IKP Core Facility

Chemical Analytics & Synthesis

Portrait

Main focus is the development and provision of innovative workflows and methods for mass spectrometric analysis of all types of small molecules and lipids in biological materials. Our established workflows include both targeted quantitative analysis of known exogenous and endogenous substances and metabolites as well as non-targeted metabolomic/lipidomic profiling enabling hypothesis-generating research and biomarker discovery. Currently, targeted methods for more than 250 substances are available for analysis of in vitro systems, tissue or body fluids. A recent expansion of our portfolio is the application of label-free quantitative proteomics for evaluation of protein expression changes. The synthesis lab provides otherwise not available substances, mostly drugs and their metabolites and stable isotope-labeled compounds.

Team

Dr. Ute Hofmann
Head of Chemical Analytics & Synthesis
Tel+49-711-8101-5907
ute.hofmann@ikp-stuttgart.de
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Dr. Thomas Mürdter
Deputy Head at IKP; Research Group Leader Tumor Models & Microenvironment; Head of Chemical Analytics & Synthesis
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Dr. Mathias Haag
Research Group Leader Pharmacometabolomics
Tel+49-711-8101-5429
mathias.haag@ikp-stuttgart.de
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Equipment

Mass spectrometers

 

GC-MS

  • GC-MSD 5975C inert XL, Agilent

LC-MS(-MS)

  • Single Quadrupol 6120 with RRHPLC, Agilent
  • Triple Quadrupol 6460 with UHPLC, Agilent
  • Triple Quadrupol 6495B with UHPLC, Agilent
  • Q-TOF 6550 with UHPLC, Agilent
  • Orbitrap Exploris 480 with FAIMS, VanquishNeo nano-LC or API-MALDI-Imaging, Thermo Fisher Scientific

HPLC Systems

 

  • 2 gradient HPLC systems (Agilent 1100/1200) with UV-Diode array and fluorescence detector, fraction collector
  • Devices for sample preparation

 

Chemical synthesis

 

  • Microwave reactor
  • Preparative flash chromatography & HPLC system

 

