PhD T.B.M. Hakvoort publications

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Publications PhD T.B.M. Hakvoort

Position
Research Associate
Main activities
Education, Research
Specialisation
Biochemistry, molecular biology,in vivo metabolism with stable isotopes
Focus of research

Proteins turn over continuously. Protein breakdown generates toxic ammonia. Glutamine and urea synthesis are the main pathways for ammonia detoxification, but their mutual dependence is still not sorted out. A ~5% reduction in urea synthesis causes lethal hyperammonemia, but a 35% reduction in glutamine synthesis produces no phenotype, even though glutamine synthetase is, thus far, held responsible for preventing hyperammonemia. Using tissue-specific knockout mice and stable isotope-based fluxomics, we investigate the interorgan dependence and (patho )physiological determinants of glutamine and urea synthesis, and the requirement of glutamine synthesis for urea synthesis. Environmental conditions that are studied include high-protein diets (high-protein diets are satiating and facilitate weight reduction), fasting (a proxy for cachexia), and intestinal bacterial overgrowth and acidosis (the encephalopathy-provoking condition in cirrhotic patients).

2019

  • Kruepunga Nutmethee, Hakvoort Theodorus B. M., Hikspoors Jill P. J. M., Köhler S. Eleonore, Lamers Wouter H. Anatomy of rodent and human livers: What are the differences? BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE 2019;1865 (5):869-878 [PubMed]
  • Hakvoort Theodorus B. M., Lamers Wouter H. Reply Hepatology (Baltimore, Md.) 2019;69 (2):922-923 [PubMed]

2018

  • Meijer Bartolomeus J., Wielenga Mattheus C. B., Hoyer Patricia B., Amos-Landgraf James M., Hakvoort Theodorus B. M., Muncan Vanesa, Heijmans Jarom, van den Brink Gijs R. Colorectal tumor prevention by the progestin medroxyprogesterone acetate is critically dependent on postmenopausal status Oncotarget 2018;9 (55):30561-30567 [PubMed]
  • Chennupati Ramesh, Meens Merlijn J., Janssen Ben J., van Dijk Paul, Hakvoort Theodorus B. M., Lamers Wouter H., de Mey Jo G. R., Koehler S. Eleonore Deletion of endothelial arginase 1 does not improve vasomotor function in diabetic mice Physiological reports 2018;6 (11) [PubMed]
  • Botschuijver S., Welting O., Levin E., Maria-Ferreira D., Koch E., Montijn R. C., Seppen J., Hakvoort T. B. M., Schuren F. H. J., de Jonge W. J., van den Wijngaard R. M. Reversal of visceral hypersensitivity in rat by Menthacarin , a proprietary combination of essential oils from peppermint and caraway, coincides with mycobiome modulation Neurogastroenterology and motility 2018;30 (6):e13299 [PubMed]

