Search

Your search keyword '"Ghesquiere, Bart"' showing total 94 results
Start Over Author "Ghesquiere, Bart" Search Limiters Available in Library Collection
94 results on '"Ghesquiere, Bart"'

3. Tracer metabolomics reveals the role of aldose reductase in glycosylation

Author

Radenkovic, Silvia, Ligezka, Anna N., Mokashi, Sneha S., Driesen, Karen, Dukes-Rimsky, Lynn, Preston, Graeme, Owuocha, Luckio F., Sabbagh, Leila, Mousa, Jehan, Lam, Christina, Edmondson, Andrew, Larson, Austin, Schultz, Matthew, Vermeersch, Pieter, Cassiman, David, Witters, Peter, Beamer, Lesa J., Kozicz, Tamas, Flanagan-Steet, Heather, Ghesquière, Bart, and Morava, Eva

Published
2023
Full Text
View/download PDF

6. Antimetabolic cooperativity with the clinically approved l-asparaginase and tyrosine kinase inhibitors to eradicate CML stem cells

Author

Trinh, Anne, Khamari, Raeeka, Fovez, Quentin, Mahon, François-Xavier, Turcq, Béatrice, Bouscary, Didier, Maboudou, Patrice, Joncquel, Marie, Coiteux, Valérie, Germain, Nicolas, Laine, William, Dekiouk, Salim, Jean-Pierre, Sandrine, Maguer-Satta, Veronique, Ghesquiere, Bart, Idziorek, Thierry, Quesnel, Bruno, Kluza, Jerome, and Marchetti, Philippe

Published
2022
Full Text
View/download PDF

9. Neutrophils Fuel Effective Immune Responses through Gluconeogenesis and Glycogenesis

Author

Sadiku, Pranvera, Willson, Joseph A., Ryan, Eilise M., Sammut, David, Coelho, Patricia, Watts, Emily R., Grecian, Robert, Young, Jason M., Bewley, Martin, Arienti, Simone, Mirchandani, Ananda S., Sanchez Garcia, Manuel A., Morrison, Tyler, Zhang, Ailing, Reyes, Leila, Griessler, Tobias, Jheeta, Privjyot, Paterson, Gordon G., Graham, Christopher J., Thomson, John P., Baillie, Kenneth, Thompson, A.A. Roger, Morgan, Jessie-May, Acosta-Sanchez, Abel, Dardé, Veronica M., Duran, Jordi, Guinovart, Joan J., Rodriguez-Blanco, Gio, Von Kriegsheim, Alex, Meehan, Richard R., Mazzone, Massimiliano, Dockrell, David H., Ghesquiere, Bart, Carmeliet, Peter, Whyte, Moira K.B., and Walmsley, Sarah R.

Published
2021
Full Text
View/download PDF

10. Macrophage-derived glutamine boosts satellite cells and muscle regeneration

Author

Shang, Min, Cappellesso, Federica, Amorim, Ricardo, Serneels, Jens, Virga, Federico, Eelen, Guy, Carobbio, Stefania, Rincon, Melvin Y., Maechler, Pierre, De Bock, Katrien, Ho, Ping-Chih, Sandri, Marco, Ghesquiere, Bart, Carmeliet, Peter, Di Matteo, Mario, Berardi, Emanuele, and Mazzone, Massimiliano

Subjects
Muscles -- Regeneration, Physiological research, Glutamine -- Physiological aspects, Macrophages -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Muscle regeneration is sustained by infiltrating macrophages and the consequent activation of satellite cells.sup.1-4. Macrophages and satellite cells communicate in different ways.sup.1-5, but their metabolic interplay has not been investigated. Here we show, in a mouse model, that muscle injuries and ageing are characterized by intra-tissue restrictions of glutamine. Low levels of glutamine endow macrophages with the metabolic ability to secrete glutamine via enhanced glutamine synthetase (GS) activity, at the expense of glutamine oxidation mediated by glutamate dehydrogenase 1 (GLUD1). Glud1-knockout macrophages display constitutively high GS activity, which prevents glutamine shortages. The uptake of macrophage-derived glutamine by satellite cells through the glutamine transporter SLC1A5 activates mTOR and promotes the proliferation and differentiation of satellite cells. Consequently, macrophage-specific deletion or pharmacological inhibition of GLUD1 improves muscle regeneration and functional recovery in response to acute injury, ischaemia or ageing. Conversely, SLC1A5 blockade in satellite cells or GS inactivation in macrophages negatively affects satellite cell functions and muscle regeneration. These results highlight the metabolic crosstalk between satellite cells and macrophages, in which macrophage-derived glutamine sustains the functions of satellite cells. Thus, the targeting of GLUD1 may offer therapeutic opportunities for the regeneration of injured or aged muscles. Mouse models of muscle injuries and ageing characterized by low levels of intra-tissue glutamine are ameliorated by macrophage-specific deletion or systemic pharmacological inhibition of glutamate dehydrogenase 1, which results in constitutively high activity of glutamine synthetase., Author(s): Min Shang [sup.1] [sup.2] , Federica Cappellesso [sup.1] [sup.2] , Ricardo Amorim [sup.1] [sup.2] [sup.3] [sup.4] [sup.5] , Jens Serneels [sup.1] [sup.2] , Federico Virga [sup.1] [sup.2] [sup.6] [sup.7] [...]

Published
2020
Full Text
View/download PDF

11. Differential roles for the oxygen sensing enzymes PHD1 and PHD3 in the regulation of neutrophil metabolism and function

Author

Watts, Emily, primary, Willison, Joseph, additional, Arienti, Simone, additional, Sadiku, Pranvera, additional, Coelho, Patricia, additional, Sanchez-Garcia, Manuel, additional, Zhang, Ailiang, additional, Murphy, Fiona, additional, Dickinson, Rebecca, additional, Mirchandani, Ananda, additional, Morrison, Tyler, additional, Lewis, Amy, additional, Vermaelen, Wesley, additional, Ghesquiere, Bart, additional, Carmeliet, Peter, additional, Mazzone, Massimilliano, additional, Maxwell, Patrick, additional, Pugh, Christopher, additional, Dockrell, David, additional, Whyte, Moira, additional, and Walmsley, Sarah, additional

Published
2023
Full Text
View/download PDF

12. A roadmap for interpreting 13C metabolite labeling patterns from cells

Author

Buescher, Joerg M, Antoniewicz, Maciek R, Boros, Laszlo G, Burgess, Shawn C, Brunengraber, Henri, Clish, Clary B, DeBerardinis, Ralph J, Feron, Olivier, Frezza, Christian, Ghesquiere, Bart, Gottlieb, Eyal, Hiller, Karsten, Jones, Russell G, Kamphorst, Jurre J, Kibbey, Richard G, Kimmelman, Alec C, Locasale, Jason W, Lunt, Sophia Y, Maddocks, Oliver DK, Malloy, Craig, Metallo, Christian M, Meuillet, Emmanuelle J, Munger, Joshua, Nöh, Katharina, Rabinowitz, Joshua D, Ralser, Markus, Sauer, Uwe, Stephanopoulos, Gregory, St-Pierre, Julie, Tennant, Daniel A, Wittmann, Christoph, Heiden, Matthew G Vander, Vazquez, Alexei, Vousden, Karen, Young, Jamey D, Zamboni, Nicola, and Fendt, Sarah-Maria

Subjects
Biological Sciences, Industrial Biotechnology, Bioengineering, Nutrition, Generic health relevance, Animals, Carbon Isotopes, Cell Survival, Humans, Isotope Labeling, Metabolic Networks and Pathways, Engineering, Technology, Biotechnology, Agricultural biotechnology, Industrial biotechnology, Medical biotechnology
Abstract

Measuring intracellular metabolism has increasingly led to important insights in biomedical research. (13)C tracer analysis, although less information-rich than quantitative (13)C flux analysis that requires computational data integration, has been established as a time-efficient method to unravel relative pathway activities, qualitative changes in pathway contributions, and nutrient contributions. Here, we review selected key issues in interpreting (13)C metabolite labeling patterns, with the goal of drawing accurate conclusions from steady state and dynamic stable isotopic tracer experiments.

