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1. 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

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

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

Author

Buescher, Joerg M, 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, Buescher, Joerg M, 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

17. 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

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

Author

Buescher, Joerg M, 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, Buescher, Joerg M, 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

19. 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

20. 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

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