2017

  • Wildenberg Manon E., Levin Alon D., Ceroni Alessandro, Guo Zhen, Koelink Pim J., Hakvoort Theodorus B. M., Westera Liset, Bloemendaal Felicia M., Brandse Johannan F., Simmons Alison, D'Haens Geert R., Ebner Daniel, van den Brink Gijs R. Benzimidazoles Promote Anti-TNF Mediated Induction of Regulatory Macrophages and Enhance Therapeutic Efficacy in a Murine Model Journal of Crohn s & colitis 2017;11 (12):1480-1490 [PubMed]
  • Zhao Jing Gene-expression profiling to reveal pathogenic mechanisms in disease 2017. 163p. ISBN 9789462997202. [UvA Dissertations Online] University of Amsterdam. (Supervisor: de Jonge W. J.; Co-supervisors: Lamers W. H., Hakvoort T. B. M.)
  • Hakvoort Theodorus B. M., He Youji, van Herk Irene, Vermeulen Jacqueline L. M., Ruijter Jan, Lamers Wouter H. Intestinal glutamine synthetase colocalizes with goblet cells and decreases enterocyte proliferationin: Dominique Meynial-Denis, editors. Glutamine. Boca Raton: Taylor & Francis; 2017. p. 21
  • Zhao Jing, Hakvoort Theodorus B. M., Ruijter Jan M., Jongejan Aldo, Koster Jan, Swagemakers Sigrid M. A., Sokolovic Aleksandar, Lamers Wouter H. Maternal diabetes causes developmental delay and death in early-somite mouse embryos Scientific reports 2017;7 (1):11714 [PubMed]
  • Hakvoort Theodorus B. M., He Youji, Kulik Wim, Vermeulen Jacqueline L. M., Duijst Suzanne, Ruijter Jan M., Runge Jurgen H., Deutz Nicolaas E. P., Koehler S. Eleonore, Lamers Wouter H. Pivotal Role of Glutamine Synthetase in Ammonia Detoxification Hepatology (Baltimore, Md.) 2017;65 (1):281-293 [PubMed]
  • Doorenspleet M. E., Westera L., Peters C. P., Hakvoort T. B. M., Esveldt R. E., Vogels E., van Kampen A. H. C., Baas F., Buskens C., Bemelman W. A., D'Haens G., Ponsioen C. Y., te Velde A. A., de Vries N. [=Niek], van den Brink G. R. Profoundly Expanded T-cell Clones in the Inflamed and Uninflamed Intestine of Patients With Crohn's Disease Journal of Crohn s & colitis 2017;11 (7):831-839 [PubMed]
  • Zhao J., Hakvoort T. B. M., Jongejan A., Ruijter J. M., van Kampen A. H. C., Lamers W. H. Unexpected regulation of miRNA abundance during adaptation of early-somite mouse embryos to diabetic pregnancy Biochemical and biophysical research communications 2017;482 (4):1013-1018 [PubMed]

2016

  • Zhao Jing, Hakvoort Theodorus B. M., Willemsen A. Marcel, Jongejan Aldo, Sokolovic Milka, Bradley Edward J., de Boer Vincent C. J., Baas Frank, van Kampen Antoine H. C., Lamers Wouter H. Effect of Hyperglycemia on Gene Expression during Early Organogenesis in Mice PLoS ONE 2016;11 (7):e0158035 [PubMed]
  • van Wenum Martien, Adam Aziza A. A., Hakvoort Theodorus B. M., Hendriks Erik J., Shevchenko Valery, van Gulik Thomas M., Chamuleau Robert A. F. M., Hoekstra Ruurdtje Selecting Cells for Bioartificial Liver Devices and the Importance of a 3D Culture Environment: A Functional Comparison between the HepaRG and C3A Cell Lines International journal of biological sciences 2016;12 (8):964-978 [PubMed]

2014

  • Zuurbier Coert J., Heinen Andre, Koeman Anneke, Stuifbergen Roy, Hakvoort Theodorus B. M., Weber Nina C., Hollmann Markus W. Cardioprotective efficacy depends critically on pharmacological dose, duration of ischaemia, health status of animals and choice of anaesthetic regimen: a case study with folic acid Journal of translational medicine 2014;12 (1):325 [PubMed]
  • Falix Farah A., Weeda Víola B., Labruyere Wilhelmina T., Poncy Alexis, de Waart Dirk R., Hakvoort Theodorus B. M., Lemaigre Frédéric, Gaemers Ingrid C., Aronson Daniël C., Lamers Wouter H. Hepatic Notch2 deficiency leads to bile duct agenesis perinatally and secondary bile duct formation after weaning Developmental biology 2014;396 (2):201-213 [PubMed]
  • Runge Jurgen H., Bakker Pieter J., Gaemers Ingrid C., Verheij Joanne, Hakvoort Theo B. M., Ottenhoff Roelof, Nederveen Aart J., Stoker Jaap Measuring liver triglyceride content in mice: non-invasive magnetic resonance methods as an alternative to histopathology Magma (New York, N.Y.) 2014;27 (4):317-327 [PubMed]
  • Runge Jurgen H., Bakker Pieter J., Gaemers Ingrid C., Verheij Joanne, Hakvoort Theo B. M., Ottenhoff Roelof, Stoker Jaap, Nederveen Aart J. Quantitative determination of liver triglyceride levels with 3T ¹H-MR spectroscopy in mice with moderately elevated liver fat content Academic radiology 2014;21 (11):1446-1454 [PubMed]

