Annual report 2013 140112 FINAL - University of Groningen · 2014-01-20 · Chemistry and...

faculty of mathematics and natural sciences

department of pharmacy

Analytical Biochemistry

Annual Report 2013 Prof.Dr. Rainer Bischoff 15 January 2014

Analytical Biochemistry › 2

Group Photo Analytical Biochemistry & Mass Spectrometry Center Back row: Kees Bronsema, Turan Gül, Daniël Wilffert, Peter Horvatovich, Nico van de Merbel, Alexander Boychenko, Tao (Larry) Zhang, Natalia Govorukhina, Hjalmar Permentier, Sara Ongay Camacho, Marcel de Vries, Amanda Lucas, Mikhael Sowma, Hong Yumiao, Frank Schalk Front Row: Jos Hermans, Jan Willem Meints, Jolanda Meindertsma, Rainer Bischoff, Margot Jeronimus-Stratingh, Karin Wolters, Tao Yuan, Yun Yang Not on photo: David Siegel, Annie van Dam Address: University of Groningen Department of Pharmacy Analytical Biochemistry Antonius Deusinglaan 1 Postbus 196 9700 AD Groningen The Netherlands

Head of the research group: Prof. Dr. Rainer Bischoff Phone: (+31)-50-363-3338 Fax: (+31)-50-363-7582 E-mail: [email protected] Website: www.biomac.nl


Members of the Research Group: Staff Prof. Dr. Rainer Bischoff Prof. Dr. Peter Horvatovich Prof. Dr. Nico van de Merbel (professor through special appointment) Dr. Natalia Govorukhina Jos Hermans Jan Willem Meints Jolanda Meindertsma (secretary; 0.4 fte) Mass Spectrometry Centre Dr. Hjalmar Permentier Annie van Dam (0.5 fte) Margot Jeronimus-Stratingh (0.5 fte) Post-doctoral researchers Dr. Alexander Boychenko Dr. Sara Ongay Camacho Dr. Karin Wolters (until June 30, 2013) Dr. David Siegel Ph.D. students Kees Bronsema Lorenza Franciosi Berend Hoekman (group Horvatovich) Vikram Mitra (group Horvatovich) Daniël Wilffert Yun Yang Turan Gül Tao Yuan Tao (Larry) Zhang Research Students Georgia Koutsoumpli, Topmaster MPDI Niels Alting, Master Medical Pharmaceutical Sciences Jennifer Schlaman, Bachelor Hanzehogeschool Nadjib Bawary, Master Pharmacy Amanda Lucas, Master Pharmacy Frank Schalk, Bachelor Hanzehogeschool Hong Yumiao, Master Medical Pharmaceutical Sciences Visiting scientists and students Miina Ruokolainen, PhD student, University of Helsinki, Finland, May 2013, EC-MS of drug compounds: “Imitation of phase I metabolism reactions by photocatalysis and electrochemical reactions”. Kundai Sachikonye, Jacobs University Bremen, Germany. June 2013, Summer internship student project: Project: “Discovery and validation of protein biomarkers for cervical cancer”.


Overview 2013

A major highlight of the year 2013 was the promotion of Peter Horvatovich to associate professor in Computational Mass Spectrometry with tenure in June. Peter has been with the group since he started his postdoctoral studies in 2005. As postdoctoral researcher and as assistant professor during his tenure-track, Peter contributed significantly to the development of bioinformatics procedures in the group notably the processing of LC-MS/MS data. Peter built an international reputation over the years for himself and the group in this field, which has recently been acknowledged by his nomination to join the editorial advisory board of the Journal of Proteome Research one of the leading proteomics journals published by the American Chemical Society. I wish Peter success in his future career and welcome him as a colleague in the research group.

Another major event in 2013 was moving from our old location in building 3211 to the new European Research Institute for the Biology of Ageing (ERIBA). By moving the Analytical Biochemistry group we also joined hands with the colleagues from the Mass Spectrometry Center. The move went rather smoothly thanks to the diligent and detailed preparations made notably by Hjalmar Permentier (head of the MS Center) and Jos Hermans. Although we had to move 16 LC-MS systems, about everything was up and running again within 1-2 weeks after the move. Despite some initial scepticism, we quickly started to realize how much we have gained by moving both groups together and by the more intense interaction with colleagues from the science and the medical science faculties. Please take a look at the Annual Report of the MS Center @ www.biomac.nl.

During 2013 we also got together with old and new colleagues at the Department of Pharmacy that focus on chemistry in the wider sense of the term to instil new life into this research program of the Groningen University Research Institute of Drug Exploration (GUIDE). Due to its wider scope, we renamed the program Medicinal Chemistry and Bioanalysis (MCB, see the MCB flyer @ www.biomac.nl)). To inaugurate the program as well as the new laboratory @ ERIBA, we will hold a symposium on August 25-26, 2014 in Groningen and start with a regular program of research presentations and discussions. It’s great to be working in such a stimulating atmosphere!

The end of the year 2013 brought 2 successful grant applications, one by Nico van de Merbel in the area of Biopharmaceuticals and one in the area of Biomarkers. Notably the large program grant from the Dutch Technology Foundation to establish a Biomarker Development Center (BDC) in the Netherlands in collaboration with colleagues from the University Medical Centres in Nijmegen and Rotterdam is a big step forward. It will foster national and international collaborations and bring sustainability to this research line. It is not possible to mention everything that has happened in this very busy year but the finalization of the PhD theses of Julien Roeser and Laurette Prély should not go unmentioned. The continued hard work of especially the staff members of the group to educate the next generation of scientists through a range of courses (see page 27 for an overview) was again a major contribution in 2013. My thanks to everyone who made this possible. I wish you interesting reading of this Annual Report and a successful year 2014. In case you see possibilities for future collaborations, I would be happy to discuss them with you.