Methods

  • Glycolytic metabolites (glucose, pyruvate, lactate, glucose 6-P, glucose 1-P, fructose 6-P, fructose 1,6-P2, 3-phosphoglycerate, phosphoenolpyruvate)
  • Pentose phosphate pathway (6-phosphogluconate, ribulose 5-P, ribose 5-P)
  • TCA cycle (malate, fumarate, citrate, isocitrate, aconitate, 2-oxoglutarate, succinate)
  • Amino acid metabolism (proteinogenic amino acids, ornithine, citrulline, kynurenine, 3-hydroxykynurenine, urea)
  • Ketone bodies (acetoacetate, 3-hydroxybutyrate)
  • Cholesterol biosynthesis and metabolites (mevalonate, lanosterol, lathosterol, cholesterol, 4ß-hydroxycholesterol, 7α-hydroxycholesterol, 24- and 27-hydroxycholesterol)
  • Bile acids (> 25 different human and mouse bile acids incl. sulfates)
  • nucleotides (energy charge, ATP, ADP, AMP, cAMP)
  • nucleosides (modified nucleosides in DNA and RNA for epigenetic investigations)
  • nucleobases (uracil, thymine and metabolites)
  • Lipids (individual triglycerides, phosphatidylcholines, phosphatidylethanolamines and precursors, free fatty acids)
  • Short-chain fatty acids (propionate, butyrate, isobutyrate, valerate, isovalerate, caproate)
  • Steroid hormones (cortisol, 6ß-hydroxycortisol, estradiol, estrone, estrone sulfate, DHEA, DHEAS, testosterone, androstenedione, progesterone, epitestosterone)
  • Polyamine metabolism (putrescine, spermine, spermidine, acetylspermine, diacetylspermidine, acetylspermidine, diacetylspermidine)
  • Acetylcholine
  • Nicotinamide metabolism (nicotinamide, nicotinamide mononucleotide, NAD+, NADH, NADP+, NADPH)
  • Others: creatinine, uric acid, allantoin, glutathione oxidized, N-acetylneuraminic acid
  • 5-ASA (acetyl-5-ASA)
  • 5-fluorouracil (dihydrofluorouracil)
  • amodiaquine (desethyl amodiaquine)
  • Antipyrin (all major metabolites)
  • Antibiotics (meropenem, piperacillin/tazobactam, cefuroxim, flucloxacillin, linezolid, ciprofloxacin, vancomycin, colistin)
  • Antiepileptics (carbamazepine, phenytoin)
  • Antipsychotics, antidepressants and anti-attention-deficit/hyperactivity disorder medications (SSRIs: citalopram, escitalopram, desmethylcitalopram, doxepin, nordoxepin, sertralin, N-desmethylsertralin, paroxetine; tricyclic antidepressants: amitryptiline, nortriptyline, clomipramine, N-desmethylclomipramine, imipramine, desipramine; others: aripiprazole, atomoxetine, clozapine, haloperidol, pimozide, venlafaxine, N-desmethylvenlafaxine, zuclopenthixol)
  • Bindarit
  • Budesonide
  • Bupropion (hydroxybupropion)
  • Caffeine (paraxanthine, 1-methylxanthine, AAMU, AFMU )
  • Clomiphene (>25 metabolites)
  • Clopidogrel
  • Cyclophosphamide
  • Dextromethorphan (dextrorphan, hydroxymorphinan, methoxymorphinan, glucuronides)
  • Digoxin
  • Diphenhydramine (nordiphenhydramine, diphenhydramine-N-glucuronide)
  • Doxorubicin (doxorubicinol)
  • Efavirenz, 8-hydroxyefavirenz
  • Fexofenadine
  • Flecainide
  • Ifosfamide
  • Irinotecan
  • Letrozole (carbinol metabolite, carbinol glucuronide)
  • MAP kinase inhibitors
  • Mefloquine (mefloquine enantiomers, carboxymefloquine)
  • Mephenytoin (nirvanol, 4-hydroxymephenytoin)
  • Metoclopramide (desethyl-metoclopramide (M3), hydroxylamine glucuronide (M7))
  • Metformin
  • Methotrexate (polyglutamates)
  • Metoprolol (α-hydroxymetoprolol)
  • Midazolam (1'-hydroxymidazolam, 4-hydroxymidazolam, 1'-hydroxymidazolam glucuronide)
  • Nabumetone (5 metabolites)
  • Opioids (codeine, morphine, dihydrocodeine and desmethyl and glucuronide metabolites, oxycodone, oxymorphone, tramadol, O-desmethyltramadol)
  • Phenacetine (acetaminophen)
  • Piritramide
  • Pridinol (hydroxylated metabolites)
  • Propafenone (5-hydroxypropafenone, propafenone glucuronide, N-desalkylpropafenone)
  • Proton pump inhibitors (omeprazole, 5-hydroxyomeprazole, omeprazole sulfone, lansoprazole, rabeprazole, tenatoprazole)
  • Remdesivir
  • Riociguat
  • Statins (atorvastatin, lovastatin, simvastatin, pravastatin, rosuvastatin and metabolites)
  • Syrosingopine
  • Talinolol
  • Tamoxifen (endoxifen and further 30 metabolites)
  • Therapeutic antibodies (infliximab and others)
  • Thiopurine drugs (TPMT activity, 6-thioguanine in plasma, 12 nucleotide metabolites in RBC)
  • Tolbutamide (hydroxytolbutamide)
  • Torsemide (hydroxytorsemide)
  • Tyrosine kinase inhibitors (dasatinib, imatinib, N-desmethylimatinib, nilotinib)
  • Verapamil (all major metabolites)
  • Voriconazole
  • Semi-quantitative profiling via RPLC: acylcarnitines, lyso-phospholipids (e.g., lyso-PCs, lyso-PEs), sphingomyelins, ceramides, glycosphingolipids, phosphatidylserines, phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositoles, phosphatidylglyceroles, phosphatidylserines, diacylglycerols, triacylglycerols, cholesterolester, free fatty acids, diketopiperazines
  • Semi-quantitative profiling via HILIC: purine and pyrimidine derivatives and nucleosides, sugar alcohols, monosaccharides, amino acids and derivatives, diketopiperazines, peptides, bile acids, acylcarnitines, lyso-phospholipids (e.g., lyso-PCs, lyso-PEs)
  • (Un)targeted stable isotope-resolved metabolomics with HILIC covering metabolites within glycolysis, TCA cycle and hexosamine pathway, as well as amino acids and derivatives, ribonucleotides, purine and pyrimidine derivatives and nucleosides, glutathione, sialic acids and nucleotide sugars (e.g., UDP-Glucose)