2013

  • Cloots Roy H. E., Sankaranarayanan Selvakumari, de Theije Chiel C., Poynter Matthew E., Terwindt Els, van Dijk Paul, Hakvoort Theodorus B. M., Lamers Wouter H., Köhler S. Eleonore Ablation of Arg1 in hematopoietic cells improves respiratory function of lung parenchyma, but not that of larger airways or inflammation in asthmatic mice American journal of physiology. Lung cellular and molecular physiology 2013;305 (5):L364-L376 [PubMed]
  • Nibourg Geert A. A., Hoekstra Ruurdtje, van der Hoeven Tessa V., Ackermans Mariette T., Hakvoort Theodorus B. M., van Gulik Thomas M., Chamuleau Robert A. F. M. Effects of acute-liver-failure-plasma exposure on hepatic functionality of HepaRG-AMC-bioartificial liver Liver international 2013;33 (4):516-524 [PubMed]
  • Marion Vincent, Sankaranarayanan Selvakumari, de Theije Chiel, van Dijk Paul, Hakvoort Theo B. M., Lamers Wouter H., Köhler Eleonore S. Hepatic adaptation compensates inactivation of intestinal arginine biosynthesis in suckling mice PLoS ONE 2013;8 (6):e67021 [PubMed]
  • Nibourg Geert A. A., Hoekstra Ruurdtje, van der Hoeven Tessa V., Ackermans Mariëtte T., Hakvoort Theodorus B. M., van Gulik Thomas M., Chamuleau Robert A. F. M. Increased hepatic functionality of the human hepatoma cell line HepaRG cultured in the AMC bioreactor international journal of biochemistry & cell biology 2013;45 (8):1860-1868 [PubMed]
  • Garcia-Caraballo Sonia C., Comhair Tine M., Verheyen Fons, Gaemers Ingrid, Schaap Frank G., Houten Sander M., Hakvoort Theodorus B. M., Dejong Cornelis H. C., Lamers Wouter H., Koehler S. Eleonore Prevention and reversal of hepatic steatosis with a high-protein diet in mice BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE 2013;1832 (5):685-695 [PubMed]

2012

  • Mockel Anais, Obringer Cathy, Hakvoort Theodorus B. M., Seeliger Mathias, Lamers Wouter H., Stoetzel Corinne, Dollfus Hélène, Marion Vincent Pharmacological Modulation of the Retinal Unfolded Protein Response in Bardet-Biedl Syndrome Reduces Apoptosis and Preserves Light Detection Ability Journal of biological chemistry 2012;287 (44):37483-37494 [PubMed]
  • Hoekstra Ruurdtje, Nibourg Geert A. A., van der Hoeven Tessa V., Ackermans Mariëtte T., Hakvoort Theodorus B. M., van Gulik Thomas M., Oude Elferink Ronald P., Chamuleau Robert A. F. M. The effect of rat acute-liver-failure plasma on HepaRG cells International journal of artificial organs 2012;35 (11):1006-1014 [PubMed]

2011

  • Hakvoort Theodorus B. M., Moerland Perry D., Frijters Raoul, Sokolovic Aleksandar, Labruyere Wilhelmina T., Vermeulen Jacqueline L. M., Ver Loren van Themaat Emiel, Breit Timo M., Wittink Floyd R. A., van Kampen Antoine H. C., Verhoeven Arthur J., Lamers Wouter H., Sokolovic Milka Interorgan Coordination of the Murine Adaptive Response to Fasting Journal of biological chemistry 2011;286 (18):16332-16343 [PubMed]
  • Hoekstra Ruurdtje, Nibourg Geert A. A., van der Hoeven Tessa V., Ackermans Mariëtte T., Hakvoort Theodorus B. M., van Gulik Thomas M., Lamers Wouter H., Elferink Ronald P. Oude, Chamuleau Robert A. F. M. The HepaRG cell line is suitable for bioartificial liver application international journal of biochemistry & cell biology 2011;43 (10):1483-1489 [PubMed]

