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Intravital Toxicology

The group uses intravital imaging to investigate toxic mechanisms at the cellular and subcellular level with a strong focus on cholestatic liver diseases.

Head of department
Prof. Dr. Ahmed Ghallab
+49 231 1084-356
Address
Ardeystr. 67
44139 Dortmund

Prof. Dr. Ahmed Ghallab

Group Leader

A key technical achievement of our group is the establishment of a functional two-photon-based intravital imaging toolbox that allows to investigate disease mechanisms at a dynamic, spatially and temporarily resolved cellular and subcellular level. With this, intravital imaging with a spatial resolution of ~200 nm and a temporal resolution in the millisecond rate is possible. Tools are available for intravital imaging of: (i) bile acid transport in health and disease, (ii) blood-bile barrier integrity, (iii) liver immunology and the causal relation to cell death, (iv) mode of cell death and local microenvironment, (v) LPS clearance in health and disease, (vi) toxin transport and clearance, and (vii) inter-organ communication. Besides novel insights into disease pathogenesis, the toolbox allowed us to identify therapeutic options for clinical challenges (se examples below).

 

Imaging tool box
Functional intravital imaging toolbox. A. Bile acid transport. B. Analysis of the blood-bile barrier (BBB) integrity using high molecular weight dextran; left panel: intact BBB in a control mouse; right panel: leaky BBB in an acetaminophen intoxicated mouse. C. Lethal (left panel) versus sublethal (right panel) necroptosis. D. Imaging of immune cell infiltration using reporter mice, specific antibodies, or adoptive transfer. E. Assessment of the phagocytosis function of Kupffer cells using nanoparticles. F. Imaging of the intestine and kidneys.

Interruption of bile acid uptake by hepatocytes after acetaminophen overdose ameliorates hepatotoxicity

Acetaminophen (APAP) overdose is a leading cause of acute liver failure with a limited therapeutic option. It is generally accompanied by increased levels of serum bile acids (BAs). However, the pathophysiological role of BAs remains elusive. Using our imaging toolbox, we investigated the role of BAs in APAP-induced liver injury and identified a therapeutic intervention. In a mouse model, we observed that APAP compromises the blood-bile barrier so that BAs from the bile canaliculi leak into the paracellular space and sinusoidal blood from where they are taken up into hepatocytes, secreted into bile canaliculi and again leak into the sinusoidal blood leading to a process we named ‘futile bile acid cycling’. Consequently, BA concentrations in hepatocytes amount to cytotoxic levels which aggravates APAP-induced liver injury. Interestingly, interruption of BA uptake by hepatocytes - by blocking of the uptake transporters - after APAP overdose strongly ameliorates hepatotoxicity.

Concept bile acid uptake
Concept of targeting the bile acid uptake transporters in hepatocytes to ameliorate acetaminophen hepatotoxicity.

Inhibition of the renal ASBT prevents cholemic nephropathy

Cholemic nephropathy (CN) is a severe complication of cholestasis-associated liver diseases, and no specific treatment is available. To investigate the mechanism and identify therapeutic interventions, we studied the liver-kidney axis in cholestasis using our intravital imaging toolbox. In the acute phase after bile duct ligation (BDL) in mice, bile infarcts are formed by rupture of the apical hepatocyte membrane, and cause shunting of bile to the sinusoidal blood. In the chronic phase after BDL, several adaptive mechanisms are established that limit BA load in hepatocytes but further increase it in the systemic blood.

Concept of bile infarct formation
Concept of bile infarct formation by rupture of the apical hepatocyte membrane and the systemic consequences.

Flooding of the systemic circulation with bile acids in cholestasis coincides with the development of CN; however, the driving mechanism of CN was not clear. Using our imaging tools, we show that BA are reabsorbed from the renal tubular lumen into proximal renal tubular epithelial cells (TEC) and that BA enrichment in TEC is followed by oxidative stress and cell death, damage of peritubular capillaries and massive leakage of BA into the renal interstitium, and fibrosis. Based on this mechanism we used a systemically bioavailable inhibitor that blocks the renal apical sodium-dependent bile acid transporter (ASBT); consequently, urinary excretion of BA was massively enhanced, which not only prevented CN but also systemically reduced BA concentrations. Preserved ASBT expression in human TEC was demonstrated in biopsies from CN patients, highlighting the translational potential of treating CN by targeting ASBT.

Concept of renal ASBT inhibition
Concept of renal ASBT inhibition to treat cholemic nephropathy.
Team
Group picture

Prof. Dr. Ahmed Ghallab

Group leader

 

Dr. Reham Hassan

Main focus: Drug-induced liver injury (DILI)
  Mycotoxins

 

M.Sc. Zaynab Hobloss

Main focus: Liver-brain axis in chronic liver diseases

 

Dr. Daniela González

Main focus: Liver-kidney axis in cholestatic liver disease

 

Dr. Maiju Myllys

Main focus: Metabolic dysfunction-associated steatotic liver disease (MASLD)
  Acute-on-chronic liver injury

 

Ms. Hannah Schmidt

Technical assistant

Third Party Funding

2023-2026: 377,000.00 €, DFG/ Functional imaging to explore a so far unconsidered mechanism of acetaminophen hepatotoxicity.