Selected publications of the Core Facility

  • Ghallab A, González D, Strängberg E, Hofmann U, Myllys M, Hassan R, Hobloss Z, Brackhagen L, Begher-Tibbe B, Duda JC, Drenda C, Kappenberg F, Reinders J, Friebel A, Vucur M, Turajski M, Seddek AL, Abbas T, Abdelmageed N, Morad SAF, Morad W, Hamdy A, Albrecht W, Kittana N, Assali M, Vartak N, van Thriel C, Sous A, Nell P, Villar-Fernandez M, Cadenas C, Genc E, Marchan R, Luedde T, Åkerblad P, Mattsson J, Marschall HU, Hoehme S, Stirnimann G, Schwab M, Boor P, Amann K, Schmitz J, Bräsen JH, Rahnenführer J, Edlund K, Karpen SJ, Simbrunner B, Reiberger T, Mandorfer M, Trauner M, Dawson PA, Lindström E, Hengstler JG. Inhibition of the Renal Apical Sodium Dependent Bile Acid Transporter Prevents Cholemic Nephropathy in Mice with Obstructive Cholestasis. J Hepatol. 2023 Nov 6:S0168-8278(23)05235-2. doi: 10.1016/j.jhep.2023.10.035. Epub ahead of print. PMID: 37939855.
  • Nies AT, König J, Leuthold P, Damme K, Winter S, Haag M, Masuda S, Kruck S, Daniel H, Spanier B, Fromm MF, Bedke J, Inui KI, Schwab M, Schaeffeler E. Novel drug transporter substrates identification: An innovative approach based on metabolomic profiling, in silico ligand screening and biological validation. Pharmacol Res. 2023 Oct;196:106941. doi: 10.1016/j.phrs.2023.106941. Epub 2023 Sep 27. PMID: 37775020.
  • Tremmel R, Hofmann U, Haag M, Schaeffeler E, Schwab M. Circulating Biomarkers Instead of Genotyping to Establish Metabolizer Phenotypes. Annu Rev Pharmacol Toxicol. 2023 Aug 16. doi: 10.1146/annurev-pharmtox-032023-121106. Epub ahead of print. PMID: 37585662.
  • Neef SK, Hofmann U, Mürdter TE, Schwab M, Haag M. Performance comparison of narrow-bore and capillary liquid-chromatography for non-targeted metabolomics profiling by HILIC-QTOF-MS. Talanta. 2023 Aug 1;260:124578. doi: 10.1016/j.talanta.2023.124578. Epub 2023 Apr 22. PMID: 37119797.
  • Zhu V, Burhenne J, Weiss J, Haag M, Hofmann U, Schwab M, Urban S, Mikus G, Czock D, Haefeli WE, Blank A. Evaluation of the drug-drug interaction potential of the novel hepatitis B and D virus entry inhibitor bulevirtide at OATP1B in healthy volunteers. Front Pharmacol. 2023 Apr 6;14:1128547. doi: 10.3389/fphar.2023.1128547. PMID: 37089922; PMCID: PMC10117888.
  • Dichamp J, Cellière G, Ghallab A, Hassan R, Boissier N, Hofmann U, Reinders J, Sezgin S, Zühlke S, Hengstler JG, Drasdo D. In vitro to in vivo acetaminophen hepatotoxicity extrapolation using classical schemes, pharmacodynamic models and a multiscale spatial-temporal liver twin. Front Bioeng Biotechnol. 2023 Feb 2;11:1049564. doi: 10.3389/fbioe.2023.1049564. PMID: 36815881; PMCID: PMC9932319.
  • Wedemeyer H, Schöneweis K, Bogomolov P, Blank A, Voronkova N, Stepanova T, Sagalova O, Chulanov V, Osipenko M, Morozov V, Geyvandova N, Sleptsova S, Bakulin IG, Khaertynova I, Rusanova M, Pathil A, Merle U, Bremer B, Allweiss L, Lempp FA, Port K, Haag M, Schwab M, Zur Wiesch JS, Cornberg M, Haefeli WE, Dandri M, Alexandrov A, Urban S. Safety and efficacy of bulevirtide in combination with tenofovir disoproxil fumarate in patients with hepatitis B virus and hepatitis D virus coinfection (MYR202): a multicentre, randomised, parallel-group, open-label, phase 2 trial. Lancet Infect Dis. 2023 Jan;23(1):117-129. doi: 10.1016/S1473-3099(22)00318-8. Epub 2022 Sep 13. PMID: 36113537.
  • Neumann E, Schreeck F, Herberg J, Jacqz Aigrain E, Maitland-van der Zee AH, Pérez-Martínez A, Hawcutt DB, Schaeffeler E, Rane A, de Wildt SN, Schwab M. How paediatric drug development and use could benefit from OMICs: A c4c expert group white paper. Br J Clin Pharmacol. 2022 Dec;88(12):5017-5033. doi: 10.1111/bcp.15216. Epub 2022 Feb 9. PMID: 34997627.
