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Cover Page The handle http://hdl.handle.net/1887/38868 holds various files of this Leiden University dissertation

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The handle http://hdl.handle.net/1887/38868 holds various files of this Leiden University dissertation

Author: Heemskerk, A.A.M.

Title: Exploring the proteome by CE-ESI-MS Issue Date: 2016-04-28

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175

Dankwoord / Acknowledgments

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First and foremost I would like to thank my parents for teaching me to always think before asking a question. They constantly encouraged me to keep thinking and be curious which helped me become a scientist. Besides my parents I of course have to thank my brother who has been there my whole life and in more recent years has become a sparring partner in discussions about varying subjects.

Next up to thank are my three best friends Jasper, Jaap and Rutger. I’ve known these guys for varying lengths of time but all no shorter than about 14 years now. Long term friendships like that are very valuable and they have always provided me with a great escape with social gatherings if the stress/irritation of the research was getting to me.

During my 4 years at the LUMC I only had the privilege to supervise one intern.

Guinevere, thank you for your hard work and help during your period as a student and I’m very happy you found a spot as a PhD student in our group. Next up are naturally my two Para nymphs Frank and Hulda. I met Frank during my studies at the VU and though we did not interact to much then I was happy to hear he secured himself a position at the LUMC and has been a great friend and colleague ever since. Hulda, I met as part of ‘team Iceland’ during the ‘fundamentals of analytical chemistry’ course at the VU university. Shortly after she also started her masters internship at the LUMC and continued as a PhD student. You both have been a large part of making going to work fun as even when the science wasn’t going so well the going to work was never dull.

Next up are my office mates over the years. I started sharing an office with Judith, Tiziana, Irina, Paul, Katja and Oleg. This was a fun year and on average probably the most productive year of my four years. The vibe in the office was always very good and very conducive for loads of work to be done. After a year I had to move to a new office.

Thank you, Simone, Kate, Suzanne, Dana, Tugce, Hans, Irene and Linda for sparing, discussing and support. Naturally there are some colleagues I worked with very well but did not share an office with. Bart, Rico, Rob and Alex, thank you for all the help you provided with experiments equipment software, everything that was needed. Thank you to all the people that helped me with experiments, and through collaborations, discussions. In particular Magnus and Yassene who together with Dana were part of one of the chapters in this thesis.

All the guys from the imaging group, Clara, Bram, Ricardo, Sha and Ruben, though we haven’t collaborated you were valued colleagues and always fun to hang with. The same goes for our NMR warriors, Sarantos, Aswin and Sibel. And I cannot forget Isabel,

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177 Dick Paul and Martin, all three did not fit in any of the above groups but were awesome.

I’m sure I’m forgetting a number of people that were at the LUMC for shorter or longer periods during my four years. All of you made my time what it is and I want to thank you for that.

Last but not least I need to thank the 3 men that most of all made this thesis possible.

Jean-Marc is the person that trained me on the CE system and helped me give my research a running start. Finally, Oleg and André fortunately saw enough in me to hire me for the open position 5 years ago. Thank you for guiding, supervising, and molding me over the last few years. I’ve significantly grown as a person and that is thanks to you and everyone at the LUMC

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179

Curriculum Vitae

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181 Anthonius (Anton) Adrianus Maria Heemskerk was born on October 3rd 1985 in Haarlem, the Netherlands to Johannes Nicolaas Maria Heemskerk and Anja Gijsbertha Maria Heemskerk - van der Aar. He attended the Rozenbeek grade school in Velserbroek, the Netherlands from grades 1 through 8. Subsequently, he attended the Mendel College schooling community and obtained his high school diploma at the Atheneum level in both the Nature & Science and Nature & Health profiles. His high school career was concluded with a year as a foreign exchange student at Cape Central High school in Cape Girardeau, Missouri, USA.

Anton’s education was continued at the VU University in Amsterdam where he obtained a bachelor’s degree in chemistry. During his bachelor’s degree the major research project was performed under the supervision of Dr. Niels Martha in development of on-line reaction monitoring for a catalysed multi-component reaction and using mass spectrometric detection.

