypoxia inducible factor (HIF) stabilisation by dimethyloxalylglycine (DMOG), demonstrating that HIFs are involved in the hypoxic downregulation of hepatic Tdo2. DMOG abrogated hepatic luciferase signals in Tdo2 reporter mice, indicating that HIF stability also recapitulates hypoxic rewiring of Trp metabolism in vivo. Also in WT mice HIF stabilization drove homeostatic Trp metabolism away from the KP towards enhanced tryptamine production, leading to enhanced levels of tryptamine in liver, serum and brain. As tryptamines are the most potent hallucinogens known, the observed upregulation of tryptamine in response to hypoxic exposure of hepatocytes may be involved in the generation of hallucinations occurring at high altitude. KP metabolites are known to activate the aryl hydrocarbon receptor (AHR). The AHR-activating properties of tryptamines may explain why immunosuppressive AHR activity is maintained under hypoxia despite downregulation of the KP. In summary our results identify hypoxia as an important factor controlling Trp metabolism in the liver with possible implications for immunosuppressive AHR activation and mental disturbances.

Authors: S. R. Mohapatra, A. Sadik, S. Sharma, G. Poschet, H. M. Gegner, T. V. Lanz, P. Lucarelli, U. Klingmuller, M. Platten, I. Heiland, C. A. Opitz

Date Published: 8th Mar 2021

Publication Type: Journal

PubMed ID: 33679737

Citation: Front Immunol. 2021 Feb 19;12:590532. doi: 10.3389/fimmu.2021.590532. eCollection 2021.

Created: 15th Nov 2021 at 15:05, Last updated: 8th Dec 2022 at 17:26

IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression

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Aryl hydrocarbon receptor (AHR) activation by tryptophan (Trp) catabolites enhances tumor malignancy and suppresses anti-tumor immunity. The context specificity of AHR target genes has so far impeded …

Authors: Ahmed Sadik, Luis F. Somarribas Patterson, Selcen Öztürk, Soumya R. Mohapatra, Verena Panitz, Philipp F. Secker, Pauline Pfänder, Stefanie Loth, Heba Salem, Mirja Tamara Prentzell, Bianca Berdel, Murat Iskar, Erik Faessler, Friederike Reuter, Isabelle Kirst, Verena Kalter, Kathrin I. Foerster, Evelyn Jäger, Carina Ramallo Guevara, Mansour Sobeh, Thomas Hielscher, Gernot Poschet, Annekathrin Reinhardt, Jessica C. Hassel, Marc Zapatka, Udo Hahn, Andreas von Deimling, Carsten Hopf, Rita Schlichting, Beate I. Escher, Jürgen Burhenne, Walter E. Haefeli, Naveed Ishaque, Alexander Böhme, Sascha Schäuble, Kathrin Thedieck, Saskia Trump, Martina Seiffert, Christiane A. Opitz

Date Published: 1st Sep 2020

Publication Type: Journal

DOI: 10.1016/j.cell.2020.07.038

Citation: Cell 182(5):1252-1270.e34

Created: 23rd Feb 2021 at 10:23, Last updated: 8th Dec 2022 at 17:26

The therapeutic potential of targeting tryptophan catabolism in cancer.

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Based on its effects on both tumour cell intrinsic malignant properties as well as anti-tumour immune responses, tryptophan catabolism has emerged as an important metabolic regulator of cancer progression. …

Authors: C. A. Opitz, L. F. Somarribas Patterson, S. R. Mohapatra, D. L. Dewi, A. Sadik, M. Platten, S. Trump

Date Published: 11th Dec 2019

Publication Type: Journal

PubMed ID: 31819194

Citation: Br J Cancer. 2020 Jan;122(1):30-44. doi: 10.1038/s41416-019-0664-6. Epub 2019 Dec 10.

Created: 23rd Feb 2021 at 10:41, Last updated: 8th Dec 2022 at 17:26

Resistance Exercise Reduces Kynurenine Pathway Metabolites in Breast Cancer Patients Undergoing Radiotherapy

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Purpose: Evidence from preclinical studies and trials in healthy volunteers suggests that exercise may modulate the levels of tryptophan (TRP) metabolites along the kynurenine (KYN) pathway. As KYN and …

Authors: Philipp Zimmer, Martina E. Schmidt, Mirja Tamara Prentzell, Bianca Berdel, Joachim Wiskemann, Karl Heinz Kellner, Jürgen Debus, Cornelia Ulrich, Christiane A. Opitz, Karen Steindorf

Date Published: 25th Sep 2019

Publication Type: Not specified

DOI: 10.3389/fonc.2019.00962

Citation: Front. Oncol. 9 : 673

Created: 1st Oct 2019 at 10:21, Last updated: 8th Dec 2022 at 17:26

Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond

MESI-STRAT

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L-Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is involved in the regulation of immunity, neuronal function and intestinal homeostasis. Imbalances in Trp metabolism in disorders …

Authors: Michael Platten, Ellen A. A. Nollen, Ute F. Röhrig, Francesca Fallarino, Christiane A. Opitz

Date Published: 1st May 2019

Publication Type: Journal

DOI: 10.1038/s41573-019-0016-5

Citation: Nat Rev Drug Discov 18(5):379-401

Created: 1st Oct 2019 at 09:58, Last updated: 8th Dec 2022 at 17:26

The PI3K and MAPK/p38 pathways control stress granule assembly in a hierarchical manner

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All cells and organisms exhibit stress-coping mechanisms to ensure survival. Cytoplasmic protein-RNA assemblies termed stress granules are increasingly recognized to promote cellular survival under …

Authors: Alexander Martin Heberle, Patricia Razquin Navas, Miriam Langelaar-Makkinje, Katharina Kasack, Ahmed Sadik, Erik Faessler, Udo Hahn, Philip Marx-Stoelting, Christiane A Opitz, Christine Sers, Ines Heiland, Sascha Schäuble, Kathrin Thedieck

Date Published: 28th Mar 2019

Publication Type: Not specified

DOI: 10.26508/lsa.201800257

Citation: Life Sci. Alliance 2(2) : e201800257

Created: 19th Nov 2019 at 18:09, Last updated: 8th Dec 2022 at 17:26

Suppression of indoleamine-2,3-dioxygenase 1 expression by promoter hypermethylation in ER-positive breast cancer.

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Kynurenine formation by tryptophan-catabolic indoleamine-2,3-dioxygenase 1 (IDO1) plays a key role in tumor immune evasion and inhibition of IDO1 is efficacious in preclinical models of breast cancer. …

Authors: D. L. Dewi, S. R. Mohapatra, S. Blanco Cabanes, I. Adam, L. F. Somarribas Patterson, B. Berdel, M. Kahloon, L. Thurmann, S. Loth, K. Heilmann, D. Weichenhan, O. Mucke, I. Heiland, P. Wimberger, J. D. Kuhlmann, K. H. Kellner, S. Schott, C. Plass, M. Platten, C. Gerhauser, S. Trump, C. A. Opitz