  • Stoll F, Seidel-Glätzer A, Burghaus I, Göring O, Sauter M, Rose P, Daniel V, Haag M, Schwab M, Riffel J, André F, Taylor L, Weiss J, Burhenne J, Cleeves V, Haefeli WE, Blank A. Metabolic Effect of Blocking Sodium-Taurocholate Co-Transporting Polypeptide in Hypercholesterolemic Humans with a Twelve-Week Course of Bulevirtide-An Exploratory Phase I Clinical Trial. Int J Mol Sci. 2022 Dec 14;23(24):15924. doi: 10.3390/ijms232415924. PMID: 36555566; PMCID: PMC9787649.
  • Kube I, Kowalczyk M, Hofmann U, Ghallab A, Hengstler JG, Führer D, Zwanziger D. Hepatobiliary Thyroid Hormone Deficiency Impacts Bile Acid Hydrophilicity and Aquaporins in Cholestatic C57BL/6J Mice. Int J Mol Sci. 2022 Oct 15;23(20):12355. doi: 10.3390/ijms232012355. PMID: 36293210; PMCID: PMC9603918.
  • Lackner M, Neef SK, Winter S, Beer-Hammer S, Nürnberg B, Schwab M, Hofmann U, Haag M. Untargeted stable isotope-resolved metabolomics to assess the effect of PI3Kβ inhibition on metabolic pathway activities in a PTEN null breast cancer cell line. Front Mol Biosci. 2022 Oct 14;9:1004602. doi: 10.3389/fmolb.2022.1004602. PMID: 36310598; PMCID: PMC9614656.
  • Pristup J, Schaeffeler E, Arjune S, Hofmann U, Angel Santamaria-Araujo J, Leuthold P, Friedrich N, Nauck M, Mayr S, Haag M, Muerdter T, Marner FJ, Relling MV, Evans WE, Schwarz G, Schwab M. Molybdenum Cofactor Catabolism Unravels the Physiological Role of the Drug Metabolizing Enzyme Thiopurine S-Methyltransferase. Clin Pharmacol Ther. 2022 Oct;112(4):808-816. doi: 10.1002/cpt.2637. Epub 2022 May 31. PMID: 35538648; PMCID: PMC9474665.
  • Montes-Mojarro IA, Steinhilber J, Griessinger CM, Rau A, Gersmann AK, Kohlhofer U, Fallier-Becker P, Liang HC, Hofmann U, Haag M, Klapper W, Schaeffeler E, Pichler BJ, Schwab M, Fend F, Bonzheim I, Quintanilla-Martinez L. CD147 a direct target of miR-146a supports energy metabolism and promotes tumor growth in ALK+ ALCL. Leukemia. 2022 Aug;36(8):2050-2063. doi: 10.1038/s41375-022-01617-x. Epub 2022 Jun 8. PMID: 35676454.
  • Tremmel R, Nies AT, van Eijck BAC, Handin N, Haag M, Winter S, Büttner FA, Kölz C, Klein F, Mazzola P, Hofmann U, Klein K, Hoffmann P, Nöthen MM, Gaugaz FZ, Artursson P, Schwab M, Schaeffeler E. Hepatic Expression of the Na+-Taurocholate Cotransporting Polypeptide Is Independent from Genetic Variation. Int J Mol Sci. 2022 Jul 5;23(13):7468. doi: 10.3390/ijms23137468. PMID: 35806468; PMCID: PMC9267852.
  • Reustle A, Menig LS, Leuthold P, Hofmann U, Stühler V, Schmees C, Becker M, Haag M, Klumpp V, Winter S, Büttner FA, Rausch S, Hennenlotter J, Fend F, Scharpf M, Stenzl A, Bedke J, Schwab M, Schaeffeler E. Nicotinamide-N-methyltransferase is a promising metabolic drug target for primary and metastatic clear cell renal cell carcinoma. Clin Transl Med. 2022 Jun;12(6):e883. doi: 10.1002/ctm2.883. PMID: 35678045; PMCID: PMC9178377.
  • Ott F, Körner C, Werner K, Gericke M, Liebscher I, Lobsien D, Radrezza S, Shevchenko A, Hofmann U, Kratzsch J, Gebhardt R, Berg T, Matz-Soja M. Hepatic Hedgehog Signaling Participates in the Crosstalk between Liver and Adipose Tissue in Mice by Regulating FGF21. Cells. 2022 May 18;11(10):1680. doi: 10.3390/cells11101680. PMID: 35626717.
  • Weller S, Toennießen A, Schaefer B, Beigl T, Muenchow A, Böpple K, Hofmann U, Gillissen BF, Aulitzky WE, Kopp HG, Essmann F. The BCL-2 inhibitor ABT-199/venetoclax synergizes with proteasome inhibition via transactivation of the MCL-1 antagonist NOXA. Cell Death Discov. 2022 Apr 20;8(1):215. doi: 10.1038/s41420-022-01009-1. PMID: 35443750; PMCID: PMC9021261.
