{"id":668,"date":"2019-12-04T08:19:04","date_gmt":"2019-12-04T08:19:04","guid":{"rendered":"http:\/\/new.svu.edu.eg\/faculties\/vet\/?post_type=departments&p=668"},"modified":"2020-01-29T10:04:21","modified_gmt":"2020-01-29T10:04:21","slug":"%d8%a7%d9%86%d8%b4%d8%b7%d8%a9-%d8%b9%d9%84%d9%85%d9%8a%d8%a9-%d9%84%d9%82%d8%b3%d9%85-%d8%a7%d9%84%d8%b7%d8%a8-%d8%a7%d9%84%d8%b4%d8%b1%d8%b9%d9%89-%d9%88%d8%a7%d9%84%d8%b3%d9%85%d9%88%d9%85","status":"publish","type":"departments","link":"https:\/\/www.svu.edu.eg\/faculties\/vet\/departments\/%d9%82%d8%b3%d9%85-%d8%a7%d9%84%d8%b7%d8%a8-%d8%a7%d9%84%d8%b4%d8%b1%d8%b9%d9%8a-%d9%88-%d8%a7%d9%84%d8%b3%d9%85%d9%88%d9%85\/%d8%a7%d9%86%d8%b4%d8%b7%d8%a9-%d8%b9%d9%84%d9%85%d9%8a%d8%a9-%d9%84%d9%82%d8%b3%d9%85-%d8%a7%d9%84%d8%b7%d8%a8-%d8%a7%d9%84%d8%b4%d8%b1%d8%b9%d9%89-%d9%88%d8%a7%d9%84%d8%b3%d9%85%d9%88%d9%85\/","title":{"rendered":"\u0627\u0646\u0634\u0637\u0629 \u0639\u0644\u0645\u064a\u0629 \u0644\u0642\u0633\u0645 \u0627\u0644\u0637\u0628 \u0627\u0644\u0634\u0631\u0639\u0649 \u0648\u0627\u0644\u0633\u0645\u0648\u0645"},"content":{"rendered":"\n


Running projects and publications of Dr. Ahmed Ghallab<\/strong><\/a>
<\/strong><\/p>\n\n\n\n

Functional intravital imaging of the liver<\/strong><\/p>\n\n\n\n

Two-photon microscopy enables imaging of biological processes <\/strong>in vivo<\/strong><\/em> in real time. Videos can be taken at subcellular resolution but also the imaging of overviews over several lobules is possible. Establishing this technique in mouse liver allowed us to get insights into the sequence of events during liver damage and regeneration which are difficult to obtain with the conventional techniques.<\/strong><\/p>\n\n\n\n

Videos  legends<\/strong>
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Video 1: Liver morphology visualized by administration of a mitochondrial membrane potential marker. Mitochondria of hepatocytes and a Kupffer cell (arrow) in a wildtype mouse following uptake of Rhodamine 123<\/strong> Video<\/a><\/strong> <\/a>
<\/a><\/strong><\/p>\n\n\n\n

Video 2: LSEC in a Tie2 x mT\/mG reporter mouse. The arrow indicates the nucleus of a LSEC. Moreover, platelets and some immune cells also express eGFP.<\/strong> Video<\/a><\/strong>
<\/a><\/strong><\/p>\n\n\n\n

Video 3: Kupffer cells expressing eGFP in a LysM x mT\/mG reporter mouse.<\/strong> Video<\/a> <\/strong> <\/p>\n\n\n\n

Video 4: Hepatic transport of CLF. Wildtype mouse pre-injected with TMRE (red) was imaged after tail vein injection of CLF (2.5 mg\/kg). <\/strong> Video<\/a><\/strong> <\/p>\n\n\n\n

Video 5: Neutrophils swarming after physical liver damage. A LysM x mT\/mG mouse was treated with high energy laser at the indicated region (circle) 6<\/strong> minutes into the imaging window and infiltrating neutrophils (green) were imaged.<\/strong> Video<\/a><\/strong> <\/strong><\/p>\n\n\n\n

Video 6: Transport of cholyl-lysyl-fluorescin (CLF) in a cholestatic liver. A bile duct-ligated mouse (day 3) pre-injected with Hoechst 33258 (5 mg\/kg, red) was imaged after a tail vein injection of CLF (1 mg\/kg, green).video
<\/a><\/strong><\/p>\n\n\n\n

