Citation
Castro Perez, J. M. (2011, October 18). Dynamic system-wide mass
spectrometry based metabolomics approach for a new Era in drug research.
Retrieved from https://hdl.handle.net/1887/17954
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden
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Dynamic System-Wide Mass Spectrometry based Metabolomics Approach
for a New Era in Drug Research
Dynamic System-Wide Mass Spectrometry based Metabolomics Approach for a New Era in Drug Research
José M. Castro Pérez
PhD thesis with summary in Dutch October 2011
ISBN: 978-90-74538-76-3
©2011 José M. Castro Pérez. All rights reserved. No part of this thesis may be reproduced or transmitted in any forms or by any means without written permission from the author.
Cover: Leonardo Da Vinci Vitruvian man drawing (circa 1487) Printed by: Wöhrmann printing service, Zutphen, the Netherlands
Dynamic System-Wide Mass Spectrometry based Metabolomics Approach for a New Era in Drug Research
Proefschrift
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof.mr.P.F. van der Heijden,
volgens besluit van het College voor Promoties te verdedigen op dinsdag 18 oktober 2011
klokke 16:15 uur
door
José M. Castro Pérez
Promotiecommisie
Promotor : Prof. Dr. T. Hankemeier Co-promotores: Dr. R.J. Vreeken Dr. T.P. Roddy Overige leden: Prof. Dr. M. Danhof
Prof. Dr. J. van der Greef Prof. Dr. B. van der Water
Dr. A. Millar
Prof. Dr. C. Fernandez-Hernandez
Dr. D.G. Johns
Chapter 1. General introduction and scope...7 Part I – LC/MS platform development
Chapter 2. Comprehensive shotgun LC-MSE lipidomic analysis in osteoarthritis patients ...26 Chapter 3. Ion mobility mass spectrometry with dual stage CID fragmentation enables localization of
fatty acyl and double bond positions in phosphatidylcholines...70 Part II- Lipid modulating therapies; evaluation of animal models and siRNA mediated KD
Chapter 4. Anacetrapib a novel cholesteryl ester transfer protein inhibitor
and its evaluation on the dyslipidemic Syrian golden hamster animal model ...103 Chapter 5. Liver steatosis induced by siRNA ApoB KD followed by combination siRNA therapy
with loss of function for fatty acid transport protein 5 (Fatp5) KD...127 Chapter 6. Non-HDL cholesterol and ApoB was lowered following in-vivo silencing of Slc27a5 gene
expression in C57Bl/6 mice ...156 Part III- Stable isotope tracers and metabolic flux analysis by LC/MS
Chapter 7. Stable isotope metabolic tracer to measure bile acid reconjugation in-vitro
and in-vivo by UPLC/TOF-MS...191 Chapter 8. In-vivo 'heavy water' labeling in C57Bl/6 mice to quantify static and kinetic changes
Publication List ...273 Curriculum Vitae ...277 Acknowledgements...278