  • Ghallab A, Hassan R, Hofmann U, Friebel A, Hobloss Z, Brackhagen L, Begher-Tibbe B, Myllys M, Reinders J, Overbeck N, Sezgin S, Zühlke S, Seddek AL, Murad W, Brecklinghaus T, Kappenberg F, Rahnenführer J, González D, Goldring C, Copple IM, Marchan R, Longerich T, Vucur M, Luedde T, Urban S, Canbay A, Schreiter T, Trauner M, Akakpo JY, Olyaee M, Curry SC, Sowa JP, Jaeschke H, Hoehme S, Hengstler JG. Interruption of bile acid uptake by hepatocytes after acetaminophen overdose ameliorates hepatotoxicity. J Hepatol. 2022 Feb 4:S0168-8278(22)00062-9. doi: 10.1016/j.jhep.2022.01.020. Epub ahead of print. PMID: 35131407.
  • Heintze T, Wilhelm D, Schmidlin T, Hofmann U, Zanger UM, Schwab M, Klein K. Effects of Diminished NADPH:cytochrome P450 Reductase in Human Hepatocytes on Lipid and Bile Acid Homeostasis. Front Pharmacol. 2021 Nov 15;12:769703. doi: 10.3389/fphar.2021.769703. PMID: 34867397; PMCID: PMC8634102.
  • Ghallab A, Myllys M, Friebel A, Duda J, Edlund K, Halilbasic E, Vucur M, Hobloss Z, Brackhagen L, Begher-Tibbe B, Hassan R, Burke M, Genc E, Frohwein LJ, Hofmann U, Holland CH, González D, Keller M, Seddek AL, Abbas T, Mohammed ESI, Teufel A, Itzel T, Metzler S, Marchan R, Cadenas C, Watzl C, Nitsche MA, Kappenberg F, Luedde T, Longerich T, Rahnenführer J, Hoehme S, Trauner M, Hengstler JG. Spatio-Temporal Multiscale Analysis of Western Diet-Fed Mice Reveals a Translationally Relevant Sequence of Events during NAFLD Progression. Cells. 2021 Sep 23;10(10):2516. doi: 10.3390/cells10102516. PMID: 34685496; PMCID: PMC8533774.
  • Holland CH, Ramirez Flores RO, Myllys M, Hassan R, Edlund K, Hofmann U, Marchan R, Cadenas C, Reinders J, Hoehme S, Seddek AL, Dooley S, Keitel V, Godoy P, Begher-Tibbe B, Trautwein C, Rupp C, Mueller S, Longerich T, Hengstler JG, Saez-Rodriguez J, Ghallab A. Transcriptomic Cross-Species Analysis of Chronic Liver Disease Reveals Consistent Regulation Between Humans and Mice. Hepatol Commun. 2022 Jan;6(1):161-177. doi: 10.1002/hep4.1797. Epub 2021 Aug 28. PMID: 34558834; PMCID: PMC8710791.
  • Hochmuth L, Körner C, Ott F, Volke D, Cokan KB, Juvan P, Brosch M, Hofmann U, Hoffmann R, Rozman D, Berg T, Matz-Soja M. Sex-dependent dynamics of metabolism in primary mouse hepatocytes. Arch Toxicol. 2021 Sep;95(9):3001-3013. doi: 10.1007/s00204-021-03118-9. Epub 2021 Jul 9. PMID: 34241659.
  • Kube I, Tardio LB, Hofmann U, Ghallab A, Hengstler JG, Führer D, Zwanziger D. Hypothyroidism Increases Cholesterol Gallstone Prevalence in Mice by Elevated Hydrophobicity of Primary Bile Acids. Thyroid. 2021 Jan 5. doi: 10.1089/thy.2020.0636. Epub ahead of print. PMID: 33231505.
  • Neef SK, Janssen N, Winter S, Wallisch SK, Hofmann U, Dahlke MH, Schwab M, Mürdter TE, Haag M. Metabolic Drug Response Phenotyping in Colorectal Cancer Organoids by LC-QTOF-MS. Metabolites. 2020 Dec 1;10(12):E494. doi: 10.3390/metabo10120494.
  • Neef SK, Winter S, Hofmann U, Mürdter TE, Schaeffeler E, Horn H, Buck A, Walch A, Hennenlotter J, Ott G, Fend F, Bedke J, Schwab M, Haag M. Optimized protocol for metabolomic and lipidomic profiling in formalin-fixed paraffin-embedded kidney tissue by LC-MS. Anal Chim Acta. 2020 Oct 16;1134:125-135. doi: 10.1016/j.aca.2020.08.005.
  • Reustle A, Di Marco M, Meyerhoff C, Nelde A, Walz JS, Winter S, Kandabarau, S, Büttner F, Haag M, Backert L, Kowalewski DJ, Rausch S, Hennenlotter J, Stühler V, Scharpf M, Fend F, Stenzl A, Rammensee HG, Bedke J, Stevanović S, Schwab M, Schaeffeler E. Integrative -omics and HLA-ligandomics analysis to identify novel drug targets for ccRCC immunotherapy. Genome Med. 2020 Mar 30;12(1):32. doi: 10.1186/s13073-020-00731-8. PMID: 32228647; PMCID: PMC7106651.