Model-guided pharmacotherapy in chronic liver disease<\/strong><\/p>\n\n\n\n

A common cause of death of patients with advanced chronic liver disease is acute – on -chronic liver failure (ACLF). Because of the complexity of the responsible mechanisms, ACLF remains difficult to predict. In our previous work we have established modeling techniques which have the potential to improve the situation (Ghallab et al, Hepatology, 2014). These models allow the simulation of the relationship between compromised hepatic metabolism, specific spatio-temporal damage patterns of critical liver functions and their relationship to different forms of liver failure. In the present project we will extend the integrated spatio-temporal\/metabolic models established in the virtual liver network (VLN) to guide pharmacotherapy in chronic liver disease and to avoid application of drug doses that will lead to ACLF. A particular strength of our integrated models is that they allow identification of specific therapeutic interventions in chronic liver disease. A typical complication in chronic liver disease is compromised ammonia metabolism. Our spatio-temporal\/metabolic model predicted a specific intervention in chronic liver disease that, given its successful translation to patients, will provide a realistic alternative to aggressive therapies, such as hemodialysis, for those diagnosed with severe hyperammonemia due to chronic liver disease. In conclusion, the proposed project will deliver (i) integrated PBPK\/spatio-temporal models that guide pharmacotherapy in chronic liver disease to avoid drug induced acute on chronic liver failure, (ii) guide pharmacotherapy of chronic liver disease to interfere with disturbed metabolic networks of ammonia metabolism to ameliorate hyperammonemia<\/strong><\/p>\n\n\n\n

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Iterative cycles of modelling and experimental validation
<\/strong><\/p>\n\n\n\n

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Spatio-temporal modelling of ammonia detoxification during liver damage and regeneration on the level of the individual cell\u00a0(A-F). The three frontal left lobules show the destruction and the regeneration process following CCl<\/strong>4<\/strong><\/sub>\u00a0intoxication. The red colored shade indicates hepatocytes proliferation. The other four liver lobules show the alteration of ammonia metabolism during liver damage and regeneration on each individual hepatocyte. The highest concentration of ammonia is in the periportal region (red color), whereas minimal ammonia concentration is in the pericentral region (blue color). Time points where images were taken are (T= 0, 12h, 1d, 2d, 4d and 6d days after injection of 1.6 g\/kg CCl<\/strong>4<\/strong><\/sub>).
<\/strong><\/p>\n\n\n\n

Spatio-temporal modelling of ammonia detoxification during liver damage and regeneration on the level of the individual cell<\/strong>
<\/p>\n\n\n\n

Role of non-parenchymal cells in liver regeneration<\/strong><\/p>\n\n\n\n

Although acetaminophen (APAP) induced liver injury is extensively studied, the contribution of the non-parenchymal cells as well as the infiltrating immune cells to the destruction and the regeneration processes is still under investigation. The purpose of this project is to investigate the impact of acetaminophen overdose on various liver cell types with a specific focus on the control of hepatic stellate cells dynamic during liver injury and regeneration processes. The main objectives are to<\/strong><\/p>\n\n\n\n

\u00b7\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0study liver injury and regeneration following APAP intoxication.<\/strong><\/p>\n\n\n\n

\u00b7\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0identify the liver resident as well as infiltrating immune cells during liver injury and regeneration following APAP overdose.<\/strong><\/p>\n\n\n\n

\u00b7\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0study the activation of HSCs following liver injury and their fate during recovery.<\/strong><\/p>\n\n\n\n

\u00b7\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0investigate the impact of macrophages depletion on HSCs clearance during liver regeneration.<\/strong><\/p>\n\n\n\n

\u00b7\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0identify the possible backup mechanisms that protect against liver fibrosis after macrophages removal.
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Hepatic stellate cells (HSCs) dynamics after liver injury.\u00a0Following liver injury HSCs transdifferentiate into myofibroblasts-like cells and migrate to the site of injury where they produce extracellular matrix leading to liver fibrosis. However, depending on the duration of injury, this process can be reversible. After cessation of liver injury activated HSCs disappear by apoptosis or by reversion to a quiescent phenotype.
<\/strong><\/p>\n\n\n\n