2021-2024: 477,300.00 € DFG/ NAFLD-NASH-HCC progression: mechanisms of stage-transitions and identification of time windows for prevention.

2016-2021: 1,276,732.00 €, BMBF/ LiSym-MGP: model-guided pharmacotherapy in chronic liver disease

Publications

2024

  1. Ghallab, A., Gonzalez, E. Strangberg, U. Hofmann, M. Myllys, R. Hassan, Z. Hobloss, L. Brackhagen, B. Begher-Tibbe, J. C. Duda, C. Drenda, F. Kappenberg, J. Reinders, A. Friebel, M. Vucur, M. Turajski, A. L. Seddek, T. Abbas, N. Abdelmageed, S. A. F. Morad, W. Morad, A. Hamdy, W. Albrecht, N. Kittana, M. Assali, N. Vartak, C. van Thriel, A. Sous, P. Nell, M. Villar-Fernandez, C. Cadenas, E. Genc, R. Marchan, T. Luedde, P. Akerblad, J. Mattsson, H. U. Marschall, S. Hoehme, G. Stirnimann, M. Schwab, P. Boor, K. Amann, J. Schmitz, J. H. Brasen, J. Rahnenfuhrer, K. Edlund, S. J. Karpen, B. Simbrunner, T. Reiberger, M. Mandorfer, M. Trauner, P. A. Dawson, E. Lindstrom, and J. G. Hengstler. "Inhibition of the Renal Apical Sodium Dependent Bile Acid Transporter Prevents Cholemic Nephropathy in Mice with Obstructive Cholestasis." Journal of Hepatology 80, no. 2 (2024): 268-281. https://dx.doi.org/10.1016/j.jhep.2023.10.035.
  1. Burbano de Lara, S., S. Kemmer, I. Biermayer, S. Feiler, A. Vlasov, L. A. D'Alessandro, B. Helm, C. Mölders, Y. Dieter, Ghallab, J. G. Hengstler, C. Körner, M. Matz-Soja, C. Götz, G. Damm, K. Hoffmann, D. Seehofer, T. Berg, M. Schilling, J. Timmer, and U. Klingmüller. "Basal Met Phosphorylation Is an Indicator of Hepatocyte Dysregulation in Liver Disease." Mol Syst Biol (Jan 12 2024). https://dx.doi.org/10.1038/s44320-023-00007-4.