  • Luger AL, Lorenz NI, Urban H, Divé I, Engel AL, Strassheimer F, Dettmer K, Zeiner PS, Shaid S, Struve N, Kriegs M, Hofmann U, Oefner PJ, Harter PN, Steinbach JP, Ronellenfitsch MW. Activation of Epidermal Growth Factor Receptor Sensitizes Glioblastoma Cells to Hypoxia-Induced Cell Death. Cancers (Basel). 2020 Aug 3;12(8):E2144. doi: 10.3390/cancers12082144. PMID: 32756332.
  • Asperger H, Stamm N, Gierke B, Pawlak M, Hofmann U, Zanger UM, Marton A, Katona RL, Buhala A, Vizler C, Cieslik JP, Ruckhäberle E, Niederacher D, Fehm T, Neubauer H, Ludescher M. Progesterone receptor membrane component 1 regulates lipid homeostasis and drives oncogenic signaling resulting in breast cancer progression. Breast Cancer Res. 2020 Jul 13;22(1):75. doi: 10.1186/s13058-020-01312-8. PMID: 32660617.
  • Nwosu ZC, Piorońska W, Battello N, Zimmer AD, Dewidar B, Han M, Pereira S, Blagojevic B, Castven D, Charlestin V, Holenya P, Lochead J, De La Torre C, Gretz N, Sajjakulnukit P, Zhang L, Ward MH, Marquardt JU, di Magliano MP, Lyssiotis CA, Sleeman J, Wölfl S, Ebert MP, Meyer C, Hofmann U, Dooley S. Severe metabolic alterations in liver cancer lead to ERK pathway activation and drug resistance. EBioMedicine. 2020;54:102699. doi:10.1016/j.ebiom.2020.102699.
  • Kolbe E, Aleithe S, Rennert C, Spormann L, Ott F, Meierhofer D, Gajowski R, Stöpel C, Hoehme S, Kücken M, Brusch L, Seifert M, von Schoenfels W, Schafmayer C, Brosch M, Hofmann U, Damm G, Seehofer D, Hampe J, Gebhardt R, Matz-Soja M. Mutual Zonated Interactions of Wnt and Hh Signaling Are Orchestrating the Metabolism of the Adult Liver in Mice and Human. Cell Rep. 2019 Dec 24;29(13):4553-4567.e7. doi: 10.1016/j.celrep.2019.11.104. PMID: 31875560.
  • Bruns I, Sauer B, Burger MC, Eriksson J, Hofmann U, Braun Y, Harter PN, Luger AL, Ronellenfitsch MW, Steinbach JP, Rieger J. Disruption of peroxisome proliferator-activated receptor γ coactivator (PGC)-1α reverts key features of the neoplastic phenotype of glioma cells. J Biol Chem. 2019 Mar 1;294(9):3037-3050. doi: 10.1074/jbc.RA118.006993. Epub 2018 Dec 21. PubMed PMID:30578297; PubMed Central PMCID: PMC6398126.
  • Ghallab A, Hofmann U, Sezgin S, Vartak N, Hassan R, Zaza A, Godoy P, Schneider KM, Guenther G, Ahmed YA, Abbas AA, Keitel V, Kuepfer L, Dooley S, Lammert F, Trautwein C, Spiteller M, Drasdo D, Hofmann AF, Jansen PLM, Hengstler JG, Reif R. Bile micro-infarcts in cholestasis are initiated by rupture of the apical hepatocyte membrane and cause shunting of bile to sinusoidal blood. Hepatology. 2019 Feb;69(2):666-683. doi: 10.1002/hep.30213. Epub 2018 Nov 19.
  • Abshagen K, Degenhardt B, Liebig M, Wendt A, Genz B, Schaeper U, Stumvoll M, Hofmann U, Frank M, Vollmar B, Klöting N. Liver-specific Repin1 deficiency impairs transient hepatic steatosis in liver regeneration. Sci Rep. 2018 Nov 15;8(1):16858. doi: 10.1038/s41598-018-35325-3. PubMed PMID: 30442920.
  • Nwosu ZC, Battello N, Rothley M, Piorońska W, Sitek B, Ebert MP, Hofmann U, Sleeman J, Wölfl S, Meyer C, Megger DA, Dooley S. Liver cancer cell lines distinctly mimic the metabolic gene expression pattern of the corresponding human tumours. J Exp Clin Cancer Res. 2018 Sep 3;37(1):211. doi:10.1186/s13046-018-0872-6. Erratum in: J Exp Clin Cancer Res. 2018 Nov 2;37(1):267. PubMed PMID: 30176945; PubMed Central PMCID: PMC6122702.
  • Leuthold P, Schwab M, Hofmann U, Winter S, Rausch S, Pollak MN, Hennenlotter J, Bedke J, Schaeffeler E, Haag M. Simultaneous Extraction of RNA and Metabolites from Single Kidney Tissue Specimens for Combined Transcriptomic and Metabolomic Profiling. J Proteome Res. 2018 Aug 9. doi: 0.1021/acs.jproteome.8b00199. [Epub ahead of print]