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Major cell types which interact with HSCs during fibrogenesis and fibrosis regression.<\/strong><\/p>\n\n\n\n

Selected Publications<\/strong><\/p>\n\n\n\n

Peer reviewed journal<\/em><\/strong><\/p>\n\n\n\n

Ghallab A,<\/strong> S.G. Henkel, G. Celli\u00e8re, D. Driesch, S. Hoehme, U. Hofmann, S. Zellmer, P. Godoy, A. Sachinidis, M. Blaszkewicz, R. Reif, R. Marchan, L. Kuepfer, D. H\u00e4ussinger, D. Drasdo, R. Gebhardt, J.G. Hengstler “Model guided identification and therapeutic implications of an ammonia sink mechanism.” Journal of Hepatology<\/em><\/strong>, 64, no.4 (2016): 860:871. (impact factor: 10.59).<\/em><\/strong><\/p>\n\n\n\n

Ghallab A*<\/strong>, <\/strong>F. Schliess*., S. Hoehme*, S. G. Henkel*, <\/strong> D. Driesch, J. Bottger, R. Guthke, M. Pfaff, J. G. Hengstler, R. Gebhardt, D. Haussinger, D. Drasdo and S. Zellmer. “Integrated Metabolic Spatial-Temporal Model for the Prediction of Ammonia Detoxification During Liver Damage and Regeneration.” Hepatology<\/em><\/strong> <\/em><\/strong>60, no.6  (2014):2040-2051.*indicates equal contribution. (impact factor: 11.711).<\/em><\/strong>
<\/p>\n\n\n\n

Ghallab A<\/a>*<\/strong>, <\/strong>M. Bartl<\/a>*, M. Pfaff<\/a>*, D. Driesch<\/a>, S.G. Henkel<\/a>, J.G. Hengstler<\/a>, S. Schuster<\/a>, C. Kaleta<\/a>, R. Gebhardt<\/a>, S. Zellmer<\/a>, P. Li<\/a>. “Optimality in the zonation of ammonia detoxification in rodent liver. ” Arch Toxicol<\/em><\/strong> 89, no.11 (2015): 2069-2078. *indicates equal contribution. (impact factor: 6.637).<\/em><\/strong>
<\/p>\n\n\n\n