2023

  1. Vucur, M., Ghallab, A. T. Schneider, A. Adili, M. Cheng, M. Castoldi, M. T. Singer, V. Buttner, L. S. Keysberg, L. Kusgens, M. Kohlhepp, B. Gorg, S. Gallage, J. E. Barragan Avila, K. Unger, C. Kordes, A. L. Leblond, W. Albrecht, S. H. Loosen, C. Lohr, M. S. Jordens, A. Babler, S. Hayat, D. Schumacher, M. T. Koenen, O. Govaere, M. V. Boekschoten, S. Jors, C. Villacorta-Martin, V. Mazzaferro, J. M. Llovet, R. Weiskirchen, J. N. Kather, P. Starlinger, M. Trauner, M. Luedde, L. R. Heij, U. P. Neumann, V. Keitel, J. G. Bode, R. K. Schneider, F. Tacke, B. Levkau, T. Lammers, G. Fluegen, T. Alexandrov, A. L. Collins, G. Nelson, F. Oakley, D. A. Mann, C. Roderburg, T. Longerich, A. Weber, A. Villanueva, A. L. Samson, J. M. Murphy, R. Kramann, F. Geisler, I. G. Costa, J. G. Hengstler, M. Heikenwalder, and T. Luedde. "Sublethal Necroptosis Signaling Promotes Inflammation and Liver Cancer." Immunity 56, no. 7 (2023): 1578-95 e8. https://dx.doi.org/10.1016/j.immuni.2023.05.017. 
  1. Zhao, J, Ghallab, R. Hassan, S. Dooley, J.G. Hengstler, and D. Drasdo. "A Liver Digital Twin for in Silico Testing of Cellular and Inter-Cellular Mechanisms in Regeneration after Drug-Induced Damage." iScience (2023): 108077. https://dx.doi.org/https://doi.org/10.1016/j.isci.2023.108077. 
  1. Fendt R, Ghallab A, Myllys M, Hofmann U, Hassan R, Hobloss Z, González D, Brackhagen L, Marchan R, Edlund K, Seddek A-L, Abdelmageed N, Blank LM, Schlender J-F, Holland CH, Hengstler JG and Kuepfer L. Increased sinusoidal export of drug glucuronides is a compensative mechanism in liver cirrhosis of mice. Frontiers in Pharmacology (2023).doi: 10.3389/fphar.2023.1279357.
  2. Abdelmageed, N., W. A. Twafik, O. A. Morad, M. Haridy, Hassan, M. Ahmed, H. Y. El-Zorba, H. A. El-Banna, A. L. Seddek, A. Ghallab, and S. A. F. Morad. "Vinpocetine Protects against Chloroquine-Induced Cardiotoxicity by Mitigating Oxidative Stress." Archives of Toxicology 97, no. 10 (2023): 2763-70. https://dx.doi.org/10.1007/s00204-023-03546-9. 
  1. Bloch, D., P. Diel, B. Epe, M. Hellwig, A. Lampen, A. Mally, D. Marko, M. A. Villar Fernandez, S. Guth, A. Roth, R. Marchan, Ghallab, C. Cadenas, P. Nell, N. Vartak, C. van Thriel, A. Luch, S. Schmeisser, M. Herzler, R. Landsiedel, M. Leist, P. Marx-Stoelting, T. Tralau, and J. G. Hengstler. "Basic Concepts of Mixture Toxicity and Relevance for Risk Evaluation and Regulation." Archives of Toxicology 97, no. 11 (2023): 3005-17. https://dx.doi.org/10.1007/s00204-023-03565-6. 
  1. Custodio, R. J. P., Hobloss, M. Myllys, R. Hassan, D. Gonzalez, J. Reinders, J. Bornhorst, A. K. Weishaupt, A. L. Seddek, T. Abbas, A. Friebel, S. Hoehme, S. Getzmann, J. G. Hengstler, C. van Thriel, and A. Ghallab. "Cognitive Functions, Neurotransmitter Alterations, and Hippocampal Microstructural Changes in Mice Caused by Feeding on Western Diet." Cells 12, no. 18 (2023). https://dx.doi.org/10.3390/cells12182331. 
  1. Dichamp, J., G. Celliere, Ghallab, R. Hassan, N. Boissier, U. Hofmann, J. Reinders, S. Sezgin, S. Zuhlke, J. G. Hengstler, and D. Drasdo. "In Vitro to in Vivo Acetaminophen Hepatotoxicity Extrapolation Using Classical Schemes, Pharmacodynamic Models and a Multiscale Spatial-Temporal Liver Twin." Front Bioeng Biotechnol 11 (2023): 1049564. https://dx.doi.org/10.3389/fbioe.2023.1049564. 
  1. Gerdemann, A., B. Cramer, G. H. Degen, J. Veerkamp, G. Gunther, W. Albrecht, M. Behrens, M. Esselen, Ghallab, J. G. Hengstler, and H. U. Humpf. "Comparative Metabolism of Aflatoxin B(1) in Mouse, Rat and Human Primary Hepatocytes Using Hplc-Ms/Ms." Archives of Toxicology 97, no. 12 (2023): 3179-96. https://dx.doi.org/10.1007/s00204-023-03607-z.

