Research Topics
Genomes and Genes
| Leo W J KlompSummaryAffiliation: University Medical Center Country: The Netherlands Publications
| Collaborators
|
Detail Information
Publications
Molecular characterization of 3-phosphoglycerate dehydrogenase deficiency--a neurometabolic disorder associated with reduced L-serine biosynthesisL W Klomp
Department of Metabolic Diseases, University Medical Center Utrecht, 3584 AE Utrecht, The Netherlands
Am J Hum Genet 67:1389-99. 2000....
Control by signaling modulators of the sorting of canalicular transporters in rat hepatocyte couplets: role of the cytoskeletonM G Roma
Institute of Experimental Physiology, CONICET University of Rosario, Argentina
Hepatology 32:1342-56. 2000..A second pathway is activated by DBcAMP activation via Ca(2+)-calmodulin formation, whose requirements with respect to cytoskeletal components are opposite. PKC has a negative regulatory role in both pathways...- Characterization of mutations in ATP8B1 associated with hereditary cholestasisLeo W J Klomp
Department of Metabolic and Endocrine Diseases, University Medical Center, Utrecht, The Netherlands
Hepatology 40:27-38. 2004..16% in BRIC). Some mutations, however, lead to a wide range of phenotypes, from PFIC to BRIC or even no clinical disease. ATP8B1 mutations were detected in 30% and 41%, respectively, of the PFIC and BRIC patients screened... - Distinct Wilson's disease mutations in ATP7B are associated with enhanced binding to COMMD1 and reduced stability of ATP7BPrim de Bie
Laboratory of Metabolic and Endocrine Diseases, Division of Biomedical Genetics, Department of Medical Genetics, University Medical Center, Utrecht, The Netherlands
Gastroenterology 133:1316-26. 2007..ATP7B interacts with COMMD1, a protein that is deleted in Bedlington terriers with hereditary copper toxicosis. Here we characterized the implications of the interaction between COMMD1 and ATP7B in relation to the pathogenesis of WD... 
Reduced expression of ATP7B affected by Wilson disease-causing mutations is rescued by pharmacological folding chaperones 4-phenylbutyrate and curcuminPeter V E van den Berghe
Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, and the Netherlands Metabolomics Center, Utrecht, The Netherlands
Hepatology 50:1783-95. 2009..CONCLUSION: These findings might enable novel treatment strategies in WD by directly enhancing the protein expression of mutant ATP7B with residual copper export activity. 1795.)...- The copper-transporting capacity of ATP7A mutants associated with Menkes disease is ameliorated by COMMD1 as a result of improved protein expressionWillianne I M Vonk
Department of Metabolic and Endocrine Diseases, Netherlands Metabolomics Center, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands
Cell Mol Life Sci 69:149-63. 2012..Together, the presented data might provide a new direction for developing therapies to improve the residual exporting activity of unstable ATP7A mutant proteins, and suggests a potential role for COMMD1 in this process... - Kidneys of mice with hereditary tyrosinemia type I are extremely sensitive to cytotoxicitySaskia M M Jacobs
Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, Utrecht, The Netherlands
Pediatr Res 59:365-70. 2006.... - Liver-specific Commd1 knockout mice are susceptible to hepatic copper accumulationWillianne I M Vonk
Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, and Netherlands Metabolomics Center, Utrecht, The Netherlands
PLoS ONE 6:e29183. 2011.... - Monitoring bile acid transport in single living cells using a genetically encoded Förster resonance energy transfer sensorLieke M van der Velden
Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands
Hepatology 57:740-52. 2013..CONCLUSION: A genetically encoded fluorescent BAS was developed that allows intracellular imaging of bile acid homeostasis in single living cells in real time... - Cu,Zn superoxide dismutase maturation and activity are regulated by COMMD1Willianne I M Vonk
Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, The Netherlands
J Biol Chem 285:28991-9000. 2010..Here, we identify COMMD1 as a novel protein regulating SOD1 activation and associate COMMD1 function with the production of free radicals... - Two mass-spectrometric techniques for quantifying serine enantiomers and glycine in cerebrospinal fluid: potential confounders and age-dependent rangesSabine A Fuchs
Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, Utrecht, The Netherlands
Clin Chem 54:1443-50. 2008..Therefore, high-throughput analysis techniques are warranted to determine D-amino acids in biological fluids in a routine laboratory setting... - Gene expression profiling of liver cells after copper overload in vivo and in vitro reveals new copper-regulated genesPatricia Muller
Laboratory for Metabolic and Endocrine Diseases, University Medical Centre, Utrecht, The Netherlands
J Biol Inorg Chem 12:495-507. 2007..In conclusion, we identified a novel set of genes that represent a delayed response to copper overload, thus providing insight into the adaptive transcriptional response to copper-induced oxidative stress... - Folding defects in P-type ATP 8B1 associated with hereditary cholestasis are ameliorated by 4-phenylbutyrateLieke M van der Velden