2010

  • He Youji, Hakvoort Theodorus B. M., Vermeulen Jacqueline L. M., Labruyère Wilhelmina T., de Waart D. Rudi, van der Hel W. Saskia, Ruijter Jan M., Uylings Harry B. M., Lamers Wouter H. Glutamine Synthetase Deficiency in Murine Astrocytes Results in Neonatal Death Glia 2010;58 (6):741-754 [PubMed]
  • He Youji, Hakvoort Theodorus B. M., Köhler S. Eleonore, Vermeulen Jacqueline L. M., de Waart D. Rudi, de Theije Chiel, ten Have Gabrie A. M., van Eijk Hans M. H., Kunne Cindy, Labruyere Wilhelmina T., Houten Sander M., Sokolovic Milka, Ruijter Jan M., Deutz Nicolaas E. P., Lamers Wouter H. Glutamine Synthetase in Muscle Is Required for Glutamine Production during Fasting and Extrahepatic Ammonia Detoxification Journal of biological chemistry 2010;285 (13):9516-9524 [PubMed]
  • Sokolović Milka, Sokolović Aleksandar, van Roomen Cindy P. A. A., Gruber Anna, Ottenhoff Roelof, Scheij Saskia, Hakvoort Theodorus B. M., Lamers Wouter H., Groen Albert K. Unexpected effects of fasting on murine lipid homeostasis - Transcriptomic and lipid profiling Journal of hepatology 2010;52 (5):737-744 [PubMed]

2009

  • van Gassen K. L. I., van der Hel W. S., Hakvoort T. B. M., Lamers W. H., de Graan P. N. E. Haploinsufficiency of glutamine synthetase increases susceptibility to experimental febrile seizures Genes, brain, and behavior 2009;8 (3):290-295 [PubMed]

2008

  • Poyck Paul P. C., Hoekstra Ruurdtje, Vermeulen Jacqueline L. M., van Wijk Albert C. W. A., Chamuleau Robert A. F. M., Hakvoort Theodorus B. M., van Gulik Thomas M., Lamers Wouter H. Expression of glutamine synthetase and carbamoylphosphate synthetase i in a bioartificial liver: markers for the development of zonation in vitro Cells, tissues, organs 2008;188 (3):259-269 [PubMed]
  • Sokolović Milka The transcriptomic signature of fasting 2008. 175p. ISBN 9789090231389. [UvA Dissertations Online] University of Amsterdam. (Supervisor: Lamers W. H.; Co-supervisor: Hakvoort T. B. M.)
  • Sokolović Milka, Sokolović Aleksandar, Wehkamp Diederik, Ver Loren van Themaat Emiel, de Waart Dirk R., Gilhuijs-Pederson Lisa A., Nikolsky Yuri, van Kampen Antoine H. C., Hakvoort Theodorus B. M., Lamers Wouter H. The transcriptomic signature of fasting murine liver BMC genomics 2008;9 (1):528 [PubMed]