Published
2015

13. Quiescent Endothelial Cells Upregulate Fatty Acid β-Oxidation for Vasculoprotection via Redox Homeostasis

Author

Kalucka, Joanna, Bierhansl, Laura, Conchinha, Nadine Vasconcelos, Missiaen, Rindert, Elia, Ilaria, Brüning, Ulrike, Scheinok, Samantha, Treps, Lucas, Cantelmo, Anna Rita, Dubois, Charlotte, de Zeeuw, Pauline, Goveia, Jermaine, Zecchin, Annalisa, Taverna, Federico, Morales-Rodriguez, Francisco, Brajic, Aleksandra, Conradi, Lena-Christin, Schoors, Sandra, Harjes, Ulrike, Vriens, Kim, Pilz, Gregor-Alexander, Chen, Rongyuan, Cubbon, Richard, Thienpont, Bernard, Cruys, Bert, Wong, Brian W., Ghesquière, Bart, Dewerchin, Mieke, De Bock, Katrien, Sagaert, Xavier, Jessberger, Sebastian, Jones, Elizabeth A.V., Gallez, Bernard, Lambrechts, Diether, Mazzone, Massimiliano, Eelen, Guy, Li, Xuri, Fendt, Sarah-Maria, and Carmeliet, Peter

Published
2018
Full Text
View/download PDF

14. Impairment of Angiogenesis by Fatty Acid Synthase Inhibition Involves mTOR Malonylation

Author

Bruning, Ulrike, Morales-Rodriguez, Francisco, Kalucka, Joanna, Goveia, Jermaine, Taverna, Federico, Queiroz, Karla C.S., Dubois, Charlotte, Cantelmo, Anna Rita, Chen, Rongyuan, Loroch, Stefan, Timmerman, Evy, Caixeta, Vanessa, Bloch, Katarzyna, Conradi, Lena-Christin, Treps, Lucas, Staes, An, Gevaert, Kris, Tee, Andrew, Dewerchin, Mieke, Semenkovich, Clay F., Impens, Francis, Schilling, Birgit, Verdin, Eric, Swinnen, Johannes V., Meier, Jordan L., Kulkarni, Rhushikesh A., Sickmann, Albert, Ghesquière, Bart, Schoonjans, Luc, Li, Xuri, Mazzone, Massimiliano, and Carmeliet, Peter

Published
2018
Full Text
View/download PDF

16. Serine Synthesis via PHGDH Is Essential for Heme Production in Endothelial Cells

Author

Vandekeere, Saar, Dubois, Charlotte, Kalucka, Joanna, Sullivan, Mark R., García-Caballero, Melissa, Goveia, Jermaine, Chen, Rongyuan, Diehl, Frances F., Bar-Lev, Libat, Souffreau, Joris, Pircher, Andreas, Kumar, Saran, Vinckier, Stefan, Hirabayashi, Yoshio, Furuya, Shigeki, Schoonjans, Luc, Eelen, Guy, Ghesquière, Bart, Keshet, Eli, Li, Xuri, Vander Heiden, Matthew G., Dewerchin, Mieke, and Carmeliet, Peter

Published
2018
Full Text
View/download PDF

17. Cardiac Microvascular Endothelial Cells in Pressure Overload–Induced Heart Disease

Author

Trenson, Sander, Hermans, Hadewich, Craps, Sander, Pokreisz, Peter, de Zeeuw, Pauline, Van Wauwe, Jore, Gillijns, Hilde, Veltman, Denise, Wei, Fangfei, Caluwé, Ellen, Gijsbers, Rik, Baatsen, Pieter, Staessen, Jan A., Ghesquiere, Bart, Carmeliet, Peter, Rega, Filip, Meuris, Bart, Meyns, Bart, Oosterlinck, Wouter, Duchenne, Jürgen, Goetschalckx, Kaatje, Voigt, Jens-Uwe, Herregods, Marie-Christine, Herijgers, Paul, Luttun, Aernout, and Janssens, Stefan

Published
2021
Full Text
View/download PDF

19. Hypoxia drives murine neutrophil protein scavenging to maintain central carbon metabolism

Author

Watts, Emily R., Howden, Andrew J.M., Morrison, Tyler, Sadiku, Pranvera, Hukelmann, Jens, von Kriegsheim, Alex, Ghesquiere, Bart, Murphy, Fiona, Mirchandani, Ananda S., Humphries, Duncan C., Grecian, Robert, Ryan, Eilise M., Coelho, Patricia, Blanco, Gio Rodriguez, Plant, Tracie M., Dickinson, Rebecca S., Finch, Andy, Vermaelen, Wesley, Cantrell, Doreen A., Whyte, Moira K., and Walmsley, Sarah R.

Subjects
Metabolism -- Research, Medical research, Medicine, Experimental, Neutrophils -- Physiological aspects -- Health aspects, Hypoxia -- Physiological aspects, Health care industry
Abstract

Limiting dysfunctional neutrophilic inflammation while preserving effective immunity requires a better understanding of the processes that dictate neutrophil function in the tissues. Quantitative mass-spectrometry identified how inflammatory murine neutrophils regulated expression of cell surface receptors, signal transduction networks, and metabolic machinery to shape neutrophil phenotypes in response to hypoxia. Through the tracing of labeled amino acids into metabolic enzymes, proinflammatory mediators, and granule proteins, we demonstrated that ongoing protein synthesis shapes the neutrophil proteome. To maintain energy supplies in the tissues, neutrophils consumed extracellular proteins to fuel central carbon metabolism. The physiological stresses of hypoxia and hypoglycemia, characteristic of inflamed tissues, promoted this extracellular protein scavenging with activation of the lysosomal compartment, further driving exploitation of the protein-rich inflammatory milieu. This study provides a comprehensive map of neutrophil proteomes, analysis of which has led to the identification of active catabolic and anabolic pathways that enable neutrophils to sustain synthetic and effector functions in the tissues., Introduction The rapid recruitment of innate immune cells is critical for containing and eradicating infection and the restoration of normal tissue homeostasis. To enable effective immune responses in the tissues, [...]

Published
2021
Full Text
View/download PDF

21. Deletion or Inhibition of the Oxygen Sensor PHD1 Protects against Ischemic Stroke via Reprogramming of Neuronal Metabolism

Author

Quaegebeur, Annelies, Segura, Inmaculada, Schmieder, Roberta, Verdegem, Dries, Decimo, Ilaria, Bifari, Francesco, Dresselaers, Tom, Eelen, Guy, Ghosh, Debapriva, Davidson, Shawn M., Schoors, Sandra, Broekaert, Dorien, Cruys, Bert, Govaerts, Kristof, De Legher, Carla, Bouché, Ann, Schoonjans, Luc, Ramer, Matt S., Hung, Gene, Bossaert, Goele, Cleveland, Don W., Himmelreich, Uwe, Voets, Thomas, Lemmens, Robin, Bennett, C. Frank, Robberecht, Wim, De Bock, Katrien, Dewerchin, Mieke, Ghesquière, Bart, Fendt, Sarah-Maria, and Carmeliet, Peter

Published
2016
Full Text
View/download PDF

22. NRF2 activation reprogrammes defects in oxidative metabolism to restore macrophage function in COPD

Author

Ryan, Eilise, Sadiku, Pranvera, Coelho, Patricia, Watts, Emily R, Zhang, Ailiang, Howden, Andrew J M, Sanchez Garcia, Manuel Alejandro, Bewley, Martin A., Cole, Joby, McHugh, Brian, Vermaelen, Wesley, Ghesquiere, Bart, Carmeliet, Peter, Rodriguez Blanco, Giovanny, von Kriegsheim, Alexander, Sanchez, Yolanda, Rumsey, William, Callahan, James F, Cooper, George, Parkinson, Nicholas, Baillie, J Kenneth, Cantrell, Doreen, McCafferty, John, Choudhury, Gourab, Singh, David, Dockrell, David H, Whyte, Moira K B, and Walmsley, Sarah R

Abstract

Rationale: COPD (Chronic Obstructive Pulmonary Disease) is a disease characterized by persistent airway inflammation and disordered macrophage function. The extent to which alterations in macrophage bioenergetics contribute to impaired antioxidant responses and disease pathogenesis has yet to be fully delineated. Objectives: Through the study of COPD alveolar (AM) and peripheral monocyte-derived (MDM) macrophages, we sought to establish if intrinsic defects in core metabolic processes drive macrophage dysfunction and redox imbalance. Methods: AM and MDM from COPD and healthy donors underwent functional, metabolic and transcriptional profiling. Results: We observe that AM and MDM from COPD donors display a critical depletion in glycolytic and mitochondrial respiration derived energy reserves and an over reliance on glycolysis as a source for ATP, resulting in reduced energy status. Defects in oxidative metabolism extend to an impaired redox balance associated with defective expression of the NADPH generating enzyme, malic enzyme 1, a known target of the anti-oxidant transcription factor NRF2. Consequently, selective activation of NRF2 resets the COPD transcriptome, resulting in increased generation of TCA cycle intermediaries, improved energetic status, favorable redox balance and a recovery of macrophage function. Conclusion: In COPD an inherent loss of metabolic plasticity leads to metabolic exhaustion and reduced redox capacity which can be rescued by activation of the NRF2 pathway. Targeting these defects, via NRF2 augmentation, may therefore present an attractive therapeutic strategy for the treatment of the aberrant airway inflammation described in COPD.