Jansen PLM, A. Ghallab<\/strong>, N. Vartak, R. Reif, FG. Scaap, J. Hampe and J. G. Hengstler. ” The ascending pathophysiology of cholestatic liver disease.” Hepatology<\/em><\/strong> (2016), Accepted. (impact factor: 11.711).<\/em><\/strong>
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Ghallab A<\/a>*, <\/strong>R. Reif*, <\/strong>L. Beattie<\/a>, G. Guenther, L. Kuepfer, PM. Kaye and J.G. Hengstler<\/a> “In vivo imaging of systemic transport and elimination of xenobiotics and endogenous molecules in mice.\u201d Arch Toxicol<\/em><\/strong> (2016), Accepted. *indicates equal contribution. (impact factor: 6.637).<\/em><\/strong>
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 Campos G, W. Schmidt-Heck, A. Ghallab<\/strong>, K. Rochlitz, L. Putter, D. B. Medinas, C. Hetz, A. Widera, C. Cadenas, B. Begher-Tibbe, R. Reif, G. Gunther, A. Sachinidis, J. G. Hengstler and P. Godoy. “The Transcription Factor Chop, a Central Component of the Transcriptional Regulatory Network Induced Upon CCl4<\/sub> Intoxication in Mouse Liver, Is Not a Critical Mediator of Hepatotoxicity.” Arch Toxicol<\/em><\/strong> 88, no. 6 (2014): 1267-1280. (impact factor: 6.637).<\/em><\/strong>
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Thiel C, S. Schneckener, M. Krauss, A. Ghallab<\/strong>, U. Hofmann, T. Kanacher, S. Zellmer, R. Gebhardt, JG. Hengstler and L. Kuepfer. \u201cA Systematic  Evaluation  of  the  Use  of  Physiologically-Based Pharmacokinetic Modeling for Cross-Species Extrapolation\u201d. Journal of Pharmaceutical Sciences<\/strong><\/em> 104, no. 1 (2015): 191-206 (impact factor: 3.007).<\/em><\/strong>
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Godoy P, A. Widera,\u2026. A. Ghallab<\/strong>, \u2026. and J. G. Hengstler. ” Gene network activity in cultivated primary hepatocytes is highly similar to diseased mammalian liver tissue.” Arch Toxicol<\/em><\/strong> 90, no. 10 (2016): 2513-2529. (impact factor: 6.637).<\/em><\/strong>
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 ADDIN EN.REFLIST Heise T, M. Schug, D. Storm, H. Ellinger-Ziegelbauer, H. J. Ahr, B. Hellwig, J. Rahnenfuhrer, A. Ghallab<\/strong>, G. Guenther, J. Sisnaiske, R. Reif, P. Godoy, H. Mielke, U. Gundert-Remy, A. Lampen, A. Oberemm and J. G. Hengstler. “In Vitro – in Vivo Correlation of Gene Expression Alterations Induced by Liver Carcinogens.” Curr Med Chem<\/em><\/strong> 19, no. 11 (2012): 1721-1730. (impact factor: 3.455).<\/em><\/strong>
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Ghallab A<\/strong>,”Blueprint for stem cell differentiation into liver cells”. EXCLI Journal<\/em><\/strong> 14 (2015): 1       017-1019. (impact factor: 1.292).<\/em><\/strong>
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Ghallab A<\/strong>, “Acetaminophen hepatotoxicity.” Arch Toxicol<\/em><\/strong> 89, no. 12 (2015): 2449-2451. (impact factor: 6.637).<\/em><\/strong>
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Ghallab A<\/strong>, “Role of the circadian clock system in breast cancer”. EXCLI Journal <\/em><\/strong>14 (2015): 540-541. (impact factor: 1.292).<\/em><\/strong>
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Ghallab A<\/strong>, “Perspectives in stem cell research\u2014unbiased quantification of the similarity between in vitro generated and primary hepatocytes.” Arch Toxicol<\/em><\/strong> 89, no. 11 (2015): 2185-2187. (impact factor: 6.637).<\/em><\/strong>
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Ghallab  A<\/strong>, “In vitro test systems and their limitations”.  EXCLI Journal <\/em><\/strong>12 (2013): 1024-1026 (impact factor: 1.292).<\/em><\/strong>
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 Ghallab<\/strong> A<\/strong>, <\/strong>“Perspectives in Toxicologic Pathology: Quantification of Bile Canalicular Networks.” Arch Toxicol<\/em><\/strong> 88, no. 10 (2014): 1907-1908. (impact factor: 6.637).<\/em><\/strong>
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Drasdo D, J. Bode, U. Dahmen, O. Dirsch, S. Dooley, R. Gebhardt, A. Ghallab<\/strong>, P. Godoy, D. Haussinger, S. Hammad, S. Hoehme, H. G. Holzhutter, U. Klingmuller, L. Kuepfer, J. Timmer, M. Zerial and J. G. Hengstler. “The Virtual Liver: State of the Art and Future Perspectives.” Arch Toxicol<\/em><\/strong> 88, no. 12 (2014): 2071-5. (impact factor: 6.637).<\/em><\/strong>
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Ghallab A<\/strong>, and H. M. Bolt. “In Vitro Systems: Current Limitations and Future Perspectives.”Arch Toxicol<\/em><\/strong> 88, no. 12 (2014): 2085-2087. (impact factor: 6.637).<\/em><\/strong>
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Ghallab A<\/strong>, <\/strong>\u201cHighlights in tumor metabolome research: choline metabolism influences integrin expression and supports cell attachment\u201d. EXCLI Journal <\/em><\/strong>13<\/em>, (2014):856-858. (impact factor: 1.292).<\/em><\/strong>
<\/p>\n\n\n\n

