Leeropdracht
Metabolomics
Benoemingsdatum 01-02-2018
Profiel

Research in the Berkers group focusses on metabolomics: studying the small molecule metabolite profile of cells using mass spectrometry. My group employs a mechanistic metabolomics strategy. By performing metabolic tracer studies using a variety of stable-isotope nutrients and combining such studies with targeted metabolism-oriented proteomics studies, we aim to gain mechanistic insight into cellular metabolism. We apply our metabolomics tools to two biomedical frameworks: metabolism-mediated drug resistance and immuno-metabolism.

 

Metabolism-mediated drug resistance
Metabolic rewiring is increasingly acknowledged to play a role in the sensitivity of cancer cells to anti-cancer therapies. We use metabolomics to find targetable metabolic changes in drug-resistant cells, to study the metabolic mode of action of drugs, or to obtain insight into adverse drug effects. In particular, we investigate proteasome inhibitors, which hold great promise for the treatment of cancer, but are associated with adverse effects and the occurrence of resistance. By characterizing the pathways that cells use to adapt to the action of proteasome inhibitors, we aim to reveal novel therapeutic targets for combination treatment and open up possibilities to treat resistant patients.

 

Immuno-metabolism
Immune responses depend on the balance between two types of T cells: conventional T cells (Tconv), that kill infected or tumor cells, and regulatory T cells (Treg), that inhibit the response of conventional T cells to self- and foreign antigens and are thereby critical to inhibit autoimmunity. Treg and Tconv share many features, including co-stimulatory and cytokine receptors, but differ significantly in their metabolic features. In an Institute for Chemical Immunology project we develop metabolomics strategies to map metabolic differences between these different T cells. Ultimately, we aim to identify metabolic targets that can be exploited to selectively modulate T-cell activity.

Wetenschappelijke expertises
metabolomics
drug profiling
Gegenereerd op 2018-09-19 16:54:39
Curriculum vitae

Celia Berkers studied chemistry at Utrecht University, where she graduated with honours in 2003. She started her PhD at the Harvard Medical School in Boston and continued her research at the Netherlands Cancer Institute in Amsterdam. Berkers received her PhD degree with honors in 2010 and was awarded the Antoni van Leeuwenhoek Prize 2010 for most promising young scientist. She then moved to the Beatson Institute for Cancer Research in Glasgow, where she did a post-doc in the laboratory of Prof. Karen Vousden, supported by a Rubicon fellowship from NWO. In 2013, Dr Berkers joined the Biomolecular Mass Spectrometry and Proteomics Department at Utrecht University as an independent group leader and was awarded a VENI grant from NWO-CW. In 2014, she was awarded the Heineken Young Scientists Award for Biochemistry and Biophysics by the Royal Netherlands Academy of Arts and Sciences. Berkers was appointed full professor at the Faculties of Vetenary Medicine and Science in 2018 and is a member of the Young Academy of the Royal Academy, a group of 50 top young scientists and scholars in the Netherlands.

Gegenereerd op 2018-09-19 16:54:39
Sleutelpublicaties

Leestemaker, Yves, de Jong, Annemieke, Witting, Katharina F, Penning, Renske, Schuurman, Karianne, Rodenko, Boris, Zaal, Esther A, van de Kooij, Bert, Laufer, Stefan, Heck, Albert J R, Borst, Jannie, Scheper, Wiep, Berkers, Celia R & Ovaa, Huib (22-06-2017). Proteasome Activation by Small Molecules. Cell Chemical Biology, 24 (6), (pp. 725-736.e7). Copyright © 2017 Elsevier Ltd. All rights reserved..

Zaal, Esther A, Wu, Wei, Jansen, Gerrit, Zweegman, Sonja, Cloos, Jacqueline & Berkers, Celia R (2017). Bortezomib resistance in multiple myeloma is associated with increased serine synthesis. Cancer & metabolism, 5.

Berkers, Celia R., Maddocks, Oliver D.K., Cheung, Eric C., Mor, Inbal & Vousden, Karen H. (05-11-2013). Metabolic regulation by p53 family members. Cell Metabolism, 18 (5), (pp. 617-633) (17 p.).