Research Projects

1. Cervical Cancer Biomarkers The cervical cancer project is run in collaboration with the groups of Ate van der Zee (UMCG) and Theo Luider (Erasmus University Medical Center, Rotterdam). Coworkers that are actively involved in this project are Natalia Govorukhina and Alexander Boychenko in Groningen and Coskun Güzel in Rotterdam. The project is funded by the Dutch Cancer Society (KWF). Project Description Cervical carcinoma is the second most frequent carcinoma in women worldwide, while in the developing countries cervical carcinoma is the most frequent carcinoma in women. In this project, we are developing new approaches based on LC-MS/MS to detect biomarkers for the early diagnosis and prognosis of cervical cancer based on serum and tissue analyses. Current work focuses on validating biomarker candidates that were discovered by targeted tissue analysis after laser-guided microdissection or through serum analysis. To this end colleagues in Rotterdam developed a 2-dimensional nanoLC-MS/MS method to measure HSP-90 in serum at the ng/mL level without the use of antibodies. After confirming the initially discovered serum biomarker candidates, the Groningen team developed a quantitative LC-MS/MS method in the SRM mode and is currently in the middle of a large verification study comparing healthy controls, with patients with precancerous lesions (CIN) and patients with early- and late-stage cervical carcinoma. Notably the differentiation of patients with CIN lesions that may or may not develop into cancer from healthy controls is challenging but initial data are encouraging (see figure below).

ROC curve for discriminating patients with precancerous CIN lesions from healthy subjects based on the measurement of multiple serum proteins by LC-MS/MS (SRM mode) Area under the ROC curve 0.85.

Next to validating biomarker candidates in a larger set of serum samples, we have initiated another round of discovery work based on laser-guided microdissection of tissue from cancer patients and controls as well as on a more in-depth serum analysis by depleting 64 proteins using immunoaffinity chromatography. To enhance proteome coverage we have developed better sample preparation and separation methods at the peptide level using 2- and 3-dimensional LC.


2. Data processing and statistical analysis (group Horvatovich) This research line has been carried out by two PhD students Vikram Mitra and Berend Hoekman under the supervision of Peter Horvatovich. It is expected that Vikram Mitra and Berend Hoekman will defend their theses in 2014. The fruitful collaboration with Frank Suits from IBM and the group of Gyorgy Marko-Varga at Lund University (Sweden) continued and resulted in two publications on a data pre-processing pipeline for MALDI imaging analysis. Collaboration with the Laboratoire de Chimie Analytique et Sciences de l’Aliment (Strasbourg, France) resulted in a publication on the topic of biomarker discovery to identify Lactic bacilli with probiotic properties. Peter Horvatovich was invited to edit a book on “Comprehensive Biomarker Discovery and Validation for Clinical Application” published by the Royal Chemistry Society (UK) with Rainer Bischoff as co-editor. Peter Horvatovich is further actively involved as member of the Chromosome 5 team of the Chromosome Centric Human Proteome Project, an initiative of the Human Proteome Organization (HUPO). Further research lines that are currently pending to receive funding are the development of a bioinformatics platform for the detection of low abundant peptides and proteins and to the development of a novel sensitive targeted Mass Spectrometry Imaging approach using photo-cleavable mass tags (collaboration with Angela Casini). Project Description The analysis of complex mixtures with hyphenated analytical methods like LC-MS/MS generates enormous amounts of data corresponding to several tens of thousands of compounds (variables) per sample. In order to be able to compare a limited number of samples in typical biomarker discovery projects, it is thus vital to reduce the number of variables without losing relevant information. The way from the raw data to the so-called “clean data” is denominated as data pre-processing. Development of efficient and reliable data pre-processing algorithms requires knowledge of both the mathematical background of the data processing steps as well as a good understanding of the structure of the data and the analytical procedures through which artefacts may have been generated. The work of Christin on the comparative evaluation of six different statistical approaches for biomarker discovery (published in Molecular & Cellular Proteomics) was performed in close collaboration with colleagues at the University of Amsterdam (Age Smilde, Huub Hoefsloot). Berend Hoekman finalized the extension of the msCompare framework for quantitative pre-processing of label-free 2-dimensional LC-MS/MS data and finalized the development of a liquid chromatography gradient optimization method to improve the identification efficiency within a given LC-MS/MS analysis of complex proteomics samples.


Overview of the two best performing feature selection statistical methods for two differentially spiked LC-MS data sets (first dataset: 0a, 0b; second dataset: 1a-c, 2a-c) of different sample size and extent of between- and within-class variability (from Christin et al., Mol. Cell. Prot. 12 (2013) 263-276).

Though Ishtiaq Ahmad is now working at the University of Amsterdam, we are still collaborating on the implementation of a comprehensive complete data (pre)-processing pipeline starting from raw mass spectrometry data all the way to knowledge discovery on the NBIC Galaxy server (http://galaxy.nbic.nl/) in collaboration with several Dutch research groups.

Vikram Mitra finalized his project to develop a quality control method, which assesses whether it is possible to align all peaks in two chromatograms with the same accuracy (paper under review at the J. Proteome Res.). The second manuscript, which describes a statistical approach to analyse data sets obtained in an experimental design study, is at the final stage. This work has the goal to assess the importance of pre-analytical factors affecting the quantitative molecular profile of complex shotgun proteomics samples. The work is performed in close collaboration with our colleagues at the University of Amsterdam (Age Smilde, Gooitzen Zwanenburg). Vikram is also at an advanced stage with his third manuscript on identification transfer between complex LC-MS(/MS) data sets despite the fact that he started his new job at Proteome Sciences plc (London, UK) on April 01, 2013.


3. Electrochemistry The different lines of this project are run in collaboration between the Analytical Biochemistry group & the Mass Spectrometry Center with the Biochemistry/Biotechnology group at the University of Groningen (Marco Fraaije) and the BIOS - lab on a chip group at the University of Twente (Albert van den Berg, Wouter Olthuis and Matthieu Odijk). Work on the electrochemical cleavage of peptides and proteins (Larry Zhang) made progress by performing the subsequent coupling reaction of the spirolactone-containing cleavage product in an organic solvent. The semi-preparative electrochemical synthesis of Phase-I drug metabolites (Turan Gül) has advanced thanks to a systematic optimization using a Design-of-Experiment (DoE) approach and the recent implementation of up-scale equipment. The surface modification of electrodes (Tao Yuan) is currently being studied in detail using surface-enhanced Raman spectroscopy (SERS) in close collaboration with colleagues from the University of Twente. The immobilization of FAD-dependent monooxygenases (Marzena Krzek, group Fraaije) was successful using agarose beads and we are eagerly awaiting results whether this enzyme can be functionally coupled to a surface-modified electrode. The project lines are funded by the Dutch Technology Foundation (STW), the Dutch Research Organization (NWO, ECHO grant, collaboration Fraaije) and the Chinese Scholarship Council (CSC, Larry Zhang). Project Description The projects aim at a) the electrochemical cleavage of peptides and proteins, b) the semi-preparative electrochemical synthesis of Phase-I drug metabolites, c) the surface modification of electrodes and d) the immobilization of FAD-dependent monooxygenases. Output from earlier work has resulted in 2 publications in 2013 in the field of peptide cleavage and capture.

