Ursula Klingmüller

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About Ursula Klingmüller:

No description specified

SEEK ID: https://fairdomhub.org/people/474

Location: Germany

ORCID: Not specified

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Project positions

Other Projects: IMOMESIC (German Cancer Research Center (DKFZ)) ; Chronic Liver Disease Progression (LiSyM-DP - Pillar II) (German Cancer Research Center (DKFZ)) ; Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF - Pillar III) (German Cancer Research Center (DKFZ)) ; MS_DILI (German Cancer Research Center (DKFZ))

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ERASysAPP

The main objective of the ERANET proposal Systems Biology Applications - ERASysAPP (app = application = translational systems biology) is to promote multidimensional and complementary European systems biology projects, programmes and research initiatives on a number of selected research topics. Inter alia, ERASysAPP will initiate, execute and monitor a number of joint transnational calls on systems biology research projects with a particular focus on applications - or in other words so called ...

Projects: SysVirDrug, SysMilk, SysMetEx, MetApp, IMOMESIC, WineSys, CropClock, SYSTERACT, XyloCut, RootBook, ROBUSTYEAST, LEANPROT, ErasysApp Funders

Web page: https://www.cobiotech.eu/about-cobiotech/erasysapp

MS_DILI

No description specified

Projects: MS_DILI

Web page: Not specified

LiSyM - Systems Medicine of the Liver

LiSyM (Liver Systems Medicine) represents a research network of German centers and institutions, brought together by a 20 Million Euro funding program of the German Government, in which mathematicians, modelers, pharmacologists, molecular biologists and clinical scientists work together to develop a Systems Medicine approach to study early and advanced liver disease. The aim of this unique research program is to acquire and use new experimental data and data from existing data bases to build ...

Projects: Early Metabolic Injury (LiSyM-EMI - Pillar I), Chronic Liver Disease Progression (LiSyM-DP - Pillar II), Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF - Pillar III), LiSyM Core Infrastructure and Management (LiSyM-PD), Liver Function Diagnostics (LiSyM-LiFuDi - Pillar IV), Model Guided Pharmacotherapy In Chronic Liver Disease (LiSyM-MGP), Multi-Scale Models for Personalized Liver Function Tests (LiSyM-MM-PLF), The Hedgehog Signalling Pathway (LiSyM-JGMMS), Molecular Steatosis - Imaging & Modeling (LiSyM-MSIM), FAIRDOM & LiSyM & de.NBI Data Structuring Training, New LiSyM project

Web page: http://www.lisym.org

IMOMESIC

IMOMESIC - Integrating Modelling of Metabolism and Signalling towards an Application in Liver Cancer

One of the most challenging questions in cancer research is currently the interconnection of metabolism and signalling. An understanding of mechanisms that facilitate the physiological shift towards a proliferative metabolism in cancer cells is considered a major upcoming topic in oncology and is a key activity for future drug development. Due to the complexity of interrelations, a systems biology ...

Programme: ERASysAPP

Public web page: Not specified

Organisms: Homo sapiens

Chronic Liver Disease Progression (LiSyM-DP - Pillar II)

No description specified

Programme: LiSyM - Systems Medicine of the Liver

Public web page: Not specified

Organisms: Homo sapiens, Mus musculus, Rattus norvegicus

Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF - Pillar III)

No description specified

Programme: LiSyM - Systems Medicine of the Liver

Public web page: Not specified

Organisms: Homo sapiens, Mus musculus, Rattus norvegicus

MS_DILI

No description specified

Programme: MS_DILI

Public web page: Not specified

Organisms: Homo sapiens, Mus musculus

German Cancer Research Center (DKFZ)

Country: Germany

City: Heidelberg

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

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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 16:05

Quantitative analysis of amino acid metabolism in liver cancer links glutamate excretion to nucleotide synthesis

IMOMESIC

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Many cancer cells consume glutamine at high rates; counterintuitively, they simultaneously excrete glutamate, the first intermediate in glutamine metabolism. Glutamine consumption has been linked to …

Authors: Avlant Nilsson, Jurgen R. Haanstra, Martin Engqvist, Albert Gerding, Barbara M. Bakker, Ursula Klingmüller, Bas Teusink, Jens Nielsen

Date Published: 27th Apr 2020

Publication Type: Journal

DOI: 10.1073/pnas.1919250117

Citation: Proc Natl Acad Sci USA:201919250

Created: 28th Apr 2020 at 09:39, Last updated: 28th Apr 2020 at 09:40

Excemplify: a flexible template based solution, parsing and managing data in spreadsheets for experimentalists.

SBEpo - Systems Biology of Erythropoietin

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In systems biology, quantitative experimental data is the basis of building mathematical models. In most of the cases, they are stored in Excel files and hosted locally. To have a public database for …

Authors: L. Shi, L. Jong, U. Wittig, P. Lucarelli, M. Stepath, S. Mueller, L. A. D'Alessandro, U. Klingmuller, W. Muller

Date Published: 3rd Apr 2013

Publication Type: Journal

PubMed ID: 23549603

Citation: J Integr Bioinform. 2013 Apr 3;10(2):220. doi: 10.2390/biecoll-jib-2013-220.

Created: 25th Oct 2016 at 14:20, Last updated: 30th Jul 2020 at 15:04

Division of labor by dual feedback regulators controls JAK2/STAT5 signaling over broad ligand range

Molecular Systems Biology

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Cellular signal transduction is governed by multiple feedback mechanisms to elicit robust cellular decisions. The specific contributions of individual feedback regulators, however, remain unclear. Based …

Authors: J. Bachmann, A. Raue, M. Schilling, M. E. Bohm, C. Kreutz, D. Kaschek, H. Busch, N. Gretz, W. D. Lehmann, J. Timmer, U. Klingmuller

Date Published: 2011

Publication Type: Not specified

DOI: 10.1038/msb.2011.50

Citation: Molecular Systems Biology 7(1) : 516

Created: 3rd Mar 2016 at 10:48, Last updated: 10th Mar 2017 at 13:56

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