2007

  • He Youji Effects of tissue-specific inactivitation of glutamine synthetase in the mouse 2007. 142p. ISBN 9789090223599. [UvA Dissertations Online] University of Amsterdam. (Supervisor: Lamers Wout H.; Co-supervisor: Hakvoort Theodorus B. M.)
  • Sokolović Milka, Wehkamp Diederik, Sokolović Aleksandar, Vermeulen Jacqueline, Gilhuijs-Pederson Lisa A., van Haaften Rachel I. M., Nikolsky Yuri, Evelo Chris T. A., van Kampen Antoine H. C., Hakvoort Theodorus B. M., Lamers Wouter H. Fasting induces a biphasic adaptive metabolic response in murine small intestine BMC genomics 2007;8 (1):361 [PubMed]
  • He Youji, Hakvoort Theodorus B. M., Vermeulen Jacqueline L. M., Lamers Wouter H., van Roon Maria A. Glutamine synthetase is essential in early mouse embryogenesis Developmental dynamics 2007;236 (7):1865-1875 [PubMed]
  • Stanulović Vesna S., Kyrmizi Irene, Kruithof-de Julio Marianna, Hoogenkamp Maarten, Vermeulen Jacqueline L. M., Ruijter Jan M., Talianidis Iannis, Hakvoort Theodorus B. M., Lamers Wouter H. Hepatic HNF4alpha deficiency induces periportal expression of glutamine synthetase and other pericentral enzymes Hepatology (Baltimore, Md.) 2007;45 (2):433-444 [PubMed]
  • Stanulovic Vesna S. Regulation of the glutamine synthetase gene expression in the liver 2007. 141p. ISBN 9789090224442. [UvA Dissertations Online] University of Amsterdam. (Supervisor: Lamers Wouter H.; Co-supervisor: Hakvoort Theodorus B. M.)
  • Hakvoort Theodorus B. M., Vermeulen Jacqueline L. M., Lamers Wouter H. STAT5 deficiency does not affect the expression of glutamine synthetase in mouse liver Hepatology (Baltimore, Md.) 2007;45 (4):1082; author reply 1083 [PubMed]

2006

  • van Straaten Henny W. M., He Youji, van Duist Marjan M., Labruyère Wil T., Vermeulen Jacqueline L. M., van Dijk Paul J., Ruijter Jan M., Lamers Wouter H., Hakvoort Theodorus B. M. Cellular concentrations of glutamine synthetase in murine organs Biochemistry and cell biology = Biochimie et biologie cellulaire 2006;84 (2):215-231 [PubMed]
  • Stanulović V. S., Garcia de Veas Lovillo R. M., Labruyère W. T., Ruijter J. M., Hakvoort T. B. M., Lamers W. H. The 3'-UTR of the glutamine-synthetase gene interacts specifically with upstream regulatory elements, contains mRNA-instability elements and is involved in glutamine sensing Biochimie 2006;88 (9):1255-1264 [PubMed]

2005

  • Heideman Daniëlle A. M., Overmeer Renée M., van Beusechem Victor W., Lamers Wouter H., Hakvoort Theodorus B. M., Snijders Peter J. F., Craanen Mikael E., Offerhaus G. Johan A., Meijer Chris J. L. M., Gerritsen Winald R. Inhibition of angiogenesis and HGF-cMET-elicited malignant processes in human hepatocellular carcinoma cells using adenoviral vector-mediated NK4 gene therapy Cancer gene therapy 2005;12 (12):954-962 [PubMed]
  • Kruithof-de Julio Marianna, Labruyère Wilhelmina T., Ruijter Jan M., Vermeulen Jacqueline L. M., Stanulović Vesna, Stallen Jan M. P., Baldysiak-Figiel Alicja, Gebhardt Rolf, Lamers Wouter H., Hakvoort Theodorus B. M. The RL-ET-14 cell line mediates expression of glutamine synthetase through the upstream enhancer/promoter region Journal of hepatology 2005;43 (1):126-131 [PubMed]

2004

  • Ovejero Christine, Cavard Catherine, Périanin Axel, Hakvoort Theodorus, Vermeulen Jacqueline, Godard Cécile, Fabre Monique, Chafey Philippe, Suzuki Kazuo, Romagnolo Béatrice, Yamagoe Satoshi, Perret Christine Identification of the leukocyte cell-derived chemotaxin 2 as a direct target gene of beta-catenin in the liver Hepatology (Baltimore, Md.) 2004;40 (1):167-176 [PubMed]
  • de Julio M. Signal-transduction pathways inducing a pericentral phenotype in hepatocytes 2004. 126p. ISBN 9789090183930. [UvA Dissertations Online] University of Amsterdam. (Supervisor: Lamers W. H.; Co-supervisors: Hakvoort T. B. M., Perret C.)