  • Heller S, Maurer GD, Wanka C, Hofmann U, Luger AL, Bruns I, Steinbach JP, Rieger J. Gene Suppression of Transketolase-Like Protein 1 (TKTL1) Sensitizes Glioma Cells to Hypoxia and Ionizing Radiation. Int J Mol Sci. 2018 Jul 25;19(8). pii: E2168. doi: 10.3390/ijms19082168.
  • Fujiwara R, Haag M, Schaeffeler E, Nies AT, Zanger UM, Schwab M. Systemic regulation of bilirubin homeostasis: Potential benefits of hyperbilirubinemia. Hepatology. 2018 Apr;67(4):1609-1619. doi: 10.1002/hep.29599. Epub 2018 Mar 2.PMID: 29059457.
  • Schaeffeler E, Büttner F, Reustle A, Klumpp V, Winter S, Rausch S, Fisel P, Hennenlotter J, Kruck S, Stenzl A, Wahrheit J, Sonntag D, Scharpf M, Fend F, Agaimy A, Hartmann A, Bedke J, Schwab M. Metabolic and Lipidomic Reprogramming in Renal Cell Carcinoma Subtypes Reflects Regions of Tumor Origin. Eur Urol Focus. 2019 Jul;5(4):608-618. doi: 10.1016/j.euf.2018.01.016. Epub 2018 Feb 13. PMID: 29452772.
  • Thiepold AL, Lorenz NI, Foltyn M, Engel AL, Divé I, Urban H, Heller S, Bruns I, Hofmann U, Dröse S, Harter PN, Mittelbronn M, Steinbach JP, Ronellenfitsch MW. Mammalian target of rapamycin complex 1 activation sensitizes human glioma cells to hypoxia-induced cell death. Brain. 2017 Oct 1;140(10):2623-2638.
  • Weiss TS, Lupke M, Ibrahim S, Buechler C, Lorenz J, Ruemmele P, Hofmann U, Melter M, Dayoub R. Attenuated lipotoxicity and apoptosis is linked to exogenous and endogenous augmenter of liver regeneration by different pathways. PLoS One. 2017 Sep 6;12(9):e0184282.
  • Rennert C, Eplinius F, Hofmann U, Johänning J, Rolfs F, Schmidt-Heck W, Guthke R, Gebhardt R, Ricken AM, Matz-Soja M. Conditional loss of hepatocellular Hedgehog signaling in female mice leads to the persistence of hepatic steroidogenesis, androgenization and infertility. Arch Toxicol. 2017 Nov;91(11):3677-3687. doi: 10.1007/s00204-017-1999-5. Epub 2017 May 30. PMID: 28560483.
  • Luckert C, Schulz C, Lehmann N, Thomas M, Hofmann U, Hammad S, Hengstler JG, Braeuning A, Lampen A, Hessel S. Comparative analysis of 3D culture methods on human HepG2 cells. Arch Toxicol. 2017 Jan;91(1):393-406.
  • Leuthold P, Schaeffeler E, Winter S, Büttner F, Hofmann U, Mürdter TE, Rausch S, Sonntag D, Wahrheit J, Fend F, Hennenlotter J, Bedke J, Schwab M, Haag M. Comprehensive metabolomic and lipidomic profiling of human kidney tissue: a platform comparison. J Proteome Res. 2017 Feb 3;16(2):933-944. Epub 2016 Dec 19.
  • Godoy P, Widera A, Schmidt-Heck W, Campos G, Meyer C, Cadenas C, Reif R, Stöber R, Hammad S, Pütter L, Gianmoena K, Marchan R, Ghallab A, Edlund K, Nüssler A, Thasler WE, Damm G, Seehofer D, Weiss TS, Dirsch O, Dahmen U, Gebhardt R, Chaudhari U, Meganathan K, Sachinidis A, Kelm J, Hofmann U, Zahedi RP, Guthke R, Blüthgen N, Dooley S, Hengstler JG. Gene network activity in cultivated primary hepatocytes is highly similar to diseased mammalian liver tissue. Arch Toxicol. 2016 Oct;90(10):2513-29.
  • Blank A, Markert C, Hohmann N, Carls A, Mikus G, Lehr T, Alexandrov A, Haag M, Schwab M, Urban S, Haefeli WE. First-in-human application of the novel hepatitis B and hepatitis D virus entry inhibitor myrcludex B. J Hepatol. 2016 Sep;65(3):483-9. doi: 10.1016/j.jhep.2016.04.013. Epub 2016 Apr 27. PMID:27132172.
  • Hocher B, Haumann H, Rahnenführer J, Reichetzeder C, Kalk P, Pfab T, Tsuprykov O, Winter S, Hofmann U, Li J, Püschel GP, Lang F, Schuppan D, Schwab M, Schaeffeler E. Maternal eNOS Deficiency Determines a Fatty Liver Phenotype of the Offspring in a Sex Dependent Manner. Epigenetics. 2016 Jul 2;11(7):539-52. Epub 2016 May 13.