Published
2023

23. Prolyl hydroxylase 2 inactivation enhances glycogen storage and promotes excessive neutrophilic responses

Author

Sadiku, Pranvera, Willson, Joseph A., Dickinson, Rebecca S., Murphy, Fiona, Harris, Alison J., Lewis, Amy, Sammut, David, Mirchandani, Ananda S., Ryan, Eilise, Watts, Emily R., Thompson, A.A. Roger, Marriott, Helen M., Dockrell, David H., Taylor, Cormac T., Schneider, Martin, Maxwell, Patrick H., Chilvers, Edwin R., Mazzone, Massimilliano, Moral, Veronica, Pugh, Chris W., Ratcliffe, Peter J., Schofield, Christopher J., Ghesquiere, Bart, Carmeliet, Peter, Whyte, Moira K.B., and Walmsley, Sarah R.

Subjects
Hydroxylases -- Health aspects, Glycogen -- Health aspects, Neutrophils -- Health aspects, Health care industry
Abstract

Fully activated innate immune cells are required for effective responses to infection, but their prompt deactivation and removal are essential for limiting tissue damage. Here, we have identified a critical role for the prolyl hydroxylase enzyme Phd2 in maintaining the balance between appropriate, predominantly neutrophil -mediated pathogen clearance and resolution of the innate immune response. We demonstrate that myeloid-specific loss of Phd2 resulted in an exaggerated inflammatory response to Streptococcus pneumonia, with increases in neutrophil motility, functional capacity, and survival. These enhanced neutrophil responses were dependent upon increases in glycolytic flux and glycogen stores. Systemic administration of a HIF-prolyl hydroxylase inhibitor replicated the Phd2-deficient phenotype of delayed inflammation resolution. Together, these data identify Phd2 as the dominant HIF-hydroxylase in neutrophils under normoxic conditions and link intrinsic regulation of glycolysis and glycogen stores to the resolution of neutrophil-mediated inflammatory responses. These results demonstrate the therapeutic potential of targeting metabolic pathways in the treatment of inflammatory disease., Introduction Inappropriate or persistent neutrophilic inflammation is implicated in a number of disease states exemplified by acute lung injury responses and chronic obstructive pulmonary disease. There are, to date, no [...]

Published
2017
Full Text
View/download PDF

24. Partial and Transient Reduction of Glycolysis by PFKFB3 Blockade Reduces Pathological Angiogenesis

Author

Schoors, Sandra, De Bock, Katrien, Cantelmo, Anna Rita, Georgiadou, Maria, Ghesquière, Bart, Cauwenberghs, Sandra, Kuchnio, Anna, Wong, Brian W., Quaegebeur, Annelies, Goveia, Jermaine, Bifari, Francesco, Wang, Xingwu, Blanco, Raquel, Tembuyser, Bieke, Cornelissen, Ivo, Bouché, Ann, Vinckier, Stefan, Diaz-Moralli, Santiago, Gerhardt, Holger, Telang, Sucheta, Cascante, Marta, Chesney, Jason, Dewerchin, Mieke, and Carmeliet, Peter

Published
2014
Full Text
View/download PDF

25. RRM2 enhances MYCN-driven neuroblastoma formation and acts as a synergistic target with CHK1 inhibition

Author

Nunes, Carolina, primary, Depestel, Lisa, additional, Mus, Liselot, additional, Keller, Kaylee M., additional, Delhaye, Louis, additional, Louwagie, Amber, additional, Rishfi, Muhammad, additional, Whale, Alex, additional, Kara, Neesha, additional, Andrews, Simon R., additional, Dela Cruz, Filemon, additional, You, Daoqi, additional, Siddiquee, Armaan, additional, Cologna, Camila Takeno, additional, De Craemer, Sam, additional, Dolman, Emmy, additional, Bartenhagen, Christoph, additional, De Vloed, Fanny, additional, Sanders, Ellen, additional, Eggermont, Aline, additional, Bekaert, Sarah-Lee, additional, Van Loocke, Wouter, additional, Bek, Jan Willem, additional, Dewyn, Givani, additional, Loontiens, Siebe, additional, Van Isterdael, Gert, additional, Decaesteker, Bieke, additional, Tilleman, Laurentijn, additional, Van Nieuwerburgh, Filip, additional, Vermeirssen, Vanessa, additional, Van Neste, Christophe, additional, Ghesquiere, Bart, additional, Goossens, Steven, additional, Eyckerman, Sven, additional, De Preter, Katleen, additional, Fischer, Matthias, additional, Houseley, Jon, additional, Molenaar, Jan, additional, De Wilde, Bram, additional, Roberts, Stephen S., additional, Durinck, Kaat, additional, and Speleman, Frank, additional

Published
2022
Full Text
View/download PDF

26. RRM2 enhances MYCN-driven neuroblastoma formation and acts as a synergistic target with CHK1 inhibition

Author

Afd Pharmaceutics, Pharmaceutics, Nunes, Carolina, Depestel, Lisa, Mus, Liselot, Keller, Kaylee M., Delhaye, Louis, Louwagie, Amber, Rishfi, Muhammad, Whale, Alex, Kara, Neesha, Andrews, Simon R., Cruz, Filemon Dela, You, Daoqi, Siddiquee, Armaan, Cologna, Camila Takeno, De Craemer, Sam, Dolman, Emmy, Bartenhagen, Christoph, De Vloed, Fanny, Sanders, Ellen, Eggermont, Aline, Bekaert, Sarah Lee, Van Loocke, Wouter, Bek, Jan Willem, Dewyn, Givani, Loontiens, Siebe, Van Isterdael, Gert, Decaesteker, Bieke, Tilleman, Laurentijn, Van Nieuwerburgh, Filip, Vermeirssen, Vanessa, Van Neste, Christophe, Ghesquiere, Bart, Goossens, Steven, Eyckerman, Sven, De Preter, Katleen, Fischer, Matthias, Houseley, Jon, Molenaar, Jan, De Wilde, Bram, Roberts, Stephen S., Durinck, Kaat, Speleman, Frank, Afd Pharmaceutics, Pharmaceutics, Nunes, Carolina, Depestel, Lisa, Mus, Liselot, Keller, Kaylee M., Delhaye, Louis, Louwagie, Amber, Rishfi, Muhammad, Whale, Alex, Kara, Neesha, Andrews, Simon R., Cruz, Filemon Dela, You, Daoqi, Siddiquee, Armaan, Cologna, Camila Takeno, De Craemer, Sam, Dolman, Emmy, Bartenhagen, Christoph, De Vloed, Fanny, Sanders, Ellen, Eggermont, Aline, Bekaert, Sarah Lee, Van Loocke, Wouter, Bek, Jan Willem, Dewyn, Givani, Loontiens, Siebe, Van Isterdael, Gert, Decaesteker, Bieke, Tilleman, Laurentijn, Van Nieuwerburgh, Filip, Vermeirssen, Vanessa, Van Neste, Christophe, Ghesquiere, Bart, Goossens, Steven, Eyckerman, Sven, De Preter, Katleen, Fischer, Matthias, Houseley, Jon, Molenaar, Jan, De Wilde, Bram, Roberts, Stephen S., Durinck, Kaat, and Speleman, Frank

Published
2022

27. RRM2 enhances MYCN-driven neuroblastoma formation and acts as a synergistic target with CHK1 inhibition

Author

Nunes, Carolina, Depestel, Lisa, Mus, Liselot, Keller, Kaylee M., Delhaye, Louis, Louwagie, Amber, Rishfi, Muhammad, Whale, Alex, Kara, Neesha, Andrews, Simon R., Dela Cruz, Filemon, You, Daoqi, Siddiquee, Armaan, Cologna, Camila Takeno, De Craemer, Sam, Dolman, Emmy, Bartenhagen, Christoph, De Vloed, Fanny, Sanders, Ellen, Eggermont, Aline, Bekaert, Sarah-Lee, Van Loocke, Wouter, Bek, Jan Willem, Dewyn, Givani, Loontiens, Siebe, Van Isterdael, Gert, Decaesteker, Bieke, Tilleman, Laurentijn, Van Nieuwerburgh, Filip, Vermeirssen, Vanessa, Van Neste, Christophe, Ghesquiere, Bart, Goossens, Steven, Eyckerman, Sven, De Preter, Katleen, Fischer, Matthias, Houseley, Jon, Molenaar, Jan, De Wilde, Bram, Roberts, Stephen S., Durinck, Kaat, Speleman, Frank, Nunes, Carolina, Depestel, Lisa, Mus, Liselot, Keller, Kaylee M., Delhaye, Louis, Louwagie, Amber, Rishfi, Muhammad, Whale, Alex, Kara, Neesha, Andrews, Simon R., Dela Cruz, Filemon, You, Daoqi, Siddiquee, Armaan, Cologna, Camila Takeno, De Craemer, Sam, Dolman, Emmy, Bartenhagen, Christoph, De Vloed, Fanny, Sanders, Ellen, Eggermont, Aline, Bekaert, Sarah-Lee, Van Loocke, Wouter, Bek, Jan Willem, Dewyn, Givani, Loontiens, Siebe, Van Isterdael, Gert, Decaesteker, Bieke, Tilleman, Laurentijn, Van Nieuwerburgh, Filip, Vermeirssen, Vanessa, Van Neste, Christophe, Ghesquiere, Bart, Goossens, Steven, Eyckerman, Sven, De Preter, Katleen, Fischer, Matthias, Houseley, Jon, Molenaar, Jan, De Wilde, Bram, Roberts, Stephen S., Durinck, Kaat, and Speleman, Frank