Scale-up of the generation of the N-dealkylation product of lidocaine using a preparative electrochemical batch cell (n=2).


4. Electrospray Ionization Response This work is performed by Jos Hermans and Sara Ongay Camacho. In this project we study the effect of different chemical derivatization reagents on the electrospray ionization response of low-molecular weight analytes in relation to their physico-chemical properties. Project Description Many low-molecular weight hydrophilic compounds are not amenable to high-sensitivity LC-MS analysis using electrospray ionization (ESI). Furthermore, these compounds are often not retained on reversed-phase chromatographic stationary phases and thus escape detection altogether. Earlier work showed that the ionization efficiency of amino acids upon ESI can be markedly enhanced by coupling polyethyleneglycol derivatives to these compounds (Abello et al., Anal. Chem., 2008, 80: 9171). In this project we investigate potential mechanisms underlying this enhancement by correlating the ESI signals of various amino acid derivatives with calculated physico-chemical properties. While there is a clear correlation between the molecular volume and the ESI response for amino acids that are derivatized with aliphatic organic acids, this is not the case for PEG-derivatization (see below). This project will be continued by studying other relationships.

Correlation between the calculated molecular volume and the electrospray ionization response of derivatized amino acids using a flow-injection system. PEG (polyethyleneglycol); BU (butyl); PR (propyl); AC (acetyl); AA-FIA (non-derivatized amino acids)


5. Protein analysis for systems biology As part of the Systems Biology Center for Energy Metabolism and Ageing Research (SBC-EMA) Karin Wolters (postdoctoral researcher) established quantitative protein analysis methodology based on protein-specific peptides by LC-MS/MS in the selected reaction monitoring (SRM) mode. We currently apply these methods to ageing yeast cells (coll. Matthias Heinemann) and mouse models (coll. Barbara Bakker) under different conditions of energy usage and physical activity. Data provided to the colleagues focusing on yeast cells are currently being analysed and integrated into systems biology models. Project Description Development of targeted proteomics assays for yeast

For the assay development of yeast target proteins, isotopically labelled cells (metabolic labelling) were grown under various conditions to achieve maximal coverage for all target proteins. With these samples, assays were developed for proteins belonging to energy metabolism pathways, the nuclear pore complex and other targets related to ageing. Quantitative data has been acquired for the ageing related targets using replicatively aged yeast cells (data acquisition finished; data analysis ongoing). In parallel we are setting up assays to study the composition of the nuclear pore complex (coll. Liesbeth Veenhoff) in yeast cells using the QConCat approach (coll. Rob Beynon, University of Liverpool, UK) for absolute quantification. Development of targeted proteomics assays for mouse Protein extraction from various mouse tissues and organelles has been optimized and absolute quantifications will be obtained using QConCATs specific for a subset of proteins from the energy metabolic and the fatty acid β-oxidation pathways (in total 57 proteins). Targeted protein analyses from a test set of aged mice are ongoing. Expanding the scope of targeted proteomics Possibilities are currently explored to expand the scope of biological questions that can be addressed using targeted proteomics. In one sub-project we study the phosphorylation state of hexokinase 2 at two sites in relation to various glycolytic fluxes in yeast cells (coll. Matthias Heinemann).

T (min) 0 2 5 10 15 20 30 60 90

1P

0P Phosphorylation state of hexokinase 2 in yeast. Upper part: total phosphorylation state determined with a phostag gel (courtesy Guille Zampar). Lower part: total phosphorylation state quantified from the phostag gel (in red) and through quantification of one phosphorylation site by LC-MS/MS (in black). Note the generally better precision of the MS analysis.


6. Metabolite analysis for systems biology

David Siegel (postdoctoral fellow) developed LC-MS/MS methodology to quantify the main metabolites involved in cellular energy metabolism based on LC-MS/MS in the SRM mode. We are currently able to quantify some 70 metabolites using a 13C-labelled global internal standard obtained from yeast cultures grown on 13C-glucose. A number of issues associated with the quantification of highly polar small molecules were investigated as well. For instance, we studied the effect of metal ions in the LC mobile phase on sensitivity and other analytical figures of merit. Eluent modification with a volatile metal chelator was found to resolve related issues and improved almost all analytical performance parameters in typical targeted analyses.

Representation of the effect of eluent modification with a volatile metal chelator (acetylacetone) on UHPLC-ESI(-)-MS/MS peak properties. The chromatograms shown are technical replicates with increasing concentrations of acetylacetone in the UHPLC eluent (CoA = Coenzyme A) (from Siegel et al., J. Chrom. A., 2013, 1294: 87).

A general review of analytical issues in energy metabolite quantification was furthermore published and forms the basis for a PhD project starting in February 2014. In the frame of this project we will systematically study chemical degradation of different classes of metabolites during the pre-analytical phase and develop approaches to address such issues wherever feasible.


7. LC-MS/MS analysis of protein pharmaceuticals in complex biological matrices This project is part of a collaboration with the Pharmaceutical Biology group at the University of Groningen (Wim Quax), with Utrecht University (Ad de Jong) and the Free University of Amsterdam (Wilfried Niessen, Govert Somsen), the Bioanalytical Laboratory at PRA (Nico van de Merbel), and a number of industrial partners funded by the Dutch Technology Foundation (STW). In 2013 we focused on different aspects of the analysis of protein biopharmaceuticals related to protein and peptide enrichment without antibodies and the systematic evaluation of the effect of internal standards on method performance. Major achievements in 2013 were the high-sensitivity analysis of salmon calcitonine in human plasma at 10 pg/mL and the analysis of TRAIL (wild-type and one site-directed variant) in human and mouse serum at 20 ng/mL. Both methods were fully validated according to international guidelines for the bioanalysis of pharmaceuticals (e.g. as stipulated by the FDA). Project Description Protein pharmaceuticals or “biopharmaceuticals” form a class of innovative therapeutic agents that are rapidly increasing in relevance for health care. In order to develop these macromolecules into effective and safe products it is necessary to dispose of analytical methods that can characterize them at the molecular level and that allow to follow them in vivo during clinical development and in clinical practice. In a consortium between leading academic groups in analytical chemistry in the Netherlands, instrument manufacturers and pharmaceutical companies we develop highly sensitive and selective methods for biopharmaceutical analysis. In Groningen, Daniël Wilffert (PhD student), Carlos Reis and Ingrid van Roosmalen (group of Wim Quax) study variants of TRAIL in body fluids and cell culture by LC-MS/MS. The first method for serum analysis has been validated and successfully applied to an in vivo pharmacokinetic study in mice. This method reaches low ng/mL sensitivity without the use of antibodies and allows the simultaneous quantification of TRAIL wild-type and one variant. The project of PhD student Kees Bronsema focuses on the ultra-sensitive,

quantitative analysis of peptide pharmaceuticals and biomarkers by LC-MS/MS in the SRM mode. Next to the low pg/mL quantification of the peptide salmon calcitonine, the antibody-free analysis of single-chain antibodies (so-called nanobodies) has been successfully completed down to the low ng/mL level. We have recently extended these analyses to enzymes that are used in replacement therapy and to monoclonal antibodies in collaboration with the Hospital Pharmacy Department of the University Medical Center Groningen (Daan Touw).

