Sascha Bulik

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About Sascha Bulik:

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SEEK ID: https://seek.lisym.org/people/41

Location: Germany

ORCID: Not specified

Joined: 18th May 2017

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LiSyM: Liver Systems Medicine

Liver Systems Medicine : striving to develop non-invasive methods for diagnosing and treating NAFLD by combining mathematical modeling and biological research. LiSyM, is a multidisciplinary research network, in which molecular and cell biologists, clinical researchers, pharmacologists and experts in mathematical modeling examine the liver in its entirety. LiSyM research focuses on the metabolic liver disease non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis ...

Projects: LiSyM Core Infrastructure and Management (LiSyM-PD), LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF), LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi), Model Guided Pharmacotherapy In Chronic Liver Disease (LiSyM-MGP), Molecular Steatosis - Imaging & Modeling (LiSyM-MSIM), The Hedgehog Signalling Pathway (LiSyM-JGMMS), Multi-Scale Models for Personalized Liver Function Tests (LiSyM-MM-PLF), LiSyM PALs, Project Management PTJ, LiSyM network, LiSyM Scientific Leadership Team (LiSyM-LT)

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

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LiSyM network: inactive since 2020-03-06

This comprises the whole LiSyM network

Programme: LiSyM: Liver Systems Medicine

Public web page: http://www.lisym.org

Start date: 1st Jan 2016

Organisms: Rattus norvegicus, Rattus rattus, Mus musculus, Homo sapiens

LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi): inactive since 2020-03-06

Disorders of the liver show up through changes in blood tests. These blood tests indicate markers for events taking place in the liver. Usually studies of liver tissue cannot be performed: as liver samples would need to be obtained through a liver biopsy, and this procedure is not without risk, therefore these samples are usually unavailable. Complex metabolism models based on existing and new scientific data can simulate changes in the liver caused by disease. They often reveal unknown relationships ...

Programme: LiSyM: Liver Systems Medicine

Public web page: http://www.lisym.org/our-work/pillar-research/the-liver-is-very-patient

Start date: 1st Jan 2016

Organisms: Homo sapiens

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Charité - Universitätsmedizin Berlin, Institute of Biochemistry, Computational Systems Biochemistry Group

Country: Germany

City: 10117 Berlin

Web page: https://biochemie.charite.de/

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A novel variant of the (13)C-methacetin liver function breath test that eliminates the confounding effect of individual differences in systemic CO2 kinetics.

LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

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The principle of dynamic liver function breath tests is founded on the administration of a (13)C-labeled drug and subsequent monitoring of (13)CO2 in the breath, quantified as time series delta over … natural baseline (13)CO2 (DOB) liberated from the drug during hepatic CYP-dependent detoxification. One confounding factor limiting the diagnostic value of such tests is that only a fraction of the liberated (13)CO2 is immediately exhaled, while another fraction is taken up by body compartments from which it returns with delay to the plasma. The aims of this study were to establish a novel variant of the methacetin-based breath test LiMAx that allows to estimate and to eliminate the confounding effect of systemic (13)CO2 distribution on the DOB curve and thus enables a more reliable assessment of the hepatic detoxification capacity compared with the conventional LiMAx test. We designed a new test variant (named "2DOB") consisting of two consecutive phases. Phase 1 is initiated by the intravenous administration of (13)C-bicarbonate. Phase 2 starts about 30 min later with the intravenous administration of the (13)C-labelled test drug. Using compartment modelling, the resulting 2-phasic DOB curve yields the rate constants for the irreversible elimination and the reversible exchange of plasma (13)CO2 with body compartments (phase 1) and for the detoxification and exchange of the drug with body compartments (phase 2). We carried out the 2DOB test with the test drug (13)C-methacetin in 16 subjects with chronic liver pathologies and 22 normal subjects, who also underwent the conventional LiMAx test. Individual differences in the systemic CO2 kinetics can lead to deviations up to a factor of 2 in the maximum of DOB curves (coefficient of variation CV approximately 0.2) which, in particular, may hamper the discrimination between subjects with normal or mildly impaired detoxification capacities. The novel test revealed that a significant portion of the drug is not immediately metabolized, but transiently taken up into a storage compartment. Intriguingly, not only the hepatic detoxification rate but also the storage capacity of the drug, turned out to be indicative for a normal liver function. We thus used both parameters to define a scoring function which yielded an excellent disease classification (AUC = 0.95) and a high correlation with the MELD score (RSpearman = 0.92). The novel test variant 2DOB promises a significant improvement in the assessment of impaired hepatic detoxification capacity. The suitability of the test for the reliable characterization of the natural history of chronic liver diseases (fatty liver-fibrosis-cirrhosis) has to be assessed in further studies.