2022

  1. Ghallab, A., Hassan, U. Hofmann, A. Friebel, Z. Hobloss, L. Brackhagen, B. Begher-Tibbe, M. Myllys, J. Reinders, N. Overbeck, S. Sezgin, S. Zuhlke, A. L. Seddek, W. Murad, T. Brecklinghaus, F. Kappenberg, J. Rahnenfuhrer, D. Gonzalez, C. Goldring, I. M. Copple, R. Marchan, T. Longerich, M. Vucur, T. Luedde, S. Urban, A. Canbay, T. Schreiter, M. Trauner, J. Y. Akakpo, M. Olyaee, S. C. Curry, J. P. Sowa, H. Jaeschke, S. Hoehme, and J. G. Hengstler. "Interruption of Bile Acid Uptake by Hepatocytes after Acetaminophen Overdose Ameliorates Hepatotoxicity." Journal of Hepatology 77, no. 1 (2022): 71-83. https://dx.doi.org/10.1016/j.jhep.2022.01.020. 
  1. Remetic, J., Ghallab, Z. Hobloss, L. Brackhagen, R. Hassan, M. Myllys, R. Radun, V. Mlitz, C. Zhu, M. Baumgartner, W. C. Schrottmaier, M. Mussbacher, G. Timelthaler, H. Scharnagl, T. Stojakovic, A. Assinger, C. D. Fuchs, J. G. Hengstler, and M. Trauner. "Loss of Bile Salt Export Pump Aggravates Lipopolysaccharide-Induced Liver Injury in Mice Due to Impaired Hepatic Endotoxin Clearance." Hepatology 75, no. 5 (2022): 1095-109. https://dx.doi.org/10.1002/he p.32289. 
  1. Hassan, R., A. Friebel, L. Brackhagen, Hobloss, M. Myllys, D. Gonzalez, W. Albrecht, E. S. I. Mohammed, A. L. Seddek, R. Marchan, C. Cadenas, B. Cramer, H. U. Humpf, L. Hartl, B. Simbrunner, T. Reiberger, M. Trauner, S. Hoehme, G. H. Degen, J. G. Hengstler, and A. Ghallab. "Hypoalbuminemia Affects the Spatio-Temporal Tissue Distribution of Ochratoxin a in Liver and Kidneys: Consequences for Organ Toxicity." Archives of Toxicology 96, no. 11 (2022): 2967-81. https://dx.doi.org/10.1007/s00204-022-03361-8. 
  1. Hassan, R., Gonzalez, Z. Hobloss, L. Brackhagen, M. Myllys, A. Friebel, A. L. Seddek, R. Marchan, B. Cramer, H. U. Humpf, S. Hoehme, G. H. Degen, J. G. Hengstler, and A. Ghallab. "Inhibition of Cytochrome P450 Enhances the Nephro- and Hepatotoxicity of Ochratoxin A." Archives of Toxicology 96, no. 12 (2022): 3349-61. https://dx.doi.org/10.1007/s00204-022-03395-y. 
  1. Hassan, R., Myllys, L. Brackhagen, Z. Hobloss, D. Gonzalez, A. L. Seddek, A. Friebel, S. Hoehme, R. Marchan, M. Trauner, J. G. Hengstler, and A. Ghallab. "Colchicine Overdose Impairs the Capacity of Kupffer Cells to Clear Foreign Particles and Endotoxins." Archives of Toxicology 96, no. 11 (2022): 3067-76. https://dx.doi.org/10.1007/s00204-022-03353-8. 
  1. Holland, C. H., R. O. Ramirez Flores, Myllys, R. Hassan, K. Edlund, U. Hofmann, R. Marchan, C. Cadenas, J. Reinders, S. Hoehme, A. L. Seddek, S. Dooley, V. Keitel, P. Godoy, B. Begher-Tibbe, C. Trautwein, C. Rupp, S. Mueller, T. Longerich, J. G. Hengstler, J. Saez-Rodriguez, and A. Ghallab. "Transcriptomic Cross-Species Analysis of Chronic Liver Disease Reveals Consistent Regulation between Humans and Mice." Hepatology Communications 6, no. 1 (2022): 161-77. https://dx.doi.org/10.1002/hep4.1797. 
  1. Wehling, L., L. Keegan, P. Fernandez-Palanca, Hassan, A. Ghallab, J. Schmitt, Y. Tang, M. Le Marois, S. Roessler, P. Schirmacher, U. Kummer, J. G. Hengstler, S. Sahle, and K. Breuhahn. "Spatial Modeling Reveals Nuclear Phosphorylation and Subcellular Shuttling of Yap Upon Drug-Induced Liver Injury." Elife 11 (2022). https://dx.doi.org/10.7554/eLife.78540.