LC-MS/MS of salmon calcitonine in human plasma at 10 pg/mL (from Bronsema et al., Anal.

Chem., 2013, 85: 9528).


8. Development of reversible crosslinkers for histochemistry and proteomics In this project we develop and evaluate reversible chemical crosslinkers that can be cleaved under specified conditions in collaboration with the Pharmacokinetics, Toxicology and Targeting group at the University of Groningen (Geny Groothuis) and a number of collaborating groups in an NWO-funded project as part of the COAST program. Based on progress with the chemical synthesis (Leiden University, group of Hermen Overkleeft) we hope to extend this principle to crosslinkers with added functionalities, for example for easier protein quantification or enrichment. Our initial results show that a reversible crosslinker which can be cleaved with periodate allows recovering more protein from paraffin-embedded fixated tissue. Further proteomics analyses will show whether this translates into more identified proteins. Project Description

Histochemistry (HC) is widely used in pathology to diagnose disease, to prognosticate disease development and to stratify patients for subsequent therapeutic interventions. Histochemistry combined with immunological detection (immunohistochemistry or IHC) is a very important technique in clinical research. HC is based on fixating tissue by protein crosslinking using paraformaldehyde followed by embedding in paraffin. While this allows the detailed microscopic analysis of tissue sections as well as their conservation over extended periods of time at room temperature, it is currently very difficult to perform comparative quantitative protein analyses on fixated and paraffin embedded tissue due to crosslinks between proteins. In an effort to combine tissue fixation with subsequent proteomic analysis, for example after laser-guided microdissection, we initiated a collaborative project between academic groups and industry on novel chemical crosslinkers with added functionality funded by the NWO-ACTS program (sub-program COAST).

SDS-PAGE analysis of crosslinked lysozyme as

surrogate for fixated tissue. A) prior to cleavage with

periodate and B) after cleavage with periodate.


Ph.D. projects: B. Hoekman Development of a comprehensive data processing and statistical analysis methodology for label-free LC-MS data in biomarker discovery Promotor: Prof. Dr. P.L. Horvatovich Co-promotors: Prof. Dr. R. Bischoff, Prof. Dr. R. Breitling (University of Manchester) Start: September 2007 L. Franciosi Acute and chronic inflammatory responses induced by smoking in individuals being susceptible and non-susceptible for development of COPD: from specific disease phenotyping towards novel tailor-made therapy Promotors: Prof. Dr. R. Bischoff, Prof. Dr. D.S. Postma (UMCG), Dr. N.H.T. ten Hacken (UMCG) Supervisor: Dr. N. Govorukhina Start: February 2008 V. Mitra Quantitation, processing and classification algorithms for mass spectrometry Promotor: Prof. Dr. P.L. Horvatovich Co-promotors: Prof. Dr. R. Bischoff, Prof. Dr. A.K. Smilde (University of Amsterdam) Start: April 2009 K. Bronsema Quantitative determination of biopharmaceuticals in biological fluids using LC-MS based techniques Promotors: Prof. Dr. N.C. van de Merbel, Prof. Dr. R. Bischoff Start: September 2010 D. Wilffert Analysis of Biopharmaceuticals by LC-MS/MS Promotors: Prof. Dr. R. Bischoff, Prof. Dr. W.J. Quax, Prof. Dr. N.C. van de Merbel Supervisors: J. Hermans, Dr. N. Govorukhina Start: August 2011 Y. Yang Mixed mode chromatography in proteomic biomarker discovery: focus on nitrotyrosine-modified proteins Promotors: Prof. Dr. R. Bischoff, Prof. Dr. I. Kema (UMCG) Supervisor: Dr. S. Ongay Camacho Start: November 2011 T. Zhang LC-Electrochemistry - Mass Spectrometry in Protein Chemistry Promotors: Prof. Dr. R. Bischoff, Prof. Dr. I. Kema (UMCG) Supervisor: Dr. H. Permentier Start: September 2012 T. Gül Electrochemistry – Mass Spectrometry (EC-MS) for Drug Metabolism Promotor: Prof. Dr. R. Bischoff Supervisor: Dr. H. Permentier Start: September 2012


T. Yuan Electrochemistry combined with mass spectrometry to study drug metabolism Promotor: Prof. Dr. R. Bischoff Supervisor: Dr. H. Permentier Start: October 2012