Authors: H. G. Holzhutter, T. Wuensch, R. Gajowski, N. Berndt, S. Bulik, D. Meierhofer, M. Stockmann

Date Published: 6th Feb 2020

Publication Type: Not specified

PubMed ID: 32020249

Citation: Arch Toxicol. 2020 Feb;94(2):401-415. doi: 10.1007/s00204-020-02654-0. Epub 2020 Feb 4.

Created: 15th Jun 2020 at 13:32, Last updated: 8th Mar 2024 at 07:44

Kinetic modelling of quantitative proteome data predicts metabolic reprogramming of liver cancer

LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

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Authors: Nikolaus Berndt, Antje Egners, Guido Mastrobuoni, Olga Vvedenskaya, Athanassios Fragoulis, Aurélien Dugourd, Sascha Bulik, Matthias Pietzke, Chris Bielow, Rob van Gassel, Steven W. Olde Damink, Merve Erdem, Julio Saez-Rodriguez, Hermann-Georg Holzhütter, Stefan Kempa, Thorsten Cramer

Date Published: 10th Dec 2019

Publication Type: Not specified

DOI: 10.1038/s41416-019-0659-3

Citation: Br J Cancer 153(16) : 17

Created: 3rd Jan 2020 at 12:20, Last updated: 8th Mar 2024 at 07:44

HEPATOKIN1 is a biochemistry-based model of liver metabolism for applications in medicine and pharmacology.

LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

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The epidemic increase of non-alcoholic fatty liver diseases (NAFLD) requires a deeper understanding of the regulatory circuits controlling the response of liver metabolism to nutritional challenges, …

Authors: N. Berndt, S. Bulik, I. Wallach, T. Wunsch, M. Konig, M. Stockmann, D. Meierhofer, H. G. Holzhutter

Date Published: 21st Jun 2018

Publication Type: Not specified

PubMed ID: 29921957

Citation: Nat Commun. 2018 Jun 19;9(1):2386. doi: 10.1038/s41467-018-04720-9.

Created: 20th Dec 2018 at 10:27, Last updated: 8th Mar 2024 at 07:44

A multiscale modelling approach to assess the impact of metabolic zonation and microperfusion on the hepatic carbohydrate metabolism.

LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

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The capacity of the liver to convert the metabolic input received from the incoming portal and arterial blood into the metabolic output of the outgoing venous blood has three major determinants: The …

Authors: N. Berndt, M. S. Horger, S. Bulik, H. G. Holzhutter

Date Published: 16th Feb 2018

Publication Type: Not specified

PubMed ID: 29447152

Citation: PLoS Comput Biol. 2018 Feb 15;14(2):e1006005. doi: 10.1371/journal.pcbi.1006005. eCollection 2018 Feb.

Created: 20th Dec 2018 at 10:24, Last updated: 8th Mar 2024 at 07:44

The relative importance of kinetic mechanisms and variable enzyme abundances for the regulation of hepatic glucose metabolism--insights from mathematical modeling.

LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

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BACKGROUND: Adaptation of the cellular metabolism to varying external conditions is brought about by regulated changes in the activity of enzymes and transporters. Hormone-dependent reversible enzyme …

Authors: S. Bulik, H. G. Holzhutter, N. Berndt

Date Published: 2nd Mar 2016

Publication Type: Not specified

PubMed ID: 26935066

Citation: BMC Biol. 2016 Mar 2;14:15. doi: 10.1186/s12915-016-0237-6.

Created: 3rd Jul 2020 at 13:55, Last updated: 8th Mar 2024 at 07:44

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Tissue Scale Metabolic Modelling (Sascha Bulik)

LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

Pillar IV Jamboree • (10 min) Introduction to Pillar IV (Hergo Holzhütter) • (20 min) Precise Measurement of Hepatic Elasticity for Fibrosis Detection (Christian Hudert) • (20 min) Tissue Scale Metabolic Modelling (Sascha Bulik) • (10 min) Multi-scale models for liver function tests (Matthias König) • (20 min) Improving the diagnostic precision of the 13C-methacetin dynamic liver function test (LiMAx) (Tilo Wünsch) • (20 min) Mathematical Modelling of Improved Liver Function Breath Test (Hergo ...

Creator: Sascha Bulik

Submitter: Matthias König

Created: 22nd May 2017 at 08:13, Last updated: 22nd May 2017 at 08:32

Poster: Improvement of the Methacetin Breath Test - Sascha Bulik, Wünsch, Th., Gajowski, R., Stockmann, M., Meierhofer, D., and Holzhütter, H.

LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

Creator: Sascha Bulik

Submitter: Matthias König

Created: 22nd May 2017 at 08:19, Last updated: 22nd May 2017 at 08:31

Poster: Tissue scale metabolic modelling - Bulik, S. , Berndt, N. and Holzhütter, H.

LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

Creator: Sascha Bulik

Submitter: Matthias König

Created: 22nd May 2017 at 08:21, Last updated: 22nd May 2017 at 08:31