The bachelor internship sparked an interest in analytical sciences and resulted in the following of the ‘analytical sciences’ master program at the VU University. During this master program two internships were followed. A 3 month minor internship under the supervision of Dr. Gert van der Zwan and Dr. Michal Heger to research the influence of infra-red light on enzyme kinetics resulted in a publication in Journal Photochemistry and photobiology B. A 7-month master internship was supervised by Dr. John Stobaugh and Dr. Leon van Haandel at the University of Kansas, Lawrence, Kansas, USA. The internship covered the analysis of drug metabolites in human blood by HPLC-LIF and HPLC-MS and resulted in several publications.

Following the master’s degree a PhD position in the development of CE-MS strategies for proteomics analysis became available at the LUMC. The results of research project can be found in this thesis. After the 4 year PhD period Anton continued his career as a CE application specialist with Sciex separations for which he moved to Germany in April 2015.

As of December 2015 he is back in the Netherlands in his current position as a lecturer/

Teacher in the field of (analytical) chemistry at the Hogeschool in Leiden.

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183

List of Publications

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In this thesis

Heemskerk AAM, Busnel J-M, Schoenmaker B, Derks RJE, Klychnikov O, Hensbergen PJ, Deelder AM, Mayboroda OA. Ultra-Low Flow Electrospray Ionization-Mass Spectrometry for Improved Ionization Efficiency in Phosphoproteomics. Analytical chemistry. 2012;84:4552-9.

Ramautar R, Heemskerk AAM, Hensbergen PJ, Deelder AM, Busnel J-M, Mayboroda OA. CE–MS for proteomics: Advances in interface development and application. Journal of proteomics. 2012;75:3814-28.

Heemskerk AAM, Wuhrer M, Busnel J-M, Koeleman CAM, Selman MHJ, Vidarsson G, Kapur R, Schoenmaker B, Derks RJE, Deelder AM, Mayboroda OA. Coupling porous sheathless interface MS with transient-ITP in neutral capillaries for improved sensitivity in glycopeptide analysis. Electrophoresis. 2013;34:383-7.

Heemskerk AAM, Deelder AM, Mayboroda OA. CE–ESI-MS for bottom-up proteomics:

Advances in separation, interfacing and applications. Mass spectrometry reviews. 2014.

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185

Not in this thesis

Martha CT, Heemskerk A, Hoogendoorn J-C, Elders N, Niessen WMA, Orru RVA, Irth H. High-Throughput Reaction Optimisation and Activity Screening of Ferrocene-Based Lewis Acid–Catalyst Complexes by Using Continuous-Flow Reaction Detection Mass Spectrometry. Chemistry – A European Journal. 2009;15:7368-75.

Heger M, Heemskerk AAM, van der Zwan G. Absence of 633-nm laser irradiation- induced effects on glucose phosphorylation by hexokinase. Journal of Photochemistry and Photobiology B: Biology. 2010;98:216-22.

van Haandel L, Heemskerk AAM, Becker ML, Leeder JS, Stobaugh JF. Expedient methodology for total methotrexate polyglutamation pool determination in human erythrocytes. Analytical Methods. 2010;2:831-6.

Heemskerk AAM, van Haandel L, Woods JM, McCance-Katz EF, Williams TD, Stobaugh JF, Faiman MD. LC-MS/MS method for the determination of carbamathione in human plasma. Journal of pharmaceutical and biomedical analysis. 2011;54:799-806.

Viner R, Heemskerk AAM, Horn DM, Saba J, Bern M, Bush D, Santos M, Dewald H, Ivanov AR, Karger BL. Comprehensive Analysis of Recombinant Human Erythropoietin Glycoforms by Capillary Electrophoresis and Nanoflow Liquid Chromatography Coupled with Middle-down Mass Spectrometry.2014.

Fleurbaaij F, Heemskerk AAM, Russcher A, Klychnikov OI, Deelder AM, Mayboroda OA, Kuijper EJ, van Leeuwen HC, Hensbergen PJ. Capillary-Electrophoresis Mass Spectrometry for the Detection of Carbapenemases in (Multi-)Drug-Resistant Gram- Negative Bacteria. Analytical chemistry. 2014;86:9154-61.

Winefield RD, Heemskerk AAM, Kaul S, Williams TD, Caspers MJ, Prisinzano TE, McCance-Katz EF, Lunte CE, Faiman MD. N-Acetyl-S-(N,N-diethylcarbamoyl) cysteine in rat nucleus accumbens, medial prefrontal cortex, and in rat and human plasma after disulfiram administration. Journal of pharmaceutical and biomedical analysis.

2015;107:518-25.

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