Scientific Output 2013 Theses Roeser, J., Electrochemical oxidation and cleavage of peptides in bioanalysis. Mechanistic aspects & method development. Promotor: Prof. Dr. R. Bischoff; co-promotors: Dr. A.P. Bruins, Dr. H.P. Permentier. Dissertation University of Groningen, March 8, 2013, 159 pp. Prely, L.M., Activity-based and targeted analyses of matrix-metalloproteases. Promotors: Prof. Dr. R. Bischoff, Prof. Dr. A.J.M. van Oosterhout. Dissertation University of Groningen, October 28, 2013, 108 pp. Scientific publications Peer-reviewed Avanti, C., Hinrichs, W.L.J., Casini, A., Eissens, A.C., Dam, A. van, Kedrov, A., Driessen, A.J.M., Frijlink, H.W., Permentier, H.P., The formation of oxytocin dimers is suppressed by the zinc-aspartate-oxytocin complex. J. Pharmacol. Sci. 102 (2013) 1734-1741 Bischoff, R., Bronsema, K.J., Merbel, N.C. van de, Analysis of biopharmaceutical proteins in biological matrices by LC-MS/MS. I. Sample preparation. Trends Anal. Chem. 48 (2013) 41-51 Boichenko, A., Govorukhina, N., Zee, A.G.J. van der, Bischoff, R., Simultaneous serum desalting and total protein determination with macroporous reversed-phase chromatography. Anal. Bioanal. Chem. 405 (2013) 3195-3203 Boichenko, A.P., Govorukhina, N., Zee, A.G.J. van der, Bischoff, R., Multidimensional separation of tryptic peptides from human serum proteins using reversed-phase, strong cation exchange, weak anion exchange, and fused-core fluorinated stationary phases. J. Sep. Sci. 36 (2013) 3463-3470 Bouma, H.R., Mandl, J.N., Strijkstra, A.M., Boerema, A.S., Kok, J.W., Dam, A. van, IJzerman, A., Kroese, F.G., Henning, R.H., 5'-AMP impacts lymphocyte recirculation through activation of A2B receptors. J. Leukoc. Biol. 94 (2013) 89-98 Bronsema, K.J., Bischoff, R., Merbel, N.C. van de, High-sensitivity LC-MS/MS quantification of peptides and proteins in complex biological samples: The impact of enzymatic digestion and internal standard selection on method performance. Anal. Chem. 85 (2013) 9528-9535 Budnik, L.T., Preisser, A.M., Permentier, H., Baur, X., Is specific IgE antibody analysis feasible for the diagnosis of methylenediphenyl diisocyanate-induced occupational asthma? Int. Arch. Occup. Environ. Health 86 (2013) 417-430 Christin, C., Hoefsloot, H.C.J., Smilde, A.K., Hoekman, B., Suits, F., Bischoff, R., Horvatovich, P., A critical assessment of feature selection methods for biomarker discovery in clinical proteomics. Mol. & Cell. Proteom. 12 (2013) 263-276 Franciosi, L., Govorukhina, N., Fusetti, F., Poolman, B., Lodewijk, M.E., Timens, W., Postma, D., Hacken, N. ten, Bischoff, R., Proteomic analysis of human epithelial lining


fluid by microfluidics-based nanoLC-MS/MS: a feasibility study. Electrophoresis 34 (2013) 2683-2694 Happyana, N., Agnolet, S., Muntendam, R., Dam, A. van, Schneider, B., Kayser, O., Analysis of cannabinoids in laser-microdissected trichomes of medicinal Cannabis sativa using LC-MS and cryogenic NMR. Phytochemistry 87 (2013) 51–59 Langenkamp, E., Kamps. J.A.A.M., Mrug, M., Verpoorte, E., Niyaz, Y., Horvatovich, P., Bischoff, R., Struijker-Boudier, H., Molema, G., Innovations in studying in vivo cell behavior and pharmacology in complex tissues - microvascular endothelial cells in the spotlight. Cell Tissue Res. 34 (2013) 647-669 Lo Tam Loi, A., Hoonhorst, S.J.M., Franciosi, L., Bischoff, R., Hoffmann, R.F., Heijink, I., Oosterhout, A.J.M. van, Boezen, H.M., Timens, W., Postma, D.S., Lammers, J.W., Koenderman, L., Hacken, N.H.T. ten, Acute and chronic inflammatory responses induced by smoking in individuals susceptible and non-susceptible to development of COPD: from specific disease phenotyping towards novel therapy. Protocol of a cross-sectional study. BMJ Open 3 (2013) e002178 Matusiak, N., Waarde, A.V., Bischoff, R., Oltenfreiter, R., Wiele, C.V., Dierckx, R.A., Elsinga, P.H., Probes for non-invasive matrix metalloproteinase-targeted imaging with PET and SPECT. Curr. Pharm. Des. 19 (2013) 4647-4672 Merbel, N.C. van de, Vries, R. de, Aging of biological matrices and its effect on bioanalytical method performance. Bioanalysis 5 (2013) 2393-2407 Meszaros, P., Klappe, K., Dam, A. van, Ivanovac, P.T., Milnec, S.B., Myers, D.S., Brown, H.A., Permentier, H., Hoekstra, D., Kok, J.W., Long term myriocin treatment increases MRP1 transport activity. Int. J. Biochem. Cell Biol. 45 (2013) 326-334 Ongay, S., Hermans, J., Bruins, A.P., Nieuwendijk, A.M.C.H., Overkleeft, H., Bischoff, R., Electron transfer and collision induced dissociation of non-derivatized and derivatized desmosine and isodesmosine. J. Am. Soc. Mass Spectrom. 24 (2013) 83-91 Roeser, J., Alting, N.F.A., Permentier, H.P., Bruins, A.P., Bischoff, R., Chemical labeling of electrochemically cleaved peptides. Rapid Comm. Mass Spectrom. 27 (2013) 546-552 Roeser, J., Alting, N.F., Permentier, H.P., Bruins, A.P., Bischoff, R., Boron-doped diamond electrodes for the electrochemical oxidation and cleavage of peptides. Anal. Chem. 85 (2013) 6623-6632 Siegel, D., Permentier, H., Bischoff, R., Controlling detrimental effects of metal cations in the quantification of energy metabolites via ultrahigh pressure-liquid chromatography-electrospray-tandem mass spectrometry by employing acetylacetone as a volatile eluent modifier. J. Chromatogr. A 1294 (2013) 87-97 Siissalo, S., Waard, H. de, Jager, M.H. de, Frijlink, H.W., Hinrichs, W., Dinter, H., Dam, A. van, Groothuis, G.M.M., Graaf, I.A.M. de, Nanoparticle formulation of a poorly soluble CB-1 antagonist improves absorption by rat and human intestine. Drug Metab. Dispos. 41 (2013) 1557-1565 Somborac-Bačura, A., Toorn, M. van der, Franciosi, L., Slebos, D.J., Žanić-Grubišić, T., Bischoff, R., Oosterhout, A.M.J. van, Cigarette smoke induces endoplasmic reticulum stress response and proteasomal dysfunction in human alveolar epithelial cells. Exp. Physiol. 98 (2013) 316-325