2003

  • Garcia de Veas Lovillo Rocio M., Ruijter Jan M., Labruyère Wil T., Hakvoort Theodorus B. M., Lamers Wouter H. Upstream and intronic regulatory sequences interact in the activation of the glutamine synthetase promoter European Journal of Biochemistry / FEBS 2003;270 (2):206-212 [PubMed]

2002

  • Meije Clifton B., Hakvoort Theodorus B. M., Swart Guido W. M., Westerhof Wiete, Lamers Wouter H., Das Pranab K. Gene expression patterns in melanocytic cells: candidate markers for early stage and malignant transformation Journal of pathology 2002;196 (1):51-58 [PubMed]
  • Meije Clifton B., Das Pranab K., Jans Miranda M. E., Hau Chi, van der Wal Allard C., Alders Marielle, Hakvoort Theodorus B. M., Weidle Ulrich H., Lamers Wouter H., Swart Guido W. M. Multiple complementary transcripts of pCMa1, a novel gene located at chromosome 11p15.1-2, and melanocytic cell transformation Journal of pathology 2002;197 (5):668-676 [PubMed]

2001

  • Spijkers J. A., van den Hoff M. J., Hakvoort T. B., Vermeulen J. L., Tesink-Taekema S., Lamers W. H. Foetal rise in hepatic enzymes follows decline in c-met and hepatocyte growth factor expression Journal of hepatology 2001;34 (5):699-710 [PubMed]

2000

  • Assay for the isolation of hepatogenic factors. Key molecules in hepatocyte formation and liver morphogenesis Methods in molecular biology (Clifton, N.J.) 2000;136:87-100 [PubMed]

1999

  • Expression pattern of glutamine synthetase marks transition from collecting into conducting hepatic veins journal of histochemistry and cytochemistry 1999;47 (12):1507-1512 [PubMed]

1998

  • Regulation of the spatiotemporal pattern of expression of the glutamine synthetase gene Progress in nucleic acid research and molecular biology 1998;61:243-308 [PubMed]

1996

  • Isolation of up- and down-regulated cDNAs associated with hepatocellular carcinoma by a subtraction-enhanced display technique BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE 1996;1315 (3):169-175 [PubMed]
  • Preparation of a differentially expressed, full-length cDNA expression library by RecA-mediated triple-strand formation with subtractively enriched cDNA fragments Nucleic acids research 1996;24 (17):3478-3480 [PubMed]

1994

  • Identification of enriched sequences from a cDNA subtraction-hybridization procedure Nucleic acids research 1994;22 (5):878-879 [PubMed]

1990

  • Amino acid sequence requirements for the association of apocytochrome c with mitochondria Proceedings of the National Academy of Sciences of the United States of America 1990;87 (15):5729-5733 [PubMed]
  • Reversible import of apocytochrome c into mitochondria Proceedings of the National Academy of Sciences of the United States of America 1990;87 (13):4996-5000 [PubMed]

1988

  • Cytochrome c oxidase: organ-specific isoenzymes and deficiencies Journal of inherited metabolic disease 1988;11 (Suppl. 2):202-204 [PubMed]

1987

  • Bovine cytochrome c oxidases, purified from heart, skeletal muscle, liver and kidney, differ in the small subunits but show the same reaction kinetics with cytochrome c BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS 1987;893 (2):251-258 [PubMed]
  • Human cytochrome c oxidase isoenzymes from heart and skeletal muscle; purification and properties BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS 1987;890 (2):144-150 [PubMed]

1985

  • Identification of denatured enzyme proteins in sodium dodecyl sulfate polyacrylamide gels Biochemical medicine 1985;33 (3):327-333 [PubMed]
  • Separation of enzymically active bovine cytochrome c oxidase monomers and dimers by high performance liquid chromatography Journal of inorganic biochemistry 1985;23 (3-4):381-388 [PubMed]

1982

  • The effect of storage on platelet morphology Transfusion 1982;22 (2):115-120 [PubMed]