Mulder, Jaap

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Towards treatment of cholestatic liver disease in children via interference with transcriptional regulation of hepatic transport systems

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   University of GroningenTowards treatment of cholestatic liver disease in children via interference with transcriptionalregulation of hepatic transport systemsMulder, JaapIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2009Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Mulder, J. (2009). Towards treatment of cholestatic liver disease in children via interference withtranscriptional regulation of hepatic transport systems. Groningen: s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 12-11-20198183curriculum viTaeJaap Mulder werd op 30 maart 1978 geboren in Leeuwarden. Na het behalen van het Gymnasiumdiploma aan de CSG Liudger in Drachten in 1995 studeerde hij twee jaar op Kenyon College (Gambier, Ohio, VS). In 1997 begon hij met de studie Ge-neeskunde aan de Rijksuniversiteit Groningen. Als student deed hij onderzoek bij de afdelingen Klinische Farmacologie en Nefrologie (begeleiders: prof.dr. D. de Zeeuw, dr. H.L. Hillege en prof. dr. P.E. de Jong), en later bij de afdeling Kindergeneeskunde (begeleider: prof.dr. F. Kuipers). In de zomer van 2000 nam hij deel aan de Junior Scientific Masterclass (begeleiding prof.dr. T.H. The). Van december 2000 tot augus-tus 2001 was hij in het kader van de Wetenschappelijk Keuzestage werkzaam bij de afdeling Pediatric Nephrology aan The University of Texas Southwestern Medical Center (Dallas, Texas, VS; begeleiders M. Baum, M.D. en R. Quigley, M.D.). Het propaedeutisch (1998) en doctoraal examen (2002) werden cum laude behaald. Van 2001 tot 2003 doorliep hij zijn co-schappen in het Scheper Ziekenhuis in Emmen en het Medisch Spectrum Twente in Enschede, waarna het artsexamen in augustus 2003 werd behaald. Hierna werkte hij een jaar als Postdoctoral Fellow – M.D. bij de afdeling Pediatric Gastroenterology van Baylor College of Medicine (Houston, Texas, VS; begeleider S.J. Karpen, M.D., Ph.D.), deels gefinancierd door het Ter Meu-len Fonds en de European Society for Paediatric Research. In september 2004 begon hij als Agiko bij het researchlaboratorium Kindergeneeskunde van het Universitair Medisch Centrum Groningen (promotores prof.dr. F. Kuipers en prof.dr. P.J.J. Sauer) gefinancierd door ZonMW (Agiko stipendium NR-920-03-287). Van april 2006 tot april 2007 doorliep hij het eerste jaar van de opleiding tot kinderarts in de Beatrix Kinderkliniek van het UMCG (opleider prof.dr. P.J.J. Sauer) en in april 2008 hervatte hij de opleiding in het Martini Ziekenhuis in Groningen (opleider dr. W.B. Geven).8184BiBliographyPinto-Sietsma SJ, Mulder J, Janssen WM, Hillege HL, de Zeeuw D, de Jong PE.  Smoking is related to albu-minuria and abnormal renal function in nondiabetic persons. Ann Intern Med 2000 Oct 17;133(8):585-591.Mulder J, Baum M, Quigley R. Diffusional water permeability (PDW) of adult and neonatal rabbit renal brush border membrane vesicles. J Membr Biol 2002;187(3):167-174.Mulder J, Haddad MN, Vernon K, Baum M, Quigley R. Hypothyroidism increases osmotic water perme-ability (Pf) in the developing renal brush border membrane. Pediatr Res 2003;53(6):1001-1007.Quigley R, Mulder J, Baum M. Ontogeny of water transport in the rabbit proximal tubule. Pediatr Nephrol 2003;18(11):1089-1094.Mulder J, Chakravarty S, Haddad MN, Baum M, Quigley R. Glucocorticoids increase osmotic water perme-ability (Pf) of neonatal rabbit renal brush border membrane vesicles. Am J Physiol Regul Integr Comp Physiol 2005;288(5):R1417-R1421.Ghose R, Mulder J, von Furstenberg RJ, Thevananther S, Kuipers F, Karpen SJ. Rosiglitazone attenuates suppression of RXRα-dependent gene expression in inflamed liver. J Hepatol 2007;46(1):115-123.Mulder J, Karpen SJ, Tietge UJF, Kuipers F. Nuclear Receptors: mediators and modifiers of inflammation-induced cholestasis. Front Biosc 2009;14:2599-2630.Mulder J, Ghose R, Von Furstenberg R, Thevananther S, Kuipers F, Karpen SJ. The LXR-agonist T0901317 attenuates endotoxin-induced changes in hepatobiliary transporter gene expression in mice. Under revision 2009.Mulder J, De Vries J, Kamps JA, Karpen SJ, Sturm E, Kuipers F. Liver X receptor agonist T0901317 attenuates the inflammatory response in primary rat Kupffer cells. In preparation 2009.Mulder J, Wolters H, Huijkman NCA, Bloks VW, Hageman J, Havinga R, Tietge UJF, Karpen SJ, Sturm E, Kuipers F. Dysregulation of biliary cholesterol secretion during inflammation in mice. In preparation 2009.