Suits, F., Fehniger, T.E., Vegvari, A., Marko-Varga, G., Horvatovich, P., Correlation queries for mass spectrometry imaging. Anal. Chem. 85 (2013) 4398-4404 Wilffert, D., Reis, C.R., Hermans, J., Govoruhkina, N., Tomar, T., Jong, S. de, Quax, W.J., Merbel, N.C. van de, Bischoff, R., Antibody-free LC-MS/MS quantification of rhTRAIL in human and mouse serum. Anal. Chem. 85 (2013) 10754-10760 Ye, Y., Liu, H., Horvatovich, P., Chan, W., Liquid chromatography-electrospray ionization tandem mass spectrometric analysis of 2-alkylcyclobutanones in irradiated chicken by precolumn derivatization with hydroxylamine, J. Agricul. Food Chem., 61 (2013) 5758–5763 Recently published or accepted Siegel, D., Permentier, H.P., Reijngoud, D.J., Bischoff, R. Chemical and technical challenges in the analysis of central carbon metabolites by liquid-chromatography mass spectrometry. J. Chrom. B (http://dx.doi.org/10.1016/j.jchromb.2013.11.022) Ongay, S., Hendriks, G., Hermans, J., Berge, M. van den, Hacken, N. ten, Merbel, N. van de, Bischoff, R., Quantification of free and total desmosine and isodesmosine in human urine by LC-MS/MS: a comparison of the surrogate-analyte and the surrogate-matrix approach for quantitation. J. Chrom. A (http://dx.doi.org/10.1016/j.chroma.2013.12.035) Horvatovich, P., Franke, L., Bischoff, R., Proteomic studies related to genetic determinants of variability in protein concentrations. J. Proteome Res., 13 (2014), 5-14 Ourailidou, M.E., Meer, J.Y. van der, Baas, B.J., Jeronimus-Stratingh, M., Gottumukkala, A.L., Poelarends, G.J., Minnaard, A.J., Dekker, F.J., Aqueous oxidative Heck reaction as a protein-labeling strategy. Chem.Bio.Chem. (http://dx.doi.org/10.1002/cbic.201300714) Fehniger, E. T., Suits, F., Végvári, A., Horvatovich, P., Foster, M., Marko-Varga, G., Queries of MALDI-MSI global datasets identifying ion mass signatures associated with tissue compartments, Proteomics (accepted) Hamon, E., Horvatovich, P., Marchioni, E., Aoudé-Werner, D., Ennahar, S., Investigation of potential markers of acid resistance in Lactobacillus plantarum by comparative proteomics, accepted in J. Appl. Microbiol., 116 (2014), 134-144 Book & Special Topic Editors Comprehensive biomarker discovery and validation for clinical application. P.L. Horvatovich, R. Bischoff, Eds., RSC Publishing, Drug Discovery Series No. 33, 2013 Jong, G. de, Bischoff, R., Guest Editors special topic Analysis of Biopharmaceuticals in Trends in Analytical Chemistry, vol. 48, July/August 2013, pp. 40-143


Book chapters Horvatovich, P., Bischoff, R., Introduction to biomarker discovery and validation. Preface In: Comprehensive biomarker discovery and validation for clinical application. P. Horvatovich, R. Bischoff, Eds., RSC Publishing, Drug Discovery Series No. 33, 2013, pp. V-VIII Govorukhina, N., Bischoff, R., Sample preparation and profiling: Biomarker discovery in body fluids by proteomics. In: Comprehensive biomarker discovery and validation for clinical application. P. Horvatovich, R. Bischoff, Eds., RSC Publishing, Drug Discovery Series No. 33, 2013, pp. 113-135 Horvatovich, P., Suits, F., Hoekman, B., Bischoff, R., Bioinformatics and statistics: LC-MS(/MS) data preprocessing for biomarker discovery. In: Comprehensive biomarker discovery and validation for clinical application. P. Horvatovich, R. Bischoff, Eds., RSC Publishing, Drug Discovery Series No. 33, 2013, pp. 199-225 Merbel, N.C. van de, LC-MS bioanalysis of interconvertible compounds. In: Handbook of LC-MS Bioanalysis: Best Practices, Experimental Protocols, and Regulations, First Edition, W. Li, J. Zhang and F.L.S. Tse (Eds), John Wiley and Sons, 2013, pp 505-517 Non-peer reviewed Horvatovich, P., Biomarkers, Independent Validation. In: Encyclopedia of Systems Biology, Editors: Werner Dubitzky, Olaf Wolkenhauer, Kwang-Hyun Cho, Hiroki Yokota, ISBN: 978-1-4419-9862-0 (Print) 978-1-4419-9863-7 (online), 2013, p. 126 Horvatovich, P., Biomarkers, Protein Expression. In: Encyclopedia of Systems Biology, Editors: Werner Dubitzky, Olaf Wolkenhauer, Kwang-Hyun Cho, Hiroki Yokota, ISBN: 978-1-4419-9862-0 (Print) 978-1-4419-9863-7 (online), 2013, p. 127 Horvatovich, P., Biomarkers, Solid Tissue. In: Encyclopedia of Systems Biology, Editors: Werner Dubitzky, Olaf Wolkenhauer, Kwang-Hyun Cho, Hiroki Yokota, ISBN: 978-1-4419-9862-0 (Print) 978-1-4419-9863-7 (online), 2013, p. 130 Jong, G. de , Bischoff, R., Editorial: Analysis of biopharmaceuticals. Trends in Anal. Chem. 48 (2013) 40. Lectures Bischoff, R., Profiling and identification of cerebrospinal fluid proteins in a rat EAE model of Multiple Sclerosis. University of Geneva, Switzerland, Jan. 25, 2013 Bischoff, R., From biomarker discovery to electrochemistry. University of Strasbourg, France, March 11, 2013 Bischoff, R., From eQTLs to protein analyses in asthma and COPD. Proteomics Forum 2013, Berlin, Germany, March 17-21, 2013 Bischoff, R., Studying the MMP-9 – TIMP-1 protease-inhibitor system by activity-based enrichment and selected reaction monitoring (SRM) nano-LC-MS/MS. 39th International Symposium on High Performance Liquid Phase Separations and Related Techniques (HPLC 2013), Amsterdam, The Netherlands, June 16-20, 2013