Maddocks, Oliver D K, Berkers, Celia R, Mason, Susan M, Zheng, Liang, Blyth, Karen, Gottlieb, Eyal & Vousden, Karen H (24-01-2013). Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature, 493 (7433), (pp. 542-6) (5 p.).

Alle publicaties
  2018
Wu, Wei, Zaal, Esther A, Berkers, Celia R, Lemeer, Simone & Heck, Albert J R (18-04-2018). CTGF/VEGFA-activated fibroblasts promote tumor migration through micro-environmental modulation. Molecular and Cellular Proteomics, 17 (8), (pp. 1502-1514). Published under license by The American Society for Biochemistry and Molecular Biology, Inc..
Oerlemans, Ruud, Berkers, Celia R., Assaraf, Yehuda G, Scheffer, George L, Peters, Godefridus J, Verbrugge, Sue Ellen, Cloos, Jacqueline, Slootstra, Jerry W., Meloen, Rob H., Shoemaker, Robert H., Dijkmans, Ben A C, Scheper, Rik J, Ovaa, Huib & Jansen, Gerrit (14-02-2018). Proteasome inhibition and mechanism of resistance to a synthetic, library-based hexapeptide. Investigational New Drugs, (pp. 1-13) (13 p.).
  2017
Zaal, Esther A, Wu, Wei, Jansen, Gerrit, Zweegman, Sonja, Cloos, Jacqueline & Berkers, Celia R (2017). Bortezomib resistance in multiple myeloma is associated with increased serine synthesis. Cancer & metabolism, 5.
Ruprecht, Benjamin, Zaal, Esther A, Zecha, Jana, Wu, Wei, Berkers, Celia R, Kuster, Bernhard & Lemeer, Simone (15-04-2017). Lapatinib Resistance in Breast Cancer Cells Is Accompanied by Phosphorylation-Mediated Reprogramming of Glycolysis. Cancer Research, 77 (8), (pp. 1842-1853) (12 p.). ©2017 American Association for Cancer Research..
Welle, Thijs, Hoekstra, Anna T., Daemen, Ineke A.J.J.M., Berkers, Celia R. & de Oliveira Costa, Matheus (01-07-2017). Metabolic response of porcine colon explants to in vitro infection by Brachyspira hyodysenteriae - a leap into disease pathophysiology. Metabolomics, 13 (7) (7 p.).
Leestemaker, Yves, de Jong, Annemieke, Witting, Katharina F, Penning, Renske, Schuurman, Karianne, Rodenko, Boris, Zaal, Esther A, van de Kooij, Bert, Laufer, Stefan, Heck, Albert J R, Borst, Jannie, Scheper, Wiep, Berkers, Celia R & Ovaa, Huib (22-06-2017). Proteasome Activation by Small Molecules. Cell Chemical Biology, 24 (6), (pp. 725-736.e7). Copyright © 2017 Elsevier Ltd. All rights reserved..
Widjaja, Christella E., Olvera, Jocelyn G., Metz, Patrick J., Phan, Anthony T., Savas, Jeffrey N., de Bruin, Gerjan, Leestemaker, Yves, Berkers, Celia R., De Jong, Annemieke, Florea, Bogdan I., Fisch, Kathleen, Lopez, Justine, Kim, Stephanie H., Garcia, Daniel A., Searles, Stephen, Bui, Jack D., Chang, Aaron N., Yates, John R, Goldrath, Ananda W., Overkleeft, Hermen S., Ovaa, Huib & Chang, John T. (02-10-2017). Proteasome activity regulates CD8+ T lymphocyte metabolism and fate specification. Journal of Clinical Investigation, 127 (10), (pp. 3609-3623) (15 p.).
Wisse, Lisanne E., Penning, Renske, Zaal, Esther A., van Berkel, Carola G M, ter Braak, Timo J., Polder, Emiel, Kenney, Justin W., Proud, Christopher G, Berkers, Celia R., Altelaar, Maarten A.F., Speijer, Dave, van der Knaap, Marjo S & Abbink, Truus E.M. (20-12-2017). Proteomic and metabolomic analyses of vanishing white matter mouse astrocytes reveal deregulation of ER functions. Frontiers in Cellular Neuroscience, 11 (16 p.).