Abstract

High-risk neuroblastoma, a pediatric tumor originating from the sympathetic nervous system, has a low mutation load but highly recurrent somatic DNA copy number variants. Previously, segmental gains and/or amplifications allowed identification of drivers for neuroblastoma development. Using this approach, combined with gene dosage impact on expression and survival, we identified ribonucleotide reductase subunit M2 (RRM2) as a candidate dependency factor further supported by growth inhibition upon in vitro knockdown and accelerated tumor formation in a neuroblastoma zebrafish model coexpressing human RRM2 with MYCN. Forced RRM2 induction alleviates excessive replicative stress induced by CHK1 inhibition, while high RRM2 expression in human neuroblastomas correlates with high CHK1 activity. MYCN-driven zebrafish tumors with RRM2 co-overexpression exhibit differentially expressed DNA repair genes in keeping with enhanced ATR-CHK1 signaling activity. In vitro, RRM2 inhibition enhances intrinsic replication stress checkpoint addiction. Last, combinatorial RRM2-CHK1 inhibition acts synergistic in high-risk neuroblastoma cell lines and patient-derived xenograft models, illustrating the therapeutic potential.

Published
2022

28. Fatty acid carbon is essential for dNTP synthesis in endothelial cells

Author

Schoors, Sandra, Bruning, Ulrike, Missiaen, Rindert, Queiroz, Karla C.S., Borgers, Gitte, Elia, Ilaria, Zecchin, Annalisa, Cantelmo, Anna Rita, Christen, Stefan, Goveia, Jermaine, Heggermont, Ward, Godde, Lucica, Vinckier, Stefan, Van Veldhoven, Paul P., Eelen, Guy, Schoonjans, Luc, Gerhardt, Holger, Dewerchin, Mieke, Baes, Myriam, De Bock, Katrien, Ghesquiere, Bart, Lunt, Sophia Y., Fendt, Sarah-Maria, and Carmeliet, Peter

Subjects
Endothelium -- Physiological aspects, Fatty acids -- Physiological aspects, Deoxyribonucleotides -- Physiological aspects, Carbon -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The metabolism of endothelial cells during vessel sprouting remains poorly studied. Here we report that endothelial loss of CPT1A, a rate-limiting enzyme of fatty acid oxidation (FAO), causes vascular sprouting defects due to impaired proliferation, not migration, of human and murine endothelial cells. Reduction of FAO in endothelial cells did not cause energy depletion or disturb redox homeostasis, but impaired de novo nucleotide synthesis for DNA replication. Isotope labelling studies in control endothelial cells showed that fatty acid carbons substantially replenished the Krebs cycle, and were incorporated into aspartate (a nucleotide precursor), uridine monophosphate (a precursor of pyrimidine nucleoside triphosphates) and DNA. CPT1A silencing reduced these processes and depleted endothelial cell stores of aspartate and deoxyribonucleoside triphosphates. Acetate (metabolized to acetyl-CoA, thereby substituting for the depleted FAO-derived acetyl-CoA) or a nucleoside mix rescued the phenotype of CPT1A-silenced endothelial cells. Finally, CPT1 blockade inhibited pathological ocular angiogenesis in mice, suggesting a novel strategy for blocking angiogenesis., Angiogenesis relies on the proliferation and migration of endothelial cells (1). The importance of endothelial cell proliferation for expansive growth of the vascular network has long been recognized (2). While [...]

Published
2015
Full Text
View/download PDF

30. Antizyme Inhibitor 1 regulates matrikine expression and enhances the metastatic potential of aggressive primary prostate cancer

Author

Van den Broeck, Thomas, primary, Moris, Lisa, additional, Gevaert, Thomas, additional, Davicioni, Elai, additional, Boeckx, Bram, additional, Lambrechts, Diether, additional, Helsen, Christine, additional, Handle, Florian, additional, Ghesquiere, Bart, additional, Soenen, Stefaan, additional, Smeets, Elien, additional, Eerlings, Roy, additional, El Kharraz, Sarah, additional, Devlies, Wout, additional, Karnes, R. Jeffrey, additional, Lotan, Tamara, additional, Van Poppel, Hendrik, additional, Joniau, Steven, additional, and Claessens, Frank, additional

Published
2022
Full Text
View/download PDF

31. ANTIMETABOLIC COOPERATIVITY WITH THE CLINICALLY-APPROVED L-ASPARAGINASE AND TYROSINE KINASE INHIBITORS TO ERADICATE CML STEM CELLS

Author

Trinh, Anne, primary, Khamari, Raeeka, additional, Fovez, Quentin, additional, Mahon, François-Xavier, additional, Turcq, Béatrice, additional, Bouscary, Didier, additional, Maboudou, Patrice, additional, Joncquel, Marie, additional, Coiteux, Valérie, additional, Germain, Nicolas, additional, Laine, William, additional, Dekiouk, Salim, additional, Jean-Pierre, Sandrine, additional, Maguer-Satta, Veronique, additional, Ghesquiere, Bart, additional, Idziorek, Thierry, additional, Quesnel, Bruno, additional, Kluza, Jerome, additional, and Marchetti, Philippe, additional

Published
2021
Full Text
View/download PDF

32. Metabolism of stromal and immune cells in health and disease

Author

Ghesquiere, Bart, Wong, Brian W., Kuchnio, Anna, and Carmeliet, Peter

Subjects
Vascular endothelium -- Research, Oncology, Experimental, Immune system -- Research, Cancer cells -- Research, Cancer -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Cancer cells have been at the centre of cell metabolism research, but the metabolism of stromal and immune cells has received less attention. Nonetheless, these cells influence the progression of malignant, inflammatory and metabolic disorders. Here we discuss the metabolic adaptations of stromal and immune cells in health and disease, and highlight how metabolism determines their differentiation and function., Stromal cells are connective cells that support parenchymal cells. Aside from endothelial cells (ECs), which build blood vessels to supply oxygen and nutrients (1,2), other stromal cells include fibroblasts, which [...]

Published
2014
Full Text
View/download PDF

33. A type I IFN, prothrombotic hyperinflammatory neutrophil signature is distinct for COVID-19 ARDS­­­

Author

Reyes, Leila, Sanchez Garcia, Manuel Alejandro, Morrison, Tyler, Howden, Andrew J M, Watts, Emily R, Arienti, Simone, Sadiku, Pranvera, Coelho, Patricia, Mirchandani, Ananda S, Zhang, Ailiang, Hope, David, Clark , Sarah K, Singleton, Jo, Johnston, Shonna, Grecian, Rob, Poon, Azin S., McNamara, Sarah, Harper, Isla, Fourman, Max Head, Brenes, Alejandro J, Pathak, Shalini, Lloyd, Amy, Rodriguez Blanco, Gio, von Kriegsheim, Alexander, Ghesquiere, Bart, Vermaelen, Wesley, Cologna, Camilla T, Dhaliwal, Kevin, Hirani, Nik, Dockrell, David H, Whyte, Moira K B, Griffith, David M, Cantrell, Doreen, and Walmsley, Sarah R

Abstract

Background: Acute respiratory distress syndrome (ARDS) is a severe critical condition with a high mortality that is currently in focus given that it is associated with mortality caused by coronavirus disease 2019 (COVID-19). Neutrophils play a key role in the lung injury characteristic of non-COVID-19 ARDS and there is also accumulating evidence of neutrophil mediated lung injury in patients who succumb to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Methods: We undertook a functional proteomic and metabolomic survey of circulating neutrophil populations, comparing patients with COVID-19 ARDS and non-COVID-19 ARDS to understand the molecular basis of neutrophil dysregulation.Results: Expansion of the circulating neutrophil compartment and the presence of activated low and normal density mature and immature neutrophil populations occurs in ARDS, irrespective of cause. Release of neutrophil granule proteins, neutrophil activation of the clotting cascade and upregulation of the Mac-1 platelet binding complex with formation of neutrophil platelet aggregates is exaggerated in COVID-19 ARDS. Importantly, activation of components of the neutrophil type I interferon responses is seen in ARDS following infection with SARS-CoV-2, with associated rewiring of neutrophil metabolism, and the upregulation of antigen processing and presentation. Whilst dexamethasone treatment constricts the immature low density neutrophil population, it does not impact upon prothrombotic hyperinflammatory neutrophil signatures.Conclusions: Given the crucial role of neutrophils in ARDS and the evidence of a disordered myeloid response observed in COVID-19 patients, this work maps the molecular basis for neutrophil reprogramming in the distinct clinical entities of COVID-19 and non-COVID-19 ARDS.