Bischoff, R., Electrochemistry – mass spectrometry in drug metabolism and protein chemistry. EU-COST action CM1201, Zadar, Croatia, Sept. 10-13, 2013 Bischoff, R., Absolute quantitative LC-MS/MS analysis of rhTRAIL in serum. Advanced Analytics for Therapeutic Proteins - from Research to Manufacturing, Dechema, Irsee, Germany, Sept. 18-20, 2013 Bischoff, R., Wie het meet mag het zeggen!, Symposium on the occasion of the retirement of Prof. Gerhardus (Ad) de Jong, Utrecht University, The Netherlands, Nov. 19, 2013 Boichenko A.P., Nano-chip-LC/MS for serum proteome profiling and cervical cancer biomarker discovery, Dutch Society for Mass Spectrometry spring meeting, Bilthoven, The Netherlands, April 11, 2013 Boichenko, A., Discovery and validation of serum biomarkers for cervical cancer by LC-MS/MS. 39th International Symposium on High Performance Liquid Phase Separations and Related Techniques (HPLC 2013), Amsterdam, The Netherlands, June 16-20, 2013 Boichenko A.P., Protein biomarkers for cervical cancer: from shotgun to targeted MS quantification. 13th Netherlands Proteomics Platform Fall Meeting, Amsterdam, The Netherlands, Nov. 8, 2013 Bronsema, K.J., High-sensitivity LC-MS/MS quantitation of peptides and proteins in complex biological samples. Annual Meeting of the NWO/CW study group Analytical Chemistry and COAST, the public-private partnership on Analytical Science & Technology, Lunteren, The Netherlands, Nov. 20-21, 2013 Horvatovich, P., Current challenges in pre-processing of label-free LC-MS data of complex proteomics samples. Université de Strasbourg, France, April 25, 2013 Horvatovich, P., Towards a comprehensive LC-MS proteomics data processing platform. Skype presentation at 61st ASMS Conference on Mass Spectrometry and Allied Topics, Minneapolis, USA, 9-13 June, 2013 Horvatovich, P., msCompare: A framework for quantitative processing and assessment of LC-MS data. 1st International Conference on Profiling, Caparica, Portugal, Sept. 2-4, 2013 Horvatovich, P., C-HPP Wiki workshop. HUPO 2013 – 12th Annual World Congress, Yokohama, Japan, Sept. 14-18, 2013 Horvatovich, P., Update on Chromosome 5. Kyoto HUPO Initiative Assembly, Kyoto, Japan, Sept. 19, 2013 Merbel, N.C. van de, The value of an analytical result. MasterLab laboratory managers meeting. Hoofddorp, The Netherlands, May 15, 2013 Merbel, N.C. van de, LC-MS as a platform for the quantitative bioanalysis of biopharmaceutical proteins. FABIAN (the analytical challenge), Utrecht, The Netherlands, Nov. 7, 2013 Merbel, N.C. van de, The usefulness of LC-MS as a platform for protein quantification, from theory to practice. European Bioanalysis Forum, 6th Annual Open Symposium. Barcelona, Spain, Nov. 20, 2013


Merbel, N.C. van de, Blood is no plasma: failing long-term frozen stability results for cyclosporine A in diluted whole blood. European Bioanalysis Forum, 6th Annual Open Symposium. Barcelona, Spain, Nov. 21, 2013 Ongay, S., Analysis of biomolecules on surfaces. TA-COAST, Lunteren, The Netherlands, May 15, 2013 Wilffert, D., Quantitative UPLC – MS/MS of target proteins in serum. Spring meeting KNCV Werkgroep Scheidingsmethoden, Sectie Analytische Chemie, Leiden, The Netherlands, April 19, 2013 Poster presentations Bischoff, R., Dutch Biomarker Development Center. LSH Plaza meeting, Utrecht, The Netherlands, Jan. 31, 2013 Bischoff, R., Güzel, C., Govorukhina, N.I., Hoor, K. ten, Dekker, L.J.M., Hollema, H., Klip, H.G., Zee, A.G.J. van der, Luider, T.M., Cervix carcinoma proteomics: Biomarker discovery in tissue by laser microdissection with biomarker validation in serum. Proteomics Forum 2013, Berlin, Germany, March 17-21, 2013 Boichenko, A., Govorukhina, N., Zee, A. van der, Bischoff, R., 2D LC/MS separation of tryptic peptides from human serum proteins using reversed-phase, strong cation exchange, weak anion exchange and fused core fluorinated stationary phases. 39th International Symposium on High Performance Liquid Phase Separations and Related Techniques (HPLC 2013), Amsterdam, The Netherlands, June 16-20, 2013 Boichenko A.P., Govorukhina N., Zee A.G.J. van der, Bischoff R., Mass-spectrometry based targeted quantification of cervical cancer related proteins in human serum, Annual Meeting of the NWO/CW Studygroup Analytical Chemistry and COAST, the public-private partnership on Analytical Science & Technology, Lunteren, The Netherlands, Nov. 20-21, 2013 Bronsema, K., Bischoff, R., Merbel, N. van de, The role of internal standards in high-sensitivity protein quantifications with LC-MS/MS. 39th International Symposium on High Performance Liquid Phase Separations and Related Techniques (HPLC 2013), Amsterdam, The Netherlands, June 16-20, 2013 Bronsema, K., Bischoff, R., Merbel, N. van de, The role of internal standards in high-sensitivity protein quantifications with LC-MS/MS. European Bioanalysis Forum, 6th Annual Open Symposium. Barcelona, Spain, Nov. 20-22, 2013 Govorukhina, N., Güzel , C., Bruin, A.I. de, Hoor, K.A. ten, Boichenko, A.P., Klip, H.G., Zee, A.G.J. van der, Luider, Th.M., Bischoff, R., Laser microdissection and cervix carcinoma proteomics: translation of heat shock protein 90α as potential biomarker candidate from tissue to serum. MSACL, San Diego, USA, Feb. 9-13, 2013 Gül, T., Permentier, H.P., Bischoff, R., Method development for electrochemical synthesis of oxidative drug metabolites. ElCheMS (2nd International Workshop on Electrochemistry/Mass Spectrometry), Münster, Germany, May 23-24, 2013 Gül, T., Permentier, H.P., Bischoff, R., Optimization of reaction parameters for electrochemical oxidation of drug compounds with the Design of Experiments technique. Annual Meeting of the NWO/CW study group Analytical Chemistry and