Loayza-Puch, Fabricio, Rooijers, Koos, Zijlstra, Jelle S., Moumbeini, Behzad, Zaal, Esther A., Oude Vrielink, Joachim F., Lopes, Rui M, Ugalde, Alejandro P., Berkers, Celia R. & Agami, Reuven (01-04-2017). TGFβ1-induced leucine limitation uncovered by differential ribosome codon reading. EMBO Reports, 18 (4), (pp. 549-557) (9 p.).
  2016
Weijer, Ruud, Clavier, Séverine, Zaal, Esther A, Pijls, Maud M E, van Kooten, Robert T, Vermaas, Klaas, Leen, René, Jongejan, Aldo, Moerland, Perry D, van Kampen, Antoine H C, van Kuilenburg, André B P, Berkers, Celia R, Lemeer, Simone & Heger, Michal (01-11-2016). Multi-OMIC profiling of survival and metabolic signaling networks in cells subjected to photodynamic therapy. Cellular and Molecular Life Sciences
Liu, Yao, Garcia Lopes Maia Rodrigues, João, Bonvin, Alexandre M J J, Zaal, Esther A., Berkers, Celia R., Heger, Michal, Gawarecka, Katarzyna, Swiezewska, Ewa, Breukink, Eefjan & Egmond, Maarten R. (15-07-2016). New insight into the catalytic mechanism of bacterial mray from enzyme kinetics and docking studies. Journal of Biological Chemistry, 291 (29), (pp. 15057-15068) (12 p.).
Becher, Isabelle, Werner, Thilo, Doce, Carola, Zaal, Esther A., Tögel, Ina, Khan, Crystal A., Rueger, Anne, Muelbaier, Marcel, Salzer, Elsa, Berkers, Celia R., Fitzpatrick, Paul F., Bantscheff, Marcus & Savitski, Mikhail M. (01-11-2016). Thermal profiling reveals phenylalanine hydroxylase as an off-target of panobinostat. Nature Chemical Biology, 12 (11), (pp. 908-910) (3 p.).
  2015
Berkers, Celia R., De Jong, Annemieke, Schuurman, Karianne G., Linnemann, Carsten, Meiring, Hugo D., Janssen, Lennert, Neefjes, Jacques J., Schumacher, Ton N M, Rodenko, Boris & Ovaa, Huib (01-11-2015). Definition of proteasomal peptide splicing rules for high-efficiency spliced peptide presentation by MHC class I molecules. Journal of Immunology, 195 (9), (pp. 4085-4095) (11 p.).
Berkers, Celia R., De Jong, Annemieke, Schuurman, Karianne G., Linnemann, Carsten, Geenevasen, Jan A J, Schumacher, Ton N M, Rodenko, Boris & Ovaa, Huib (01-11-2015). Peptide splicing in the proteasome creates a novel type of antigen with an isopeptide linkage. Journal of Immunology, 195 (9), (pp. 4075-4084) (10 p.).
  2014
D'Alessandro, Angelo, Amelio, Ivano, Berkers, Celia R, Antonov, Alexey, Vousden, Karen H, Melino, Gerry & Zolla, Lello (15-09-2014). Metabolic effect of TAp63α - enhanced glycolysis and pentose phosphate pathway, resulting in increased antioxidant defense. Oncotarget, 5 (17), (pp. 7722-7733) (12 p.).
  2013
Gao, Y., Koppen, A., Rakhshandehroo, M., Tasdelen, I., van de Graaf, S.F.J., van Loosdregt, J., van Beekum, O., Hamers, N., van Leenen, D., Berkers, C.R., Berger, R., Holstege, F.C.P., Coffer, P.J, Brenkman, A.B., Ovaa, H. & Kalkhoven, E. (2013). Early adipogenesis is regulated through USP7-mediated deubiquitination of the histone acetyltransferase TIP60. Nature Communications, 4, (pp. 2656) (1 p.).