Published
2021

34. Human and mouse non‐targeted metabolomics identify 1,5‐anhydroglucitol as SGLT2‐dependent glycemic marker

Author

Kappel, Ben A., primary, Moellmann, Julia, additional, Thiele, Kirsten, additional, Rau, Matthias, additional, Artati, Anna, additional, Adamski, Jerzy, additional, Ghesquiere, Bart, additional, Schuett, Katharina, additional, Romeo, Francesco, additional, Stoehr, Robert, additional, Marx, Nikolaus, additional, Federici, Massimo, additional, and Lehrke, Michael, additional

Published
2021
Full Text
View/download PDF

35. ­­­­­­­A type I IFN, prothrombotic hyperinflammatory neutrophil signature is distinct for COVID-19 ARDS­­­

Author

Reyes, Leila, primary, A. Sanchez-Garcia, Manuel, additional, Morrison, Tyler, additional, Howden, Andy J. M., additional, Watts, Emily R., additional, Arienti, Simone, additional, Sadiku, Pranvera, additional, Coelho, Patricia, additional, Mirchandani, Ananda S., additional, Zhang, Ailiang, additional, Hope, David, additional, Clark, Sarah K., additional, Singleton, Jo, additional, Johnston, Shonna, additional, Grecian, Robert, additional, Poon, Azin, additional, McNamara, Sarah, additional, Harper, Isla, additional, Fourman, Max Head, additional, Brenes, Alejandro J., additional, Pathak, Shalini, additional, Lloyd, Amy, additional, Blanco, Giovanny Rodriguez, additional, von Kriegsheim, Alex, additional, Ghesquiere, Bart, additional, Vermaelen, Wesley, additional, Cologna, Camila T., additional, Dhaliwal, Kevin, additional, Hirani, Nik, additional, Dockrell, David H., additional, Whyte, Moira K. B., additional, Griffith, David, additional, Cantrell, Doreen A., additional, and Walmsley, Sarah R., additional

Published
2021
Full Text
View/download PDF

36. Alternative glycosylation controls endoplasmic reticulum dynamics and tubular extension in mammalian cells

Author

Kerselidou, Despoina, primary, Dohai, Bushra Saeed, additional, Nelson, David R., additional, Daakour, Sarah, additional, De Cock, Nicolas, additional, Hassoun, Zahra Al Oula, additional, Kim, Dae-Kyum, additional, Olivet, Julien, additional, El Assal, Diana C., additional, Jaiswal, Ashish, additional, Alzahmi, Amnah, additional, Saha, Deeya, additional, Pain, Charlotte, additional, Matthijssens, Filip, additional, Lemaitre, Pierre, additional, Herfs, Michael, additional, Chapuis, Julien, additional, Ghesquiere, Bart, additional, Vertommen, Didier, additional, Kriechbaumer, Verena, additional, Knoops, Kèvin, additional, Lopez-Iglesias, Carmen, additional, van Zandvoort, Marc, additional, Lambert, Jean-Charles, additional, Hanson, Julien, additional, Desmet, Christophe, additional, Thiry, Marc, additional, Lauersen, Kyle J., additional, Vidal, Marc, additional, Van Vlierberghe, Pieter, additional, Dequiedt, Franck, additional, Salehi-Ashtiani, Kourosh, additional, and Twizere, Jean-Claude, additional

Published
2021
Full Text
View/download PDF

37. Alternative glycosylation controls endoplasmic reticulum dynamics and tubular extension in mammalian cells

Author

Kerselidou, Despoina, Dohai, Bushra Saeed, Nelson, David R., Daakour, Sarah, De Cock, Nicolas, Al Oula Hassoun, Zahra, Kim, Dae-Kyum, Olivet, Julien, El Assal, Diana C., Jaiswal, Ashish, Alzahmi, Amnah, Saha, Deeya, Pain, Charlotte, Matthijssens, Filip, Lemaitre, Pierre, Herfs, Michael, Chapuis, Julien, Ghesquiere, Bart, Vertommen, Didier, Kriechbaumer, Verena, Knoops, Kèvin, Lopez-Iglesias, Carmen, van Zandvoort, Marc, Lambert, Jean-Charles, Hanson, Julien, Desmet, Christophe, Thiry, Marc, Lauersen, Kyle J., Vidal, Marc, Van Vlierberghe, Pieter, Dequiedt, Franck, Salehi-Ashtiani, Kourosh, Twizere, Jean-Claude, Kerselidou, Despoina, Dohai, Bushra Saeed, Nelson, David R., Daakour, Sarah, De Cock, Nicolas, Al Oula Hassoun, Zahra, Kim, Dae-Kyum, Olivet, Julien, El Assal, Diana C., Jaiswal, Ashish, Alzahmi, Amnah, Saha, Deeya, Pain, Charlotte, Matthijssens, Filip, Lemaitre, Pierre, Herfs, Michael, Chapuis, Julien, Ghesquiere, Bart, Vertommen, Didier, Kriechbaumer, Verena, Knoops, Kèvin, Lopez-Iglesias, Carmen, van Zandvoort, Marc, Lambert, Jean-Charles, Hanson, Julien, Desmet, Christophe, Thiry, Marc, Lauersen, Kyle J., Vidal, Marc, Van Vlierberghe, Pieter, Dequiedt, Franck, Salehi-Ashtiani, Kourosh, and Twizere, Jean-Claude

Abstract

The endoplasmic reticulum (ER) is a central eukaryotic organelle with a tubular network made of hairpin proteins linked by hydrolysis of GTP nucleotides. Among post-translational modifications initiated at the ER level, glycosylation is the most common reaction. However, our understanding of the impact of glycosylation on the ER structure remains unclear. Here, we show that Exostosin-1 (EXT1) glycosyltransferase, an enzyme involved in N-glycosylation, is a key regulator of the ER morphology and dynamics. We have integrated multi-omics data and super-resolution imaging to characterize the broad effect of EXT1 inactivation, including the ER shape-dynamics-function relationships in mammalian cells. We have observed that inactivating EXT1 induces cell enlargement and enhances metabolic switches such as protein secretion. In particular, suppressing EXT1 in mouse thymocytes causes developmental dysfunctions associated with the ER network extension. Finally, our data illuminate the physical and functional aspects of the ER proteome-glycome-lipidome-structure axis, with implications in biotechnology and medicine.

Published
2021

38. Alternative glycosylation controls endoplasmic reticulum dynamics and tubular extension in mammalian cells

Author

UCL - SSS/DDUV/PHOS - Protein phosphorylation, Kerselidou, Despoina, Dohai, Bushra Saeed, Nelson, David R., Daakour, Sarah, De Cock, Nicolas, Hassoun, Zahra Al Oula, Kim, Dae-Kyum, Olivet, Julien, El Assal, Diana C., Jaiswal, Ashish, Alzahmi, Amnah, Saha, Deeya, Pain, Charlotte, Matthijssens, Filip, Lemaitre, Pierre, Herfs, Michael, Chapuis, Julien, Ghesquiere, Bart, Vertommen, Didier, Kriechbaumer, Verena, Knoops, Kèvin, Lopez-Iglesias, Carmen, van Zandvoort, Marc, Lambert, Jean-Charles, Hanson, Julien, Desmet, Christophe, Thiry, Marc, Lauersen, Kyle J., Vidal, Marc, Van Vlierberghe, Pieter, Dequiedt, Franck, Salehi-Ashtiani, Kourosh, Twizere, Jean-Claude, UCL - SSS/DDUV/PHOS - Protein phosphorylation, Kerselidou, Despoina, Dohai, Bushra Saeed, Nelson, David R., Daakour, Sarah, De Cock, Nicolas, Hassoun, Zahra Al Oula, Kim, Dae-Kyum, Olivet, Julien, El Assal, Diana C., Jaiswal, Ashish, Alzahmi, Amnah, Saha, Deeya, Pain, Charlotte, Matthijssens, Filip, Lemaitre, Pierre, Herfs, Michael, Chapuis, Julien, Ghesquiere, Bart, Vertommen, Didier, Kriechbaumer, Verena, Knoops, Kèvin, Lopez-Iglesias, Carmen, van Zandvoort, Marc, Lambert, Jean-Charles, Hanson, Julien, Desmet, Christophe, Thiry, Marc, Lauersen, Kyle J., Vidal, Marc, Van Vlierberghe, Pieter, Dequiedt, Franck, Salehi-Ashtiani, Kourosh, and Twizere, Jean-Claude