Ghallab A<\/strong>, \u201cHuman Non-Parenchymal Liver Cells For Co-Cultivation Systems.\u201d EXCLI Journal<\/em><\/strong> 13 (2014):1295-1296. (impact factor: 1.292).<\/em><\/strong>
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Ghallab A<\/strong>, \u201cSystems toxicology.\u201d EXCLI Journal<\/em><\/strong> 14 (2015):1261-1263. (impact factor: 1.292).<\/em><\/strong>
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Ghallab A<\/strong>, \u201cNew methods for quantification of bile canalicular dynamics.\u201d EXCLI Journal<\/em><\/strong> 14 (2015):1264-1266. (impact factor: 1.292).<\/em><\/strong>
<\/p>\n\n\n\n

Ghallab A<\/strong>, \u201cInterspecies extrapolation by phsyologically based pharmacokinetic modelling.\u201d EXCLI Journal<\/em><\/strong> 14 (2015):1267-1269. (impact factor: 1.292).<\/em><\/strong>
<\/p>\n\n\n\n

Ghallab, A.<\/strong> \u201cThe Rediscovery of HEPG2 Cells for Prediction Of Drug Induced Liver Injury (DILI).\u201d EXCLI Journal<\/em><\/strong> 13 (2014):1286-1288. (impact factor: 1.292).<\/em><\/strong>
<\/p>\n\n\n\n

Reif R, A. Adawy, N. Vartak, J. Schroeder, G. Guenther, A. Ghallab<\/strong>, W. Schormann, M. Schmidt, J. G. Hengstler. \u201cActivated ErbB3 translocates to the nucleus via clathrin-independent endocytosis in proliferating cells. \u201d The Journal of Biological Chemistry<\/em><\/strong>  291, no. 8 (2015): 3837-3847. (impact factor: 4.258).<\/em><\/strong>
<\/p>\n\n\n\n

Book contribution<\/em><\/strong><\/p>\n\n\n\n

Hengstler, JG, S. Hammad, A. Ghallab<\/strong>, R. Reif and P. Godoy. \u201cIn Vitro Systems for Hepatotoxicity Testing\u201d. Anna Bal-Price, Paul Jennings (eds). In Vitro Toxicology Systems<\/em><\/strong>, Methods in Pharmacology and Toxicology, DOI 10.1007\/978-1-4939-0521-8_2, (2014): 27-44.<\/p>\n\n\n\n

Scenck A, A. Ghallab<\/strong>, U. Hofmann, R. Hassan\u2026.. and L. Kuepfer.”Physiologically-based modelling  in  mice  suggests  an  aggravated  loss  of  clearance  capacity after toxic liver damage.” Scientific Reports<\/em><\/strong> (2016), in revision. (impact factor: 5.228).<\/em><\/strong>
<\/p>\n","protected":false},"excerpt":{"rendered":"

Running projects and publications of Dr. Ahmed Ghallab Functional intravital imaging of the liver Two-photon microscopy enables imaging of biological processes in vivo in real time. Videos can be taken at subcellular […]<\/p>\n","protected":false},"author":2,"featured_media":0,"parent":660,"menu_order":0,"comment_status":"open","ping_status":"open","template":"","format":"standard","_links":{"self":[{"href":"https:\/\/www.svu.edu.eg\/faculties\/vet\/wp-json\/wp\/v2\/departments\/668"}],"collection":[{"href":"https:\/\/www.svu.edu.eg\/faculties\/vet\/wp-json\/wp\/v2\/departments"}],"about":[{"href":"https:\/\/www.svu.edu.eg\/faculties\/vet\/wp-json\/wp\/v2\/types\/departments"}],"author":[{"embeddable":true,"href":"https:\/\/www.svu.edu.eg\/faculties\/vet\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.svu.edu.eg\/faculties\/vet\/wp-json\/wp\/v2\/comments?post=668"}],"version-history":[{"count":10,"href":"https:\/\/www.svu.edu.eg\/faculties\/vet\/wp-json\/wp\/v2\/departments\/668\/revisions"}],"predecessor-version":[{"id":2631,"href":"https:\/\/www.svu.edu.eg\/faculties\/vet\/wp-json\/wp\/v2\/departments\/668\/revisions\/2631"}],"up":[{"embeddable":true,"href":"https:\/\/www.svu.edu.eg\/faculties\/vet\/wp-json\/wp\/v2\/departments\/660"}],"wp:attachment":[{"href":"https:\/\/www.svu.edu.eg\/faculties\/vet\/wp-json\/wp\/v2\/media?parent=668"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}