Berkers, Celia R., Maddocks, Oliver D.K., Cheung, Eric C., Mor, Inbal & Vousden, Karen H. (05-11-2013). Metabolic regulation by p53 family members. Cell Metabolism, 18 (5), (pp. 617-633) (17 p.).
Maddocks, Oliver D K, Berkers, Celia R, Mason, Susan M, Zheng, Liang, Blyth, Karen, Gottlieb, Eyal & Vousden, Karen H (24-01-2013). Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature, 493 (7433), (pp. 542-6) (5 p.).
van Loosdregt, J., Fleskens, V., Fu, J., Brenkman, A.B., Bekker, C.P.J., Pals, C.E.G.M., Meerding, J.M., Berkers, C.R., Barbi, J., Grone, A., Sijts, E.J.A.M., Maurice, M.M., Kalkhoven, E., Prakken, A.B.J., Ovaa, H., Pan, F., Zaiss, D.M.W. & Coffer, P.J (2013). Stabilization of the transcription factor Foxp3 by the deubiquitinase USP7 increases Treg-cell-suppressive capacity. Immunity, 39 (2), (pp. 259-271) (13 p.).
  2012
De Jong, Annemieke, Schuurman, Karianne G., Rodenko, Boris, Ovaa, Huib & Berkers, Celia R. (29-01-2012). Fluorescence-based proteasome activity profiling. (22 p.). Humana Press.
Berkers, Celia R., Leestemaker, Yves, Schuurman, Karianne G., Ruggeri, Bruce, Jones-Bolin, Susan, Williams, Michael & Ovaa, Huib (07-05-2012). Probing the specificity and activity profiles of the proteasome inhibitors bortezomib and delanzomib. Molecular Pharmaceutics, 9 (5), (pp. 1126-1135) (10 p.).
  2011
Nijholt, D A T, de Graaf, T R, van Haastert, E S, Oliveira, A Osório, Berkers, C R, Zwart, R, Ovaa, H, Baas, F, Hoozemans, J J M & Scheper, W (2011). Endoplasmic reticulum stress activates autophagy but not the proteasome in neuronal cells - implications for Alzheimer's disease. Cell Death and Differentiation, 18 (6), (pp. 1071-81) (11 p.).
Potts, B C, Albitar, M X, Anderson, K C, Baritaki, S, Berkers, C, Bonavida, B, Chandra, J, Chauhan, D, Cusack, J C, Fenical, W, Ghobrial, I M, Groll, M, Jensen, P R, Lam, K S, Lloyd, G K, McBride, W, McConkey, D J, Miller, C P, Neuteboom, S T C, Oki, Y, Ovaa, H, Pajonk, F, Richardson, P G, Roccaro, A M, Sloss, C M, Spear, M A, Valashi, E, Younes, A & Palladino, M A (2011). Marizomib, a proteasome inhibitor for all seasons - preclinical profile and a framework for clinical trials. Curr Cancer Drug Targets, 11 (3), (pp. 254-84) (31 p.).
  2010
Berkers, Celia R & Ovaa, Huib (2010). Drug discovery and assay development in the ubiquitin-proteasome system. Biochemical Society Transactions, 38 (Pt 1), (pp. 14-20) (7 p.).
Pelletier, S., Schuurman, K.G., Berkers, C.R., Ovaa, H., Heck, A.J.R. & Raijmakers, R. (2010). Quantifying cross-tissue diversity in proteasome complexes by mass spectrometry. Molecular BioSystems, 6, (pp. 1450-1453) (4 p.).
  2009
Middeldorp, Jinte, Kamphuis, Willem, Sluijs, Jacqueline A, Achoui, Dalila, Leenaars, Cathalijn, Feenstra, Matthijs G P, van Tijn, Paula, Fischer, David F, Berkers, Celia, Ovaa, Huib, Quinlan, Roy A & Hol, Elly M (2009). Intermediate filament transcription in astrocytes is repressed by proteasome inhibition. FASEB Journal, 23 (8), (pp. 2710-26) (17 p.).