Abstract

The endoplasmic reticulum (ER) is a central eukaryotic organelle with a tubular network made of hairpin proteins linked by hydrolysis of guanosine triphosphate nucleotides. Among posttranslational modifications initiated at the ER level, glycosylation is the most common reaction. However, our understanding of the impact of glycosylation on the ER structure remains unclear. Here, we show that exostosin-1 (EXT1) glycosyltransferase, an enzyme involved in N-glycosylation, is a key regulator of ER morphology and dynamics. We have integrated multiomics and superresolution imaging to characterize the broad effect of EXT1 inactivation, including the ER shape-dynamics-function relationships in mammalian cells. We have observed that inactivating EXT1 induces cell enlargement and enhances metabolic switches such as protein secretion. In particular, suppressing EXT1 in mouse thymocytes causes developmental dysfunctions associated with the ER network extension. Last, our data illuminate the physical and functional aspects of the ER proteome-glycome-lipidome structure axis, with implications in biotechnology and medicine

Published
2021

39. IL4R alpha Signaling Abrogates Hypoxic Neutrophil Survival and Limits Acute Lung Injury Responses In Vivo

Author

Harris, Alison J, Mirchandani, Ananda S, Lynch, Ruairi W, Murphy, Fiona, Delaney, Liam, Small, Donna, Coelho, Patricia, Watts, Emily R, Sadiku, Pranvera, Griffith, David, Dickinson, Rebecca S, Clark, Eilidh, Willson, Joseph A, Morrison, Tyler, Mazzone, Massimilliano, Carmeliet, Peter, Ghesquiere, Bart, O'Kane, Cecilia, McAuley, Danny, Jenkins, Steve J, Whyte, Moira KB, and Walmsley, Sarah R

Subjects
Science & Technology, hypoxia, Respiratory System, IL-4, INHIBITION, neutrophil, EFFECTOR-CELLS, LIPOPOLYSACCHARIDE, acute respiratory distress syndrome, MECHANISMS, APOPTOSIS, ACTIVATION, HYDROXYLASE, Critical Care Medicine, RESOLUTION, General & Internal Medicine, hypoxia-inducible factor-1 alpha, MACROPHAGES, Life Sciences & Biomedicine, GENE-EXPRESSION
Abstract

Rationale: Acute respiratory distress syndrome is defined by the presence of systemic hypoxia and consequent on disordered neutrophilic inflammation. Local mechanisms limiting the duration and magnitude of this neutrophilic response remain poorly understood. Objectives: To test the hypothesis that during acute lung inflammation tissue production of proresolution type 2 cytokines (IL-4 and IL-13) dampens the proinflammatory effects of hypoxia through suppression of HIF-1α (hypoxia-inducible factor-1α)-mediated neutrophil adaptation, resulting in resolution of lung injury. Methods: Neutrophil activation of IL4Ra (IL-4 receptor α) signaling pathways was explored ex vivo in human acute respiratory distress syndrome patient samples, in vitro after the culture of human peripheral blood neutrophils with recombinant IL-4 under conditions of hypoxia, and in vivo through the study of IL4Ra-deficient neutrophils in competitive chimera models and wild-type mice treated with IL-4. Measurements and Main Results: IL-4 was elevated in human BAL from patients with acute respiratory distress syndrome, and its receptor was identified on patient blood neutrophils. Treatment of human neutrophils with IL-4 suppressed HIF-1α-dependent hypoxic survival and limited proinflammatory transcriptional responses. Increased neutrophil apoptosis in hypoxia, also observed with IL-13, required active STAT signaling, and was dependent on expression of the oxygen-sensing prolyl hydroxylase PHD2. In vivo, IL-4Ra-deficient neutrophils had a survival advantage within a hypoxic inflamed niche; in contrast, inflamed lung treatment with IL-4 accelerated resolution through increased neutrophil apoptosis. Conclusions: We describe an important interaction whereby IL4Rα-dependent type 2 cytokine signaling can directly inhibit hypoxic neutrophil survival in tissues and promote resolution of neutrophil-mediated acute lung injury. ispartof: AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE vol:200 issue:2 pages:235-246 ispartof: location:United States status: published

Published
2019

40. IL4Rα Signaling Abrogates Hypoxic Neutrophil Survival and Limits Acute Lung Injury Responses In Vivo

Author

Harris, Alison J, Mirchandani, Ananda S, Lynch, Ruairi W, Delaney, Liam, Small, Donna, Coelho, Patricia, Watts, Emily R, Sadiku, Pranvera, Griffith, David, Dickinson, Rebecca S, Clark, Eilidh, Willson, Joseph A, Morrison, Tyler, Mazzone, Massimilliano, Carmeliet, Peter, Ghesquiere, Bart, O'Kane, Cecilia, McAuley, Danny, Jenkins, Steve J, Whyte, Moira K B, and Walmsley, Sarah R

Abstract

RATIONALE: Acute respiratory distress syndrome (ARDS) is defined by the presence of systemic hypoxia and consequent upon disordered neutrophilic inflammation. Local mechanisms limiting the duration and magnitude of this neutrophilic response remain poorly understood.OBJECTIVES: We aimed to test the hypothesis that during acute lung inflammation tissue production of pro-resolution type 2 cytokines (IL-4 and IL-13) dampen the pro-inflammatory effects of hypoxia through suppression of Hypoxia Inducible Factor (HIF-1)α-mediated neutrophil adaptation, resulting in resolution of the lung injury.METHODS: Neutrophil activation of IL4Ra signaling pathways were explored ex vivo in human ARDS patient samples, in vitro following the culture of human peripheral blood neutrophils with recombinant IL-4 under conditions of hypoxia, and in vivo, through the study of IL4Ra deficient neutrophils in competitive chimera models and wild-type mice treated with IL-4.MEASUREMENTS AND MAIN RESULTS: IL-4 was elevated in human bronchoalveolar lavage from ARDS patients and its receptor was identified on inflamed lung neutrophils. Treatment of human neutrophils with IL-4 suppressed HIF-1α dependent hypoxic survival and limited pro-inflammatory transcriptional responses. Increased neutrophil apoptosis in hypoxia, also observed with IL-13, required active STAT signaling, and was dependent upon expression of the oxygen sensing prolyl hydroxylase PHD2. In vivo, IL-4Ra-deficient neutrophils had a survival advantage within a hypoxic inflamed niche, in contrast inflamed lung treatment with IL-4 accelerated resolution through increased neutrophil apoptosis.CONCLUSIONS: We describe an important interaction whereby IL4Rα-dependent type 2 cytokine signaling can directly inhibit hypoxic neutrophil survival in tissues and promote resolution of neutrophil mediated acute lung injury. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial License 4.0 (http://creativecommons.org/licenses/by-nc/4.0/.