Department of Metabolic and Endocrine Diseases, University Medical Center UMC Utrecht, The Netherlands
Hepatology 51:286-96. 2010..We propose that treatment with pharmacological chaperones may represent an effective therapeutic strategy to ameliorate the recurrent attacks of cholestasis in patients with intermittent (BRIC1) disease... - Characterization of COMMD protein-protein interactions in NF-kappaB signallingPrim de Bie
Laboratory of Metabolic and Endocrine Diseases, University Medical Center, Utrecht, 3584 EA, The Netherlands
Biochem J 398:63-71. 2006..Taken together, these data support the significance of COMMD protein-protein interactions and provide new mechanistic insight into the function of this protein family in NF-kappaB signalling... - Increased concentrations of both NMDA receptor co-agonists D-serine and glycine in global ischemia: a potential novel treatment target for perinatal asphyxiaSabine A Fuchs
Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, Postbox 85090, 3508 AB, Utrecht, The Netherlands
Amino Acids 43:355-63. 2012..Influencing these NMDAr co-agonist concentrations provides an interesting treatment target for this common, devastating and currently poorly treatable condition... - New developments in the regulation of intestinal copper absorptionPeter V E van den Berghe
Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands
Nutr Rev 67:658-72. 2009.... - Cerebrospinal fluid D-serine and glycine concentrations are unaltered and unaffected by olanzapine therapy in male schizophrenic patientsSabine A Fuchs
Department of Metabolic and Endocrine Diseases and Department of Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
Eur Neuropsychopharmacol 18:333-8. 2008.... - Bile acids and their nuclear receptor FXR: Relevance for hepatobiliary and gastrointestinal diseaseRaffaella M Gadaleta
Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
Biochim Biophys Acta 1801:683-92. 2010..Given the availability of highly potent synthetic FXR agonists, we focus particularly on potential relevance for human disease... - Human copper transporter 2 is localized in late endosomes and lysosomes and facilitates cellular copper uptakePeter V E van den Berghe
Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands
Biochem J 407:49-59. 2007..This work suggests a role for endosomal and lysosomal copper pools in the maintenance of cellular copper homoeostasis... - Heteromeric interactions required for abundance and subcellular localization of human CDC50 proteins and class 1 P4-ATPasesLieke M van der Velden
Department of Metabolic and Endocrine Diseases, Universitair Medisch Centrum Utrecht, AB Utrecht, The Netherlands
J Biol Chem 285:40088-96. 2010..The interactions of CDC50A and CDC50B with multiple members of the human P(4)-ATPase family suggest that these proteins perform broader functions in human physiology than thus far assumed... - D-serine in the developing human central nervous systemSabine A Fuchs
Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, Utrecht, The Netherlands
Ann Neurol 60:476-80. 2006..In one patient treated prenatally, D-serine concentration was nearly normal at birth and the clinical phenotype was normal. These observations suggest a pivotal role for D-serine in normal and aberrant human brain development... - Liver disease associated with canalicular transport defects: current and future therapiesJanneke M Stapelbroek
Department of Paediatric Gastroenterology, Wilhelmina Children s Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands
J Hepatol 52:258-71. 2010..This review will focus on the therapy that is currently available as well as on those developments that are likely to influence clinical practice in the near future... - Nasobiliary drainage induces long-lasting remission in benign recurrent intrahepatic cholestasisJanneke M Stapelbroek
Department of Pediatric Gastroenterology, University Medical Center Utrecht, The Netherlands
Hepatology 43:51-3. 2006..In conclusion, we propose that temporary endoscopic nasobiliary drainage should be considered in cholestatic BRIC patients... - Nuclear-cytosolic transport of COMMD1 regulates NF-kappaB and HIF-1 activityPatricia A J Muller
Department of Metabolic and Endocrine Diseases, UMC Utrecht, Utrecht, The Netherlands
Traffic 10:514-27. 2009..In conclusion, these data indicate that COMMD1 undergoes constitutive nucleocytoplasmic transport as a novel mechanism to regulate NF-kappaB and HIF-1 signaling... - Fic1 is expressed at apical membranes of different epithelial cells in the digestive tract and is induced in the small intestine during postnatal development of miceSaskia W C van Mil
Department of Pediatric Gastroenterology, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands
Pediatr Res 56:981-7. 2004..We speculate that the developing bile salt pool in the maturing intestine accounts for the increase in Fic1 protein expression in this tissue... - Posttranslational regulation of copper transportersPeter V E van den Berghe
Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, The Netherlands
J Biol Inorg Chem 15:37-46. 2010..In this review we systematically discuss the contribution of these different mechanisms to the regulation of copper transport... - The H1069Q mutation in ATP7B is associated with late and neurologic presentation in Wilson disease: results of a meta-analysisJanneke M Stapelbroek
Department of Pediatric Gastroenterology, Wilhelmina Children s Hospital, University Medical Center, P O Box 85090, 3508 AB Utrecht, The Netherlands
J Hepatol 41:758-63. 2004..We examined whether H1069Q, the most common ATP7B mutation, is associated with a specific phenotype... - D-serine influences synaptogenesis in a p19 cell modelSabine A Fuchs
Department of Metabolic and Endocrine Diseases Department of Biomedical Genetics, University Medical Center Utrecht, 85090, 3508 AB, Utrecht, The Netherlands
JIMD Rep 6:47-53. 2012..In addition, this may provide a pathophysiological mechanism for a role of D-serine deficiency in psychiatric disorders... - Biochemical and cellular functions of P4 ATPasesLieke M van der Velden
Department of Metabolic and Endocrine Diseases, UMC Utrecht, and Netherlands Metabolomics Centre, Utrecht, 3508 AB, The Netherlands
Biochem J 431:1-11. 2010..In the present review, we outline the current knowledge of the biochemical and cellular functions of P4 ATPases in the eukaryotic membrane... - ATP8B1 is essential for maintaining normal hearingJanneke M Stapelbroek
Department of Pediatric Gastroenterology, University Medical Center Utrecht, Utrecht, The Netherlands
Proc Natl Acad Sci U S A 106:9709-14. 2009..This indicates that the mechanosensory function and integrity of the cochlear hair cells is critically dependent on ATP8B1 activity, possibly through maintaining lipid asymmetry in the cellular membranes of stereocilia... - Renal proximal tubular cells acquire resistance to cell death stimuli in mice with hereditary tyrosinemia type 1Marjanka C Luijerink
Department of Metabolic Diseases, University Medical Center, Utrecht, The Netherlands
Kidney Int 66:990-1000. 2004..FAH knockout mice develop the HT1 phenotype when NTBC treatment is discontinued... - D-amino acids in the central nervous system in health and diseaseSabine A Fuchs
Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, Utrecht, The Netherlands
Mol Genet Metab 85:168-80. 2005..Consequently, the presence and important roles of d-amino acids in higher organisms do not only challenge former theories on mammalian physiology, but also contribute to exciting new insights in human disease... - Benign recurrent intrahepatic cholestasis type 2 is caused by mutations in ABCB11Saskia W C van Mil
Department of Metabolic and Endocrine Diseases, University Medical Center, Utrecht, The Netherlands
Gastroenterology 127:379-84. 2004..We hypothesized that a genetically distinct form of BRIC is associated with mutations in ABCB11. This gene encodes the bile salt export pump (BSEP) and is mutated in PFIC type 2... - Serine-deficiency syndromesTom J de Koning
Department of Metabolic Diseases, University Medical Centre Utrecht, Utrecht, The Netherlands
Curr Opin Neurol 17:197-204. 2004..An overview of the patients with serine-deficiency disorders reported to date, the biochemical findings and the results of treatment with amino acids is presented... - Molecular regulation of copper excretion in the liverCisca Wijmenga
Department of Biomedical Genetics, University Medical Center, Stratenum 2 117, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
Proc Nutr Soc 63:31-9. 2004.... - Benign recurrent intrahepatic cholestasis progressing to progressive familial intrahepatic cholestasis: low GGT cholestasis is a clinical continuumNancy A M van Ooteghem
Department of Gastroenterology, Gastrointestinal Research Unit, University Medical Center, PO Box 85500, 3508, Utrecht GA, The Netherlands
J Hepatol 36:439-43. 2002..In conclusion, the disease of these patients started with the clinical and histopathological characteristics of BRIC but progressed to PFIC... - Extensive changes in liver gene expression induced by hereditary tyrosinemia type I are not normalized by treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC)Marjanka C Luijerink
Department of Metabolic Diseases, Laboratory for Metabolic and Endocrine Diseases, Room KC02.069.1, University Medical Center, Lundlaan 6, 3584 EA Utrecht, The Netherlands
J Hepatol 39:901-9. 2003..CONCLUSIONS: The failure of NTBC to normalize liver gene expression of Fah-/- mice may play a role in rendering the tyrosinemia-affected liver susceptible to development of hepatocellular carcinoma under NTBC treatment... - Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndromePaul Gissen
Section of Medical and Molecular Genetics, University of Birmingham, and Liver Unit, Birmingham Children s Hospital, UK
Nat Genet 36:400-4. 2004..VPS33B encodes a homolog of the class C yeast vacuolar protein sorting gene, Vps33, that contains a Sec1-like domain important in the regulation of vesicle-to-target SNARE complex formation and subsequent membrane fusion...