Berkers, Celia R, de Jong, Annemieke, Ovaa, Huib & Rodenko, Boris (2009). Transpeptidation and reverse proteolysis and their consequences for immunity. International Journal of Biochemistry and Cell Biology, 41 (1), (pp. 66-71) (6 p.).
  2008
Raijmakers, R., Berkers, C.R., de Jong, G.J., Ovaa, H., Heck, A.J.R. & Mohammed, S. (2008). Automated online sequential isotope labeling for protein quantitation applied to proteasome tissue specific diversity. Molecular and Cellular Proteomics, 7, (pp. 1755-1762) (8 p.).
Piva, Roberto, Ruggeri, Bruce, Williams, Michael, Costa, Giulia, Tamagno, Ilaria, Ferrero, Dario, Giai, Valentina, Coscia, Marta, Peola, Silvia, Massaia, Massimo, Pezzoni, Gabriella, Allievi, Cecilia, Pescalli, Nicoletta, Cassin, Mara, di Giovine, Stefano, Nicoli, Paola, de Feudis, Paola, Strepponi, Ivan, Roato, Ilaria, Ferracini, Riccardo, Bussolati, Benedetta, Camussi, Giovanni, Jones-Bolin, Susan, Hunter, Kathryn, Zhao, Hugh, Neri, Antonino, Palumbo, Antonio, Berkers, Celia, Ovaa, Huib, Bernareggi, Alberto & Inghirami, Giorgio (2008). CEP-18770 - A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib. Blood, 111 (5), (pp. 2765-75) (11 p.).
Bakker, Arnold H., Hoppes, Rieuwert, Linnemann, Carsten, Toebes, Mireille, Rodenko, Boris, Berkers, Celia R., Hadrup, Sine Reker, Van Esch, Wim J. E., Heemskerk, Mirjam H. M., Ovaa, Huib & Schumacher, Ton N M (25-03-2008). Conditional MHC class I ligands and peptide exchange technology for the human MHC gene products HLA-A1, -A3, -A11, and -B7. Proceedings of the National Academy of Sciences of the United States of America, 105 (10), (pp. 3825-3830) (6 p.).
Oerlemans, Ruud, Franke, Niels E, Assaraf, Yehuda G, Cloos, Jacqueline, van Zantwijk, Ina, Berkers, Celia R, Scheffer, George L, Debipersad, Kabir, Vojtekova, Katharina, Lemos, Clara, van der Heijden, Joost W, Ylstra, Bauke, Peters, Godefridus J, Kaspers, Gertjan L, Dijkmans, Ben A C, Scheper, Rik J & Jansen, Gerrit (15-09-2008). Molecular basis of bortezomib resistance - proteasome subunit beta5 (PSMB5) gene mutation and overexpression of PSMB5 protein. Blood, 112 (6), (pp. 2489-99) (11 p.).
  2007
Kraus, M, Rückrich, T, Reich, M, Gogel, J, Beck, A, Kammer, W, Berkers, C R, Burg, D, Overkleeft, H, Ovaa, H & Driessen, C (2007). Activity patterns of proteasome subunits reflect bortezomib sensitivity of hematologic malignancies and are variable in primary human leukemia cells. Leukemia, 21 (1), (pp. 84-92) (9 p.).
Berkers, Celia R, van Leeuwen, Fijs W B, Groothuis, Tom A, Peperzak, Victor, van Tilburg, Erica W, Borst, Jannie, Neefjes, Jacques J & Ovaa, Huib (22-08-2007). Profiling proteasome activity in tissue with fluorescent probes. Molecular Pharmaceutics, 4 (5), (pp. 739-48) (10 p.).
  2006