  2. Brecklinghaus, T., W. Albrecht, J. Duda, F. Kappenberg, L. Grundler, K. Edlund, R. Marchan, Ghallab, C. Cadenas, A. Rieck, N. Vartak, L. Tolosa, J. V. Castell, I. Gardner, E. Halilbasic, M. Trauner, A. Ullrich, A. Zeigerer, O. Demirci Turgunbayer, G. Damm, D. Seehofer, J. Rahnenfuhrer, and J. G. Hengstler. "In Vitro/in Silico Prediction of Drug Induced Steatosis in Relation to Oral Doses and Blood Concentrations by the Nile Red Assay." Toxicology Letters 368 (2022): 33-46. https://dx.doi.org/10.1016/j.toxlet.2022.08.006. 
  1. Brecklinghaus, T., W. Albrecht, F. Kappenberg, J. Duda, N. Vartak, K. Edlund, R. Marchan, Ghallab, C. Cadenas, G. Gunther, M. Leist, M. Zhang, I. Gardner, J. Reinders, F. G. Russel, A. J. Foster, D. P. Williams, A. Damle-Vartak, M. Grandits, G. Ecker, N. Kittana, J. Rahnenfuhrer, and J. G. Hengstler. "The Hepatocyte Export Carrier Inhibition Assay Improves the Separation of Hepatotoxic from Non-Hepatotoxic Compounds." Chemico-Biological-Interactions 351 (2022): 109728. https://dx.doi.org/10.1016/j.cbi.2021.109728. 
  1. Brecklinghaus, T., W. Albrecht, F. Kappenberg, J. Duda, M. Zhang, I. Gardner, R. Marchan, Ghallab, O. Demirci Turgunbayer, J. Rahnenfuhrer, and J. G. Hengstler. "Influence of Bile Acids on the Cytotoxicity of Chemicals in Cultivated Human Hepatocytes." Toxicology In Vitro 81 (2022): 105344. https://dx.doi.org/10.1016/j.tiv.2022.105344. 
  1. Budelmann, D., H. Laue, N. Weiss, U. Dahmen, L. A. D'Alessandro, I. Biermayer, U. Klingmuller, Ghallab, R. Hassan, B. Begher-Tibbe, J. G. Hengstler, and L. O. Schwen. "Automated Detection of Portal Fields and Central Veins in Whole-Slide Images of Liver Tissue." Journal of Pathology Informatics 13 (2022): 100001. https://dx.doi.org/10.1016/j.jpi.2022.100001. 
  1. Huang, X., A. K. Nussler, M. K. Reumann, P. Augat, M. M. Menger, Ghallab, J. G. Hengstler, T. Histing, and S. Ehnert. "Contribution to the 3r Principle: Description of a Specimen-Specific Finite Element Model Simulating 3-Point-Bending Tests in Mouse Tibiae." Bioengineering (Basel) 9, no. 8 (2022). https://dx.doi.org/10.3390/bioengineering9080337. 
  1. Kube, I., M. Kowalczyk, U. Hofmann, Ghallab, J. G. Hengstler, D. Fuhrer, and D. Zwanziger. "Hepatobiliary Thyroid Hormone Deficiency Impacts Bile Acid Hydrophilicity and Aquaporins in Cholestatic C57bl/6j Mice." International Journal of Molecular Sciences 23, no. 20 (2022). https://dx.doi.org/10.3390/ijms232012355. 
  1. Mohammed, E. S. I., F. A. Madkour, M. Zayed, R. Radey, Ghallab, and R. Hassan. "Comparative Histological Analysis of the Skin for Forensic Investigation of Some Animal Species." EXCLI J 21 (2022): 1286-98. https://dx.doi.org/10.17179/excli2022-5335. 
  1. Schnabl, B., G. E. Arteel, F. Stickel, J. Hengstler, N. Vartak, Ghallab, S. Dooley, Y. Li, and R. F. Schwabe. "Liver Specific, Systemic and Genetic Contributors to Alcohol-Related Liver Disease Progression." Zeitschrift für Gastroenterologie 60, no. 1 (2022): 36-44. https://dx.doi.org/10.1055/a-1714-9330.