University of Groningen Research Database

  
 University of Groningen
Towards treatment of cholestatic liver disease in children via interference with transcriptional
regulation of hepatic transport systems
Mulder, Jaap
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from
it. Please check the document version below.
Document Version
Publisher's PDF, also known as Version of record
Publication date:
2009
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Mulder, J. (2009). Towards treatment of cholestatic liver disease in children via interference with
transcriptional regulation of hepatic transport systems Groningen: s.n.
Copyright
Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the
author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).
Take-down policy
If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately
and investigate your claim.
Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the
number of authors shown on this cover page is limited to 10 maximum.
Download date: 11-02-2018
Towards TreaTmenT of cholesTaTic liver disease in
children via inTerference wiTh TranscripTional
regulaTion of hepaTic TransporT sysTems
Jaap mulder
Publication of this thesis is financially supported by:
ZonMW
Rijksuniversiteit Groningen
Faculteit der Medische Wetenschappen
Groningen University Institute for Drug Exploration
Nederlandse Vereniging voor Hepatologie
Unilever
Nestlé Nutrition
The studies described in this thesis were financially supported by:
ZonMW
KNAW Ter Meulen Fonds
European Society for Paediatric Research
Top Institute Pharma 
National Institutes of Health
The Texas Children’s Hospital Foundation
Public Health Service 
Colofon
Layout and Cover Johan Gibcus
ISBN   978-90-367-3776-0
Printer   JAKS, Wroclaw, Poland
Jaap Mulder © 2009
proefschrifT
ter verkrijging van het doctoraat in de
Medische Wetenschappen
aan de Rijksuniversiteit Groningen
op gezag van de
Rector Magnificus, dr. F. Zwarts,
in het openbaar te verdedigen op
woensdag 29 april 2009
om 16.15 uur
door
Jaap mulder
geboren op 30 maart 1978
te Leeuwarden
Towards TreaTmenT of cholesTaTic liver disease in
children via inTerference wiTh TranscripTional
regulaTion of hepaTic TransporT sysTems
Promotores:   Prof. dr. F. Kuipers
    Prof. dr. P.J.J. Sauer
Beoordelingscommissie: Prof. dr. H.J. Verkade
    Prof. dr. A.K. Groen 
    Prof. dr. B. Staels
Voor Mirjam
Voor mijn ouders
Paranimfen:   Mark Mulder
    Rik Hennekam
conTenTs
chapTer 1
Introduction 9
Scope of this thesis 26
chapTer 2
Nuclear receptors: mediators and modifiers of inflammation induced cholestasis 
Adapted from Frontiers in Bioscience, 2009; 14: 2599-2630 33
chapTer 3
Rosiglitazone attenuates suppression of RXRα-dependent gene expression in inflamed liver 
Journal of Hepatology, 2007; 46(1):115-23 81
chapTer 4
The LXR-agonist T0901317 attenuates endotoxin-induced changes in hepatobiliary 
transporter gene expression in mice 
Under revision 97
chapTer 5
Liver X receptor agonist T0901317 attenuates the inflammatory response in primary rat 
Kupffer cells 
In preparation 119
chapTer 6
Dysregulation of biliary cholesterol secretion during inflammation in mice 
In preparation 133
chapTer 7
General discussion 155
Future perspectives 162
appendices
English summary 169
Nederlandse samenvatting 172
List of abbreviations 177
Dankwoord 179
Curriculum vitae 183
Bibliography 184



Towards treatment of cholestatic liver disease in children via interference with transcriptional regulation of hepatic transport systems

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