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Dr. T.B.M. Hakvoort

Position
Scientific staff member (UD)
Main activities
Research, Teaching
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).

Key publications
  • He Y, Hakvoort TBM, Vermeulen JLM, Labruyère WT, de Waart DR, van der Hel WS, Ruijter JM, Uylings HBM, Lamers WH, Glutamine Synthetase Deficiency in Murine Astrocytes Results in Neonatal Death. GLIA 2010;58 (6):741-754 [PubMed]
  • He Y, Hakvoort TBM, Köhler SE, Vermeulen JLM, de Waart DR, de Theije C, ten Have GAM, van Eijk HMH, Kunne C, Labruyere WT, Houten SM, Sokolovic M, Ruijter JM, Deutz NEP, Lamers WH, Glutamine Synthetase in Muscle Is Required for Glutamine Production during Fasting and Extrahepatic Ammonia Detoxification. J BIOL CHEM 2010;285 (13):9516-9524 [PubMed]
  • Sokolović M, Sokolović A, van Roomen CPAA, Gruber A, Ottenhoff R, Scheij S, Hakvoort TBM, Lamers WH, Groen AK, Unexpected effects of fasting on murine lipid homeostasis - Transcriptomic and lipid profiling. J HEPATOL 2010;52 (5):737-744 [PubMed]
  • Sokolović M, Sokolović A, Wehkamp D, Ver Loren van Themaat E, de Waart DR, Gilhuijs-Pederson LA, Nikolsky Y, van Kampen AHC, Hakvoort TBM, Lamers WH, The transcriptomic signature of fasting murine liver. BMC GENOMICS 2008;9 (1):528 [PubMed]
  • Stanulović VS, Kyrmizi I, Kruithof-de Julio M, Hoogenkamp M, Vermeulen JLM, Ruijter JM, Talianidis I, Hakvoort TBM, Lamers WH, Hepatic HNF4alpha deficiency induces periportal expression of glutamine synthetase and other pericentral enzymes. HEPATOLOGY 2007;45 (2):433-444 [PubMed]
All Publications
Research programmes

Prof. dr. G.R. van den Brink MD PhD (Intestinal mucosal homeostasis and it's deregulation in inflammatory bowel disease and during oncogenesis)

Prof. dr. W.J. de Jonge (Gastro-Intestinal diseases)