2021

  1. Schneider, K. M., L. S. Candels, J. R. Hov, Myllys, R. Hassan, C. V. Schneider, A. Wahlstrom, A. Mohs, S. Zuhlke, L. Liao, C. Elfers, K. Kilic, M. Henricsson, A. Molinaro, M. Hatting, A. Zaza, D. Drasdo, M. Frissen, A. S. Devlin, E. J. C. Galvez, T. Strowig, T. H. Karlsen, J. G. Hengstler, H. U. Marschall, A. Ghallab, and C. Trautwein. "Gut Microbiota Depletion Exacerbates Cholestatic Liver Injury Via Loss of Fxr Signalling." Nature Metabolism 3, no. 9 (2021): 1228-41. https://dx.doi.org/10.1038/s42255-021-00452-1. 
  1. Ghallab, A., Hassan, M. Myllys, W. Albrecht, A. Friebel, S. Hoehme, U. Hofmann, A. L. Seddek, A. Braeuning, L. Kuepfer, B. Cramer, H. U. Humpf, P. Boor, G. H. Degen, and J. G. Hengstler. "Subcellular Spatio-Temporal Intravital Kinetics of Aflatoxin B(1) and Ochratoxin a in Liver and Kidney." Archives of Toxicology 95, no. 6 (2021): 2163-77. https://dx.doi.org/10.1007/s00204-021-03073-5. 
  1. Ghallab, A., Myllys, A. Friebel, J. Duda, K. Edlund, E. Halilbasic, M. Vucur, Z. Hobloss, L. Brackhagen, B. Begher-Tibbe, R. Hassan, M. Burke, E. Genc, L. J. Frohwein, U. Hofmann, C. H. Holland, D. Gonzalez, M. Keller, A. L. Seddek, T. Abbas, E. S. I. Mohammed, A. Teufel, T. Itzel, S. Metzler, R. Marchan, C. Cadenas, C. Watzl, M. A. Nitsche, F. Kappenberg, T. Luedde, T. Longerich, J. Rahnenfuhrer, S. Hoehme, M. Trauner, and J. G. Hengstler. "Spatio-Temporal Multiscale Analysis of Western Diet-Fed Mice Reveals a Translationally Relevant Sequence of Events During Nafld Progression." Cells 10, no. 10 (2021). https://dx.doi.org/10.3390/cells10102516. 
  1. Gianmoena, K., N. Gasparoni, A. Jashari, P. Gabrys, K. Grgas, Ghallab, K. Nordstrom, G. Gasparoni, J. Reinders, K. Edlund, P. Godoy, A. Schriewer, H. Hayen, C. A. Hudert, G. Damm, D. Seehofer, T. S. Weiss, P. Boor, H. J. Anders, M. Motrapu, P. Jansen, T. S. Schiergens, M. Falk-Paulsen, P. Rosenstiel, C. Lisowski, E. Salido, R. Marchan, J. Walter, J. G. Hengstler, and C. Cadenas. "Epigenomic and Transcriptional Profiling Identifies Impaired Glyoxylate Detoxification in Nafld as a Risk Factor for Hyperoxaluria." Cell Reports 36, no. 8 (2021): 109526. https://dx.doi.org/10.1016/j.celrep.2021.109526. 
  1. Gupta, R., Y. Schrooders, D. Hauser, M. van Herwijnen, W. Albrecht, B. Ter Braak, T. Brecklinghaus, J. V. Castell, L. Elenschneider, S. Escher, P. Guye, J. G. Hengstler, Ghallab, T. Hansen, M. Leist, R. Maclennan, W. Moritz, L. Tolosa, T. Tricot, C. Verfaillie, P. Walker, B. van de Water, J. Kleinjans, and F. Caiment. "Comparing in Vitro Human Liver Models to in Vivo Human Liver Using Rna-Seq." Archives of Toxicology 95, no. 2 (2021): 573-89. https://dx.doi.org/10.1007/s00204-020-02937-6. 
  1. Koeppert, S., Ghallab, S. Peglow, C. F. Winkler, S. Graeber, A. Buscher, J. G. Hengstler, and W. Jahnen-Dechent. "Live Imaging of Calciprotein Particle Clearance and Receptor Mediated Uptake: Role of Calciprotein Monomers." Frontiers in Cell and Developmental Biology 9 (2021): 633925. https://dx.doi.org/10.3389/fcell.2021.633925. 
  1. Kube, I., L. B. Tardio, U. Hofmann, Ghallab, J. G. Hengstler, D. Fuhrer, and D. Zwanziger. "Hypothyroidism Increases Cholesterol Gallstone Prevalence in Mice by Elevated Hydrophobicity of Primary Bile Acids." Thyroid 31, no. 6 (2021): 973-84. https://dx.doi.org/10.1089/thy.2020.0636. 
  1. Schneider, K. M., C. Elfers, Ghallab, C. V. Schneider, E. J. C. Galvez, A. Mohs, W. Gui, L. S. Candels, T. H. Wirtz, S. Zuehlke, M. Spiteller, M. Myllys, A. Roulet, A. Ouzerdine, B. Lelouvier, K. Kilic, L. Liao, A. Nier, E. Latz, I. Bergheim, C. A. Thaiss, J. G. Hengstler, T. Strowig, and C. Trautwein. "Intestinal Dysbiosis Amplifies Acetaminophen-Induced Acute Liver Injury." Cellular and Molecular Gastroenterololgy and Hepatology 11, no. 4 (2021): 909-33. https://dx.doi.org/10.1016/j.jcmgh.2020.11.002. 
  1. Schuran, F. A., C. Lommetz, A. Steudter, Ghallab, B. Wieschendorf, D. Schwinge, S. Zuehlke, J. Reinders, J. Heeren, A. W. Lohse, C. Schramm, J. Herkel, and A. Carambia. "Aryl Hydrocarbon Receptor Activity in Hepatocytes Sensitizes to Hyperacute Acetaminophen-Induced Hepatotoxicity in Mice." Cellular and Molecular Gastroenterololgy and Hepatology 11, no. 2 (2021): 371-88. https://dx.doi.org/10.1016/j.jcmgh.2020.09.002. 
  1. Vartak, N., G. Guenther, F. Joly, A. Damle-Vartak, G. Wibbelt, J. Fickel, S. Jors, B. Begher-Tibbe, A. Friebel, K. Wansing, Ghallab, M. Rosselin, N. Boissier, I. Vignon-Clementel, C. Hedberg, F. Geisler, H. Hofer, P. Jansen, S. Hoehme, D. Drasdo, and J. G. Hengstler. "Intravital Dynamic and Correlative Imaging of Mouse Livers Reveals Diffusion-Dominated Canalicular and Flow-Augmented Ductular Bile Flux." Hepatology 73, no. 4 (2021): 1531-50. https://dx.doi.org/10.1002/hep.31422.

2020

  1. Campos, G., W. Schmidt-Heck, J. De Smedt, A. Widera, Ghallab, L. Putter, D. Gonzalez, K. Edlund, C. Cadenas, R. Marchan, R. Guthke, C. Verfaillie, C. Hetz, A. Sachinidis, A. Braeuning, M. Schwarz, T. S. Weiss, B. K. Banhart, J. Hoek, R. Vadigepalli, J. Willy, J. L. Stevens, D. C. Hay, J. G. Hengstler, and P. Godoy. "Inflammation-Associated Suppression of Metabolic Gene Networks in Acute and Chronic Liver Disease." Archives of Toxicology 94, no. 1 (2020): 205-17. https://dx.doi.org/10.1007/s00204-019-02630-3.