  • Bogomolov P, Alexandrov A, Voronkova N, Macievich M, Kokina K, Petrachenkova M, Lehr T, Lempp FA, Wedemeyer H, Haag M, Schwab M, Haefeli WE, Blank A, Urban S. Treatment of chronic hepatitis D with the entry inhibitor myrcludex B: First results of a phase Ib/IIa study. J Hepatol. 2016 Sep;65(3):490-8. doi:10.1016/j.jhep.2016.04.016. Epub 2016 Apr 27. PMID: 27132170.
  • Ghallab A, Cellière G, Henkel SG, Driesch D, Hoehme S, Hofmann U, Zellmer S, Godoy P, Sachinidis A, Blaszkewicz M, Reif R, Marchan R, Kuepfer L, Häussinger D, Drasdo D, Gebhardt R, Hengstler JG. Model-guided identification of a therapeutic strategy to reduce hyperammonemia in liver diseases. J Hepatol. 2016 Apr;64(4):860-71. Epub 2015 Nov 27. doi: http://dx.doi.org/10.1016/j.jhep.2015.11.018
  • Twardowski L, Cheng F, Michaelsen J, Winter S, Hofmann U, Schaeffeler E, Müller S, Sonnenberg M, Steuer K, Ott G, Schwab M, Franke UF, Torzewski M. Enzymatically Modified Low-Density Lipoprotein Is Present in All Stages of Aortic Valve Sclerosis: Implications for Pathogenesis of the Disease. J Am Heart Assoc. 2015 Oct 16;4(10).
  • Böttger J, Arnold K, Thiel C, Rennert C, Aleithe S, Hofmann U, Vlaic S, Sales S, Shevchenko A, Matz-Soja M. RNAi in murine hepatocytes: the agony of choice-a study of the influence of lipid-based transfection reagents on hepatocyte metabolism. Arch Toxicol. 2015 Sep;89(9):1579-88. Epub 2015 Aug 2.
  • Johänning J, Heinkele G, Precht JC, Brauch H, Eichelbaum M, Schwab M, Schroth W, Mürdter TE. Highly sensitive simultaneous quantification of estrogenic tamoxifen metabolites and steroid hormones by LC-MS/MS. Anal Bioanal Chem. 2015 Sep;407(24):7497-502. doi: 10.1007/s00216-015-8907-8. Epub 2015 Jul 25. PMID: 26206706.
  • Haag M, Hofmann U, Mürdter TE, Heinkele G, Leuthold P, Blank A, Haefeli WE, Alexandrov A, Urban S, Schwab M. Quantitative bile acid profiling by liquid chromatography quadrupole time-of-flight mass spectrometry: monitoring hepatitis B therapy by a novel Na(+)-taurocholate cotransporting polypeptide inhibitor. Anal Bioanal Chem. 2015 Sep;407(22):6815-25. Epub 2015 Jul 5.
  • Lehmann R, Franken H, Dammeier S, Rosenbaum L, Kantartzis K, Peter A, Zell A, Adam P, Li J, Xu G, Königsrainer A, Machann J, Schick F, Hrabé de Angelis M, Schwab M, Staiger H, Schleicher E, Gastaldelli A, Fritsche A, Häring HU, Stefan N. Circulating lysophosphatidylcholines are markers of a metabolically benign nonalcoholic fatty liver. Diabetes Care. 2013 Aug;36(8):2331-8. doi: 10.2337/dc12-1760. Epub 2013 Mar 20. PMID: 23514731; PMCID: PMC3714475.
  • Meyer UA, Zanger UM, Schwab M. Omics and drug response. Annu Rev Pharmacol Toxicol. 2013;53:475-502. doi: 10.1146/annurev-pharmtox-010510-100502. Epub 2012 Nov 5. PMID: 23140244.
  • Potting C, Tatsuta T, König T, Haag M, Wai T, Aaltonen MJ, Langer T. TRIAP1/PRELI complexes prevent apoptosis by mediating intramitochondrial transport of phosphatidic acid. Cell Metab. 2013 Aug 6;18(2):287-95. doi: 10.1016/j.cmet.2013.07.008. PMID: 23931759.
  • Connerth M, Tatsuta T, Haag M, Klecker T, Westermann B, Langer T. Intramitochondrial transport of phosphatidic acid in yeast by a lipid transfer protein. Science. 2012 Nov 9;338(6108):815-8. doi: 10.1126/science.1225625. Epub 2012 Oct 4. PMID: 23042293.
  • Maier K, Hofmann U, Bauer A, Niebel A, Vacun G, Reuss M, Mauch K. Quantification of statin effects on hepatic cholesterol synthesis by transient 13C flux analysis. Metab Eng. 2009 Jul-Sep;11(4-5):292-309.
  • Hofmann U, Maier K, Niebel A, Vacun G, Reuss M, Mauch K. Identification of metabolic fluxes in hepatic cells from transient 13C-labeling experiments: Part I. Experimental observations. Biotechnol Bioeng. 2008 Jun 1;100(2):344-54.