Published
2019

41. The Metabolic Map into the Pathomechanism and Treatment of PGM1-CDG

Author

Radenkovic, Silvia, Bird, Matthew J., Emmerzaal, T.L., Wong, S.Y.W., Felgueira, Catarina, Stiers, Kyle M., Kozicz, T., Morava, E., Ghesquiere, Bart, Radenkovic, Silvia, Bird, Matthew J., Emmerzaal, T.L., Wong, S.Y.W., Felgueira, Catarina, Stiers, Kyle M., Kozicz, T., Morava, E., and Ghesquiere, Bart

Abstract

Contains fulltext : 203618.pdf (publisher's version ) (Closed access)

Published
2019

42. Consensus guidelines for the use and interpretation of angiogenesis assays

Author

Nowak-Sliwinska, Patrycja, Alitalo, Kari, Allen, Elizabeth, Anisimov, Andrey, Aplin, Alfred C., Auerbach, Robert, Augustin, Hellmut G., Bates, David O., van Beijnum, Judy R., Bender, R. Hugh F., Bergers, Gabriele, Bikfalvi, Andreas, Bischoff, Joyce, Boeck, Barbara C., Brooks, Peter C., Bussolino, Federico, Cakir, Bertan, Carmeliet, Peter, Castranova, Daniel, Cimpean, Anca M., Cleaver, Ondine, Coukos, George, Davis, George E., De Palma, Michele, Dimberg, Anna, Dings, Ruud P. M., Djonov, Valentin, Dudley, Andrew C., Dufton, Neil P., Fendt, Sarah-Maria, Ferrara, Napoleone, Fruttiger, Marcus, Fukumura, Dai, Ghesquiere, Bart, Gong, Yan, Griffin, Robert J., Harris, Adrian L., Hughes, Christopher C. W., Hultgren, Nan W., Iruela-Arispe, M. Luisa, Irving, Melita, Jain, Rakesh K., Kalluri, Raghu, Kalucka, Joanna, Kerbel, Robert S., Kitajewski, Jan, Klaassen, Ingeborg, Kleinmann, Hynda K., Koolwijk, Pieter, Kuczynski, Elisabeth, Kwak, Brenda R., Marien, Koen, Melero-Martin, Juan M., Munn, Lance L., Nicosia, Roberto F., Noel, Agnes, Nurro, Jussi, Olsson, Anna-Karin, Petrova, Tatiana V., Pietras, Kristian, Pili, Roberto, Pollard, Jeffrey W., Post, Mark J., Quax, Paul H. A., Rabinovich, Gabriel A., Raica, Marius, Randi, Anna M., Ribatti, Domenico, Ruegg, Curzio, Schlingemann, Reinier O., Schulte-Merker, Stefan, Smith, Lois E. H., Song, Jonathan W., Stacker, Steven A., Stalin, Jimmy, Stratman, Amber N., Van de Velde, Maureen, van Hinsbergh, Victor W. M., Vermeulen, Peter B., Waltenberger, Johannes, Weinstein, Brant M., Xin, Hong, Yetkin-Arik, Bahar, Yla-Herttuala, Seppo, Yoder, Mervin C., Griffioen, Arjan W., Nowak-Sliwinska, Patrycja, Alitalo, Kari, Allen, Elizabeth, Anisimov, Andrey, Aplin, Alfred C., Auerbach, Robert, Augustin, Hellmut G., Bates, David O., van Beijnum, Judy R., Bender, R. Hugh F., Bergers, Gabriele, Bikfalvi, Andreas, Bischoff, Joyce, Boeck, Barbara C., Brooks, Peter C., Bussolino, Federico, Cakir, Bertan, Carmeliet, Peter, Castranova, Daniel, Cimpean, Anca M., Cleaver, Ondine, Coukos, George, Davis, George E., De Palma, Michele, Dimberg, Anna, Dings, Ruud P. M., Djonov, Valentin, Dudley, Andrew C., Dufton, Neil P., Fendt, Sarah-Maria, Ferrara, Napoleone, Fruttiger, Marcus, Fukumura, Dai, Ghesquiere, Bart, Gong, Yan, Griffin, Robert J., Harris, Adrian L., Hughes, Christopher C. W., Hultgren, Nan W., Iruela-Arispe, M. Luisa, Irving, Melita, Jain, Rakesh K., Kalluri, Raghu, Kalucka, Joanna, Kerbel, Robert S., Kitajewski, Jan, Klaassen, Ingeborg, Kleinmann, Hynda K., Koolwijk, Pieter, Kuczynski, Elisabeth, Kwak, Brenda R., Marien, Koen, Melero-Martin, Juan M., Munn, Lance L., Nicosia, Roberto F., Noel, Agnes, Nurro, Jussi, Olsson, Anna-Karin, Petrova, Tatiana V., Pietras, Kristian, Pili, Roberto, Pollard, Jeffrey W., Post, Mark J., Quax, Paul H. A., Rabinovich, Gabriel A., Raica, Marius, Randi, Anna M., Ribatti, Domenico, Ruegg, Curzio, Schlingemann, Reinier O., Schulte-Merker, Stefan, Smith, Lois E. H., Song, Jonathan W., Stacker, Steven A., Stalin, Jimmy, Stratman, Amber N., Van de Velde, Maureen, van Hinsbergh, Victor W. M., Vermeulen, Peter B., Waltenberger, Johannes, Weinstein, Brant M., Xin, Hong, Yetkin-Arik, Bahar, Yla-Herttuala, Seppo, Yoder, Mervin C., and Griffioen, Arjan W.

Abstract

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.

Published
2018
Full Text
View/download PDF

43. Codon-specific translation reprogramming promotes resistance to targeted therapy

Author

Rapino, Francesca, Delaunay, Sylvain, Rambow, Florian, Zhou, Zhaoli, Tharun, Lars, De Tullio, Pascal, Sin, Olga, Shostak, Kateryna, Schmitz, Sebastian, Piepers, Jolanda, Ghesquiere, Bart, Karim, Latifa, Charloteaux, Benoit, Jamart, Diane, Florin, Alexandra, Lambert, Charles, Rorive, Andree, Jerusalem, Guy, Leucci, Eleonora, Dewaele, Michael, Vooijs, Marc, Leidel, Sebastian A., Georges, Michel, Voz, Marianne, Peers, Bernard, Buettner, Reinhard, Marine, Jean-Christophe, Chariot, Alain, Close, Pierre, Rapino, Francesca, Delaunay, Sylvain, Rambow, Florian, Zhou, Zhaoli, Tharun, Lars, De Tullio, Pascal, Sin, Olga, Shostak, Kateryna, Schmitz, Sebastian, Piepers, Jolanda, Ghesquiere, Bart, Karim, Latifa, Charloteaux, Benoit, Jamart, Diane, Florin, Alexandra, Lambert, Charles, Rorive, Andree, Jerusalem, Guy, Leucci, Eleonora, Dewaele, Michael, Vooijs, Marc, Leidel, Sebastian A., Georges, Michel, Voz, Marianne, Peers, Bernard, Buettner, Reinhard, Marine, Jean-Christophe, Chariot, Alain, and Close, Pierre

Abstract

Reprogramming of mRNA translation has a key role in cancer development and drug resistance(1). However, the molecular mechanisms that are involved in this process remain poorly understood. Wobble tRNA modifications are required for specific codon decoding during translation(2,3). Here we show, in humans, that the enzymes that catalyse modifications of wobble uridine 34 (U-34) tRNA (U-34 enzymes) are key players of the protein synthesis rewiring that is induced by the transformation driven by the BRAF(V600E) oncogene and by resistance to targeted therapy in melanoma. We show that BRAF(V600E)-expressing melanoma cells are dependent on U34 enzymes for survival, and that concurrent inhibition of MAPK signalling and ELP3 or CTU1 and/or CTU2 synergizes to kill melanoma cells. Activation of the PI3K signalling pathway, one of the most common mechanisms of acquired resistance to MAPK therapeutic agents, markedly increases the expression of U-34 enzymes. Mechanistically, U-34 enzymes promote glycolysis in melanoma cells through the direct, codon-dependent, regulation of the translation of HIF1A mRNA and the maintenance of high levels of HIF1 alpha protein. Therefore, the acquired resistance to anti-BRAF therapy is associated with high levels of U-34 enzymes and HIF1 alpha. Together, these results demonstrate that U-34 enzymes promote the survival and resistance to therapy of melanoma cells by regulating specific mRNA translation.

Published
2018

45. Ischemia-Induced DNA Hypermethylation during Kidney Transplant Predicts Chronic Allograft Injury

Author

Heylen, Line, primary, Thienpont, Bernard, additional, Naesens, Maarten, additional, Busschaert, Pieter, additional, Depreeuw, Jeroen, additional, Smeets, Dominiek, additional, Jochmans, Ina, additional, Monbaliu, Diethard, additional, Pirenne, Jacques, additional, Lerut, Evelyne, additional, Ghesquiere, Bart, additional, Kuypers, Dirk, additional, Lambrechts, Diether, additional, and Sprangers, Ben, additional