2019

  1. Ghallab, A., U. Hofmann, S. Sezgin, N. Vartak, Hassan, A. Zaza, P. Godoy, K. M. Schneider, G. Guenther, Y. A. Ahmed, A. A. Abbas, V. Keitel, L. Kuepfer, S. Dooley, F. Lammert, C. Trautwein, M. Spiteller, D. Drasdo, A. F. Hofmann, P. L. M. Jansen, J. G. Hengstler, and R. Reif. "Bile Microinfarcts in Cholestasis Are Initiated by Rupture of the Apical Hepatocyte Membrane and Cause Shunting of Bile to Sinusoidal Blood." Hepatology 69, no. 2 (2019): 666-83. https://dx.doi.org/10.1002/hep.30213. 
  1. Ghallab, A., Myllys, C. H. Holland, A. Zaza, W. Murad, R. Hassan, Y. A. Ahmed, T. Abbas, E. A. Abdelrahim, K. M. Schneider, M. Matz-Soja, J. Reinders, R. Gebhardt, M. L. Berres, M. Hatting, D. Drasdo, J. Saez-Rodriguez, C. Trautwein, and J. G. Hengstler. "Influence of Liver Fibrosis on Lobular Zonation." Cells 8, no. 12 (2019). https://dx.doi.org/10.3390/cells8121556.
  2. Albrecht, W., F. Kappenberg, T. Brecklinghaus, R. Stoeber, R. Marchan, M. Zhang, K. Ebbert, H. Kirschner, M. Grinberg, M. Leist, W. Moritz, C. Cadenas, Ghallab, J. Reinders, N. Vartak, C. van Thriel, K. Golka, L. Tolosa, J. V. Castell, G. Damm, D. Seehofer, A. Lampen, A. Braeuning, T. Buhrke, A. C. Behr, A. Oberemm, X. Gu, N. Kittana, B. van de Water, R. Kreiling, S. Fayyaz, L. van Aerts, B. Smedsrod, H. Ellinger-Ziegelbauer, T. Steger-Hartmann, U. Gundert-Remy, A. Zeigerer, A. Ullrich, D. Runge, S. M. L. Lee, T. S. Schiergens, L. Kuepfer, A. Aguayo-Orozco, A. Sachinidis, K. Edlund, I. Gardner, J. Rahnenfuhrer, and J. G. Hengstler. "Prediction of Human Drug-Induced Liver Injury (Dili) in Relation to Oral Doses and Blood Concentrations." Archives of Toxicology 93, no. 6 (2019): 1609-37. https://dx.doi.org/10.1007/s00204-019-02492-9.

2018

  1. Köppert, S., Büscher, A., Babler, A., Ghallab, A., Buhl, E.M., Latz, E., Hengstler, J.G., Smith, E.R., Jahnen-Dechent, W. "Cellular Clearance and Biological Activity of Calciprotein Particles Depend on Their Maturation State and Crystallinity." Frontiers in Immunology 9 (2018): 1991. https://doi.org/10.3389/fimmu.2018.01991.
  2. Ahmed, Y. A., Ali, S., & Ghallab, A. "Hair histology as a tool for forensic identification of some domestic animal species." EXCLI journal 17, (2018): 663–670. https://doi.org/10.17179/excli2018-1478.
  3. Sezgin, S., Hassan, R., Zühlke, S., Kuepfer, L., Hengstler, J. G., Spiteller, M., & Ghallab, A. "Spatio-temporal visualization of the distribution of acetaminophen as well as its metabolites and adducts in mouse livers by MALDI MSI." Archives of Toxicology92, no. 9 (2018): 2963–2977. https://doi.org/10.1007/s00204-018-2271-3.

2017

  1. Jansen, P. L., Ghallab, A., Vartak, N., Reif, R., Schaap, F. G., Hampe, J., & Hengstler, J. G. "The ascending pathophysiology of cholestatic liver disease." Hepatology65, no. 2 (2017): 722–738. https://doi.org/10.1002/hep.28965.
  2. Leist, M., Ghallab, A., Graepel, R., Marchan, R., Hassan, R., Bennekou, S. H., Limonciel, A., Vinken, M., Schildknecht, S., Waldmann, T., Danen, E., van Ravenzwaay, B., Kamp, H., Gardner, I., Godoy, P., Bois, F. Y., Braeuning, A., Reif, R., Oesch, F., Drasdo, D., Hoehme, S., Schwarz, M., Hartung, M., Braunbeck, T., Beltman, J., Vrieling, H., Sanz, F., Forsby, A., Gadaleta, D., Fisher, C., Kelm, J., Fluri, D., Ecker, G., Zdrazil, B., Terron, A., Jennings, P., van der Burg, B., Dooley, S., Meijer, A.H., Willighagen, E., Martens, M., Evelo, C., Mombelli, E., Taboureau, O., Mantovani, A., Hardy, B., Koch, B., Escher, S., van Thriel, C., Cadenas, C., Kroese, D., van de Water, B., Hengstler, J. G. "Adverse outcome pathways: opportunities, limitations and open questions." Archives of Toxicology91 11 (2017): 3477–3505. https://doi.org/10.1007/s00204-017-2045-3.
  3. Reif, R., Ghallab, A., Beattie, L., Günther, G., Kuepfer, L., Kaye, P. M., & Hengstler, J. G. "In vivo imaging of systemic transport and elimination of xenobiotics and endogenous molecules in mice." Archives of Toxicology91 no. 3 (2017): 1335–1352. https://doi.org/10.1007/s00204-016-1906-5.
  4. Schenk, A., Ghallab, A., Hofmann, U., Hassan, R., Schwarz, M., Schuppert, A., Schwen, L. O., Braeuning, A., Teutonico, D., Hengstler, J. G., & Kuepfer, L. "Physiologically-based modelling in mice suggests an aggravated loss of clearance capacity after toxic liver damage." Scientific reports7 no. 1 (2017): https://doi.org/10.1038/s41598-017-04574-z.