Verdoes, Martijn, Florea, Bogdan I, Menendez-Benito, Victoria, Maynard, Christa J, Witte, Martin D, van der Linden, Wouter A, van den Nieuwendijk, Adrianus M C H, Hofmann, Tanja, Berkers, Celia R, van Leeuwen, Fijs W B, Groothuis, Tom A, Leeuwenburgh, Michiel A, Ovaa, Huib, Neefjes, Jacques J, Filippov, Dmitri V, van der Marel, Gijs A, Dantuma, Nico P & Overkleeft, Herman S (2006). A fluorescent broad-spectrum proteasome inhibitor for labeling proteasomes in vitro and in vivo. Chemistry and Biology, 13 (11), (pp. 1217-26) (10 p.).
Verdoes, Martijn, Berkers, Celia R, Florea, Bogdan I., van Swieten, Paul F, Overkleeft, Herman S. & Ovaa, Huib (01-01-2006). Chemical proteomics profiling of proteasome activity. Methods in Molecular Biology, 328, (pp. 51-69) (19 p.).
Groll, Michael, Berkers, Celia R, Ploegh, Hidde L & Ovaa, Huib (2006). Crystal structure of the boronic acid-based proteasome inhibitor bortezomib in complex with the yeast 20S proteasome. Structure with Folding & design, 14 (3), (pp. 451-6) (6 p.).
Risseeuw, Martijn D.P., Berkers, Celia R., Ploegh, Hidde L. & Ovaa, Huib (29-05-2006). Synthesis of tritium labeled KRN7000. Tetrahedron Letters, 47 (22), (pp. 3677-3679) (3 p.).
  2005
Chauhan, Dharminder, Catley, Laurence, Li, Guilan, Podar, Klaus, Hideshima, Teru, Velankar, Mugdha, Mitsiades, Constantine, Mitsiades, Nicolas, Yasui, Hiroshi, Letai, Anthony, Ovaa, Huib, Berkers, Celia, Nicholson, Benjamin, Chao, Ta-Hsiang, Neuteboom, Saskia T C, Richardson, Paul, Palladino, Michael A & Anderson, Kenneth C (2005). A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib. Cancer Cell, 8 (5), (pp. 407-19) (13 p.).
Berkers, Celia R, Verdoes, Martijn, Lichtman, Eben, Fiebiger, Edda, Kessler, Benedikt M, Anderson, Kenneth C, Ploegh, Hidde L, Ovaa, Huib & Galardy, Paul J (2005). Activity probe for in vivo profiling of the specificity of proteasome inhibitor bortezomib. Nature Methods, 2 (5), (pp. 357-62) (6 p.).
Berkers, Celia R & Ovaa, Huib (2005). Immunotherapeutic potential for ceramide-based activators of iNKT cells. Trends in Pharmacological Sciences, 26 (5), (pp. 252-7) (6 p.).
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Gegenereerd op 2018-09-19 16:54:39
Project:
Institute for Chemical Immunology
01-01-2014 tot 31-12-2023
Algemene projectbeschrijving 

The Institute for Chemical Immunlogy is an NWO Gravitation project coordinator by Leiden University. It will define and exploit a new field termed chemical immunology and train a novel generation of interdisciplinary scientists. It aims to promote academic excellence; with economic and clinical translation of new treatment options for a large population of patients that currently only have limited treatment options.

Rol: Uitvoerder Financiering
1e geldstroom
Projectleden
Overige projectleden:
  • prof. dr. Sjaak Neefjes (NKI; coordinator)
  • prof. dr. Hermen Overkleeft (LU)
  • prof. dr. Carl Figdor (RU)
  • prof. dr. Ton Schumacher (NKI)

Gegenereerd op 2018-09-19 16:54:39
Volledige naam
prof. dr. C.R. Berkers Contactgegevens
Nieuw Gildestein

Yalelaan 2
Kamer 243
3584 CM  UTRECHT

Telefoonnummer direct 030 253 5381
Hugo R. Kruytgebouw

Padualaan 8
Kamer O601
3584 CH  UTRECHT

Telefoonnummer direct 030 253 9183
Gegenereerd op 2018-09-19 16:54:39
Laatst bijgewerkt op 12-04-2018