Published
2018
Full Text
View/download PDF

46. A roadmap for interpreting (13)C metabolite labeling patterns from cells.

Author

UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, Buescher, Joerg M, Antoniewicz, Maciek R, Boros, Laszlo G, Burgess, Shawn C, Brunengraber, Henri, Clish, Clary B, DeBerardinis, Ralph J, Feron, Olivier, Frezza, Christian, Ghesquiere, Bart, Gottlieb, Eyal, Hiller, Karsten, Jones, Russell G, Kamphorst, Jurre J, Kibbey, Richard G, Kimmelman, Alec C, Locasale, Jason W, Lunt, Sophia Y, Maddocks, Oliver Dk, Malloy, Craig, Metallo, Christian M, Meuillet, Emmanuelle J, Munger, Joshua, Nöh, Katharina, Rabinowitz, Joshua D, Ralser, Markus, Sauer, Uwe, Stephanopoulos, Gregory, St-Pierre, Julie, Tennant, Daniel A, Wittmann, Christoph, Vander Heiden, Matthew G, Vazquez, Alexei, Vousden, Karen, Young, Jamey D, Zamboni, Nicola, Fendt, Sarah-Maria, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, Buescher, Joerg M, Antoniewicz, Maciek R, Boros, Laszlo G, Burgess, Shawn C, Brunengraber, Henri, Clish, Clary B, DeBerardinis, Ralph J, Feron, Olivier, Frezza, Christian, Ghesquiere, Bart, Gottlieb, Eyal, Hiller, Karsten, Jones, Russell G, Kamphorst, Jurre J, Kibbey, Richard G, Kimmelman, Alec C, Locasale, Jason W, Lunt, Sophia Y, Maddocks, Oliver Dk, Malloy, Craig, Metallo, Christian M, Meuillet, Emmanuelle J, Munger, Joshua, Nöh, Katharina, Rabinowitz, Joshua D, Ralser, Markus, Sauer, Uwe, Stephanopoulos, Gregory, St-Pierre, Julie, Tennant, Daniel A, Wittmann, Christoph, Vander Heiden, Matthew G, Vazquez, Alexei, Vousden, Karen, Young, Jamey D, Zamboni, Nicola, and Fendt, Sarah-Maria

Abstract

Measuring intracellular metabolism has increasingly led to important insights in biomedical research. (13)C tracer analysis, although less information-rich than quantitative (13)C flux analysis that requires computational data integration, has been established as a time-efficient method to unravel relative pathway activities, qualitative changes in pathway contributions, and nutrient contributions. Here, we review selected key issues in interpreting (13)C metabolite labeling patterns, with the goal of drawing accurate conclusions from steady state and dynamic stable isotopic tracer experiments.

Published
2015

47. A roadmap for interpreting (13)C metabolite labeling patterns from cells.

Author

Buescher, Joerg M., Antoniewicz, Maciek R., Boros, Laszlo G., Burgess, Shawn C., Brunengraber, Henri, Clish, Clary B., DeBerardinis, Ralph J., Feron, Olivier, Frezza, Christian, Ghesquiere, Bart, Gottlieb, Eyal, Hiller, Karsten, Jones, Russell G., Kamphorst, Jurre J., Kibbey, Richard G., Kimmelman, Alec C., Locasale, Jason W., Lunt, Sophia Y., Maddocks, Oliver D. K., Malloy, Craig, Metallo, Christian M., Meuillet, Emmanuelle J., Munger, Joshua, Noh, Katharina, Rabinowitz, Joshua D., Ralser, Markus, Sauer, Uwe, Stephanopoulos, Gregory, St-Pierre, Julie, Tennant, Daniel A., Wittmann, Christoph, Vander Heiden, Matthew G., Vazquez, Alexei, Vousden, Karen, Young, Jamey D., Zamboni, Nicola, Fendt, Sarah-Maria, Buescher, Joerg M., Antoniewicz, Maciek R., Boros, Laszlo G., Burgess, Shawn C., Brunengraber, Henri, Clish, Clary B., DeBerardinis, Ralph J., Feron, Olivier, Frezza, Christian, Ghesquiere, Bart, Gottlieb, Eyal, Hiller, Karsten, Jones, Russell G., Kamphorst, Jurre J., Kibbey, Richard G., Kimmelman, Alec C., Locasale, Jason W., Lunt, Sophia Y., Maddocks, Oliver D. K., Malloy, Craig, Metallo, Christian M., Meuillet, Emmanuelle J., Munger, Joshua, Noh, Katharina, Rabinowitz, Joshua D., Ralser, Markus, Sauer, Uwe, Stephanopoulos, Gregory, St-Pierre, Julie, Tennant, Daniel A., Wittmann, Christoph, Vander Heiden, Matthew G., Vazquez, Alexei, Vousden, Karen, Young, Jamey D., Zamboni, Nicola, and Fendt, Sarah-Maria

Abstract

Measuring intracellular metabolism has increasingly led to important insights in biomedical research. (13)C tracer analysis, although less information-rich than quantitative (13)C flux analysis that requires computational data integration, has been established as a time-efficient method to unravel relative pathway activities, qualitative changes in pathway contributions, and nutrient contributions. Here, we review selected key issues in interpreting (13)C metabolite labeling patterns, with the goal of drawing accurate conclusions from steady state and dynamic stable isotopic tracer experiments.

Published
2015
Full Text
View/download PDF

48. A roadmap for interpreting 13 C metabolite labeling patterns from cells

Author

Buescher, Joerg M, primary, Antoniewicz, Maciek R, additional, Boros, Laszlo G, additional, Burgess, Shawn C, additional, Brunengraber, Henri, additional, Clish, Clary B, additional, DeBerardinis, Ralph J, additional, Feron, Olivier, additional, Frezza, Christian, additional, Ghesquiere, Bart, additional, Gottlieb, Eyal, additional, Hiller, Karsten, additional, Jones, Russell G, additional, Kamphorst, Jurre J, additional, Kibbey, Richard G, additional, Kimmelman, Alec C, additional, Locasale, Jason W, additional, Lunt, Sophia Y, additional, Maddocks, Oliver DK, additional, Malloy, Craig, additional, Metallo, Christian M, additional, Meuillet, Emmanuelle J, additional, Munger, Joshua, additional, Nöh, Katharina, additional, Rabinowitz, Joshua D, additional, Ralser, Markus, additional, Sauer, Uwe, additional, Stephanopoulos, Gregory, additional, St-Pierre, Julie, additional, Tennant, Daniel A, additional, Wittmann, Christoph, additional, Vander Heiden, Matthew G, additional, Vazquez, Alexei, additional, Vousden, Karen, additional, Young, Jamey D, additional, Zamboni, Nicola, additional, and Fendt, Sarah-Maria, additional

Published
2015
Full Text
View/download PDF

49. Abstract 5057: Activation of stroma-derived matrix metalloproteinases (MMPs) in a model of gastric cancer.

Author

Kandola, Sandhir, primary, Holmberg, Christopher, additional, Ghesquiere, Bart, additional, Impens, Francis, additional, Gevaert, Kris, additional, Kumar, J. Dinesh, additional, Cash, Nicole, additional, Hegyi, Peter, additional, Vlatkovic, Nikolina, additional, Wang, Timothy, additional, Dockray, Graham, additional, and Varro, Andrea, additional

Published
2013
Full Text
View/download PDF

50. Differential roles for the oxygen sensing enzymes PHD1 and PHD3 in the regulation of neutrophil metabolism and function.

Author

Watts E, Willison J, Arienti S, Sadiku P, Coelho P, Sanchez-Garcia M, Zhang A, Murphy F, Dickinson R, Mirchandani A, Morrison T, Lewis A, Vermaelen W, Ghesquiere B, Carmeliet P, Mazzone M, Maxwell P, Pugh C, Dockrell D, Whyte M, and Walmsley S

Abstract

Background: Neutrophils are essential in the early innate immune response to pathogens. Harnessing their antimicrobial powers, without driving excessive and damaging inflammatory responses, represents an attractive therapeutic possibility. The neutrophil population is increasingly recognised to be more diverse and malleable than was previously appreciated. Hypoxic signalling pathways are known to regulate important neutrophil behaviours and, as such, are potential therapeutic targets for regulating neutrophil antimicrobial and inflammatory responses., Methods: We used a combination of in vivo and ex vivo models, utilising neutrophil and myeloid specific PHD1 or PHD3 deficient mouse lines to investigate the roles of oxygen sensing prolyl hydroxylase enzymes in the regulation of neutrophilic inflammation and immunity. Mass spectrometry and Seahorse metabolic flux assays were used to analyse the role of metabolic shifts in driving the downstream phenotypes., Results: We found that PHD1 deficiency drives alterations in neutrophil metabolism and recruitment, in an oxygen dependent fashion. Despite this, PHD1 deficiency did not significantly alter ex vivo neutrophil phenotypes or in vivo outcomes in mouse models of inflammation. Conversely, PHD3 deficiency was found to enhance neutrophil antibacterial properties without excessive inflammatory responses. This was not linked to changes in the abundance of core metabolites but was associated with increased oxygen consumption and increased mitochondrial reactive oxygen species (mROS) production., Conclusions: PHD3 deficiency drives a favourable neutrophil phenotype in infection and, as such, is an important potential therapeutic target., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Watts E et al.)

Published
2024
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results