2016

  1. Reif, R., Adawy, A., Vartak, N., Schröder, J., Günther, G., Ghallab, A., Schmidt, M., Schormann, W., & Hengstler, J. G. "Activated ErbB3 Translocates to the Nucleus via Clathrin-independent Endocytosis, Which Is Associated with Proliferating Cells." The Journal of biological chemistry291 no. 8 (2016): 3837–3847. https://doi.org/10.1074/jbc.M115.686782.
  2. 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, W. E., Damm, G., Seehofer, D., Weiss, T. S., Dirsch, O., Dahmen, U., Gebhardt, R., Chaudhari, U., Meganathan, K., Sachinidis, A., Kelm, J., Hofmann, U., Zahedi, R.P., Guthke, R., Blüthgen, N., Dooley, S., Hengstler, J. G. "Gene network activity in cultivated primary hepatocytes is highly similar to diseased mammalian liver tissue." Archives of Toxicology, 90 no. 10 (2016): 2513–2529. https://doi.org/10.1007/s00204-016-1761-4.
  3. Ghallab, A., Cellière, G., Henkel, S. G., 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, J. G. "Model-guided identification of a therapeutic strategy to reduce hyperammonemia in liver diseases." Journal of Hepatology 64, no. 4 (2016): 860–871. https://doi.org/10.1016/j.jhep.2015.11.018.

2015

  1. Bartl, M., Pfaff, M., Ghallab, A., Driesch, D., Henkel, S. G., Hengstler, J. G., Schuster, S., Kaleta, C., Gebhardt, R., Zellmer, S., & Li, P. "Optimality in the zonation of ammonia detoxification in rodent liver." Archives of Toxicology, 89 no. 11 (2015): 2069–2078. https://doi.org/10.1007/s00204-015-1596-4.
  2. Thiel, C., Schneckener, S., Krauss, M., Ghallab, A., Hofmann, U., Kanacher, T., Zellmer, S., Gebhardt, R., Hengstler, J. G., & Kuepfer, L. "A systematic evaluation of the use of physiologically based pharmacokinetic modeling for cross-species extrapolation." Journal of Pharmaceutical Sciences, 104 no. 1 (2015): 191–206. https://doi.org/10.1002/jps.24214.

2014

  1. Drasdo, D., Bode, J., Dahmen, U., Dirsch, O., Dooley, S., Gebhardt, R., Ghallab, A., Godoy, P., Häussinger, D., Hammad, S., Hoehme, S., Holzhütter, H. G., Klingmüller, U., Kuepfer, L., Timmer, J., Zerial, M., & Hengstler, J. G. "The virtual liver: state of the art and future perspectives." Archives of Toxicology, 88 no. 12 (2014): 2071–2075. https://doi.org/10.1007/s00204-014-1384-6.
  2. Schliess, F.*, Hoehme, S.*, Henkel, S. G.*, Ghallab, A.*, Driesch, D., Böttger, J., Guthke, R., Pfaff, M., Hengstler, J. G., Gebhardt, R., Häussinger, D., Drasdo, D., & Zellmer, S. "Integrated metabolic spatial-temporal model for the prediction of ammonia detoxification during liver damage and regeneration." Hepatology 60 no. 6 (2014): 2040–2051. https://doi.org/10.1002/hep.27136.* equal contributions.
  3. Campos, G., Schmidt-Heck, W., Ghallab, A., Rochlitz, K., Pütter, L., Medinas, D. B., Hetz, C., Widera, A., Cadenas, C., Begher-Tibbe, B., Reif, R., Günther, G., Sachinidis, A., Hengstler, J. G., & Godoy, P. "The transcription factor CHOP, a central component of the transcriptional regulatory network induced upon CCl4 intoxication in mouse liver, is not a critical mediator of hepatotoxicity." Archives of Toxicology 88 no. 6 (2014): 1267–1280. https://doi.org/10.1007/s00204-014-1240-8.