COAST, the public-private partnership on Analytical Science & Technology, Lunteren, The Netherlands, Nov. 20-21, 2013 Güzel, C., Govorukhina, N., Hoor, K. ten, Dekker, L.J.M., Hollema, H., Klip, H.G., Zee, A.G.J. van der, Boichenko, A., Luider, Th.M., Bischoff, R., Quantitation of low levels of heat shock protein 90 in serum of cervical cancer patients by Selected Reaction Monitoring. ASMS, Minneapolis, USA, June 9-13, 2013 Güzel, C., Govorukhina, N., Hoor, K. ten, Dekker, L.J.M., Hollema, H., Klip, H.G., Zee, A.G.J. van der, Boichenko, A., Luider, Th.M., Bischoff, R., Cervix carcinoma proteomics: Biomarker discovery in tissue by laser microdissection, Proteomics Forum 2013, Berlin, Germany, March 17-21, 2013 Hoekman, B., Christin, C., Hoefsloot, H., Smilde, A., Breitling, R., Suits, F., Bischoff, R., Horvatovich, P., Critical assessment of LC-MS data pre-processing and feature selection methods for biomarker discovery in clinical proteomics. Proteomics Forum 2013, Berlin, Germany, March 17-21, 2013 Horvatovich, P.L., Chromosome-centric human protein project chromosome 5. HUPO 2013 – 12th Annual World Congress, Yokohama, Japan, Sept. 14-18, 2013 Mitra, V., Govorukhina, N., Zwanenburg, G., Smilde, A., Reijmers, T., Westra, I., Suits, F., Bischoff, R., Horvatovich, P., Experimental design for complex proteomics samples using ASCA. NPC 10th anniversary conference: 10 Years Progress in Proteome Biology, Utrecht, The Netherlands, Feb. 11-12, 2013 Ongay, S., Langelaar, M., Groothuis, G., Bischoff, R., Development of a new tissue fixative: towards facilitating proteomic analysis on fixated tissue. Annual Meeting of the NWO/CW study group Analytical Chemistry and COAST, the public-private partnership on Analytical Science & Technology, Lunteren, The Netherlands, Nov. 20-21, 2013 Prely, L., Oldenburger, A., Hermans, J., Paal, K., Castelli, R., Merbel, N.C. van de, Oosterhout, A.J.M. van, Overkleeft, H.S., Schmidt, M., Bischoff, R., Studying the MMP-9 – TIMP-1 protease-inhibitor system by activity-based enrichment and selected reaction monitoring (SRM) nano-LC-MS/MS. 39th International Symposium on High Performance Liquid Phase Separations and Related Techniques (HPLC 2013), Amsterdam, The Netherlands, June 16-20, 2013 Pruim, P., Hilhorst, M., Hendriks, G., Hillewaert, V., Vries, R. de, Verhaeghe, T., Merbel, N. van de, An improved LC-MS/MS method for the determination of artemether and dihydroartemisinin in human plasma. European Bioanalysis Forum, 6th Annual Open Symposium. Barcelona, Spain, Nov. 20-22, 2013 Rozeveld, D., Bischoff, R., Oosterhout, A. van, Heijink, I., ADAM10 plays a crucial role in house dust mite-induced release of chemokine ligand CCL20 by airway epithelium. American Thoracic Society International Conference 2013, Philadelphia, USA, May 17-22, 2013 Wilffert, D., Rodrigues dos Reis, C.R., Hermans, J., Govorukhina, N., Tushar, T., Jong, S. de, Quax, W.J., Merbel, N.C. van de, Bischoff, R., Quantitative, antibody-free LC-MS/MS analysis of recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in serum. 39th International Symposium on High Performance Liquid Phase Separations and Related Techniques (HPLC 2013), Amsterdam, The Netherlands, June 16-20, 2013


Wilffert, D., Rodrigues dos Reis, C.R., Hermans, J., Govorukhina, N., Tushar, T., Jong, S. de, Quax, W.J., Merbel, N.C. van de, Bischoff, R., Quantitative, antibody-free LC-MS/MS analysis of recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in serum. Annual Meeting of the NWO/CW study group Analytical Chemistry and COAST, the public-private partnership on Analytical Science & Technology, Lunteren, The Netherlands, Nov. 20-21, 2013 Yang, Y., Ongay, S., Kema, I., Bischoff, R., Specific enrichment of 3-nitrotyrosine–containing peptides for biomarker discovery. 39th International Symposium on High Performance Liquid Phase Separations and Related Techniques (HPLC 2013), Amsterdam, The Netherlands, June 16-20, 2013 Yuan, T., Permentier, H.P., Bruins, A.P., Bischoff, R., Modified electrodes applied in the investigation of drug metabolism. ElCheMS (2nd International Workshop on Electrochemistry/Mass Spectrometry), Münster, Germany, May 23-24, 2013 Zhang, T., Permentier, H.P., Bischoff, R., Specific enrichment method for electrochemically cleaved peptides. ElCheMS (2nd International Workshop on Electrochemistry/Mass Spectrometry), Münster, Germany, May 23-24, 2013 Zhang, T., Permentier, H.P., Bischoff, R., Development of a specific enrichment method for electrochemically cleaved peptides. Annual Meeting of the NWO/CW study group Analytical Chemistry and COAST, the public-private partnership on Analytical Science & Technology, Lunteren, The Netherlands, Nov. 20-21, 2013 Miscellaneous: Bischoff, R., Coordinator of the Division Medicinal Chemistry and Bioanalysis of the Groningen University Institute of Drug Exploration (GUIDE) Bischoff, R., Board of Examiners, TopMaster in Medical and Pharmaceutical Drug Innovation for the Graduate School of Medical Sciences (University of Groningen) Bischoff, R., Director: Mass Spectrometry Center of the Faculty of Mathematics and Natural Sciences (University of Groningen) Editorial Tasks Bischoff, R., Executive Editor, J. Chromatogr. B (Elsevier) Horvatovich, P.L., Editorial Board Member, J. Proteome Res. (ACS) Horvatovich, P.L. and Bischoff, R., invited editors of the book “Proteomics biomarker discovery and validation for clinical applications" published by the Royal Society of Chemistry of the United Kingdom Merbel, N.C. van de, Editorial Board Member, Bioanalysis (Future Science) Scientific Advisory Functions: Bischoff, R., Board Member, Dutch Proteomics Platform


Bischoff, R., Board Member, Working Group Pharmaceutical and Biomedical Analysis of the Royal Dutch Chemical Society (KNCV) Horvatovich, P., Secretary of the Dutch PhD student (AIO) Network Analytical Chemistry Merbel, N.C van de, Harmonization team leader of the Global Bioanalysis Consortium (GBC) Seminars Prof. Dr. Herbert Oberacher, Innsbruck Medical University, Innsbruck, Austria: Forensic applications of high resolution mass spectrometry. March 8, 2013 Prof. Dr. Manfred Wuhrer, VU University Amsterdam, Amsterdam, The Netherlands: Clinical glycomics of autoimmune diseases and cancer. May 7, 2013 Prof. Dr. Bernd Bodenmiller, University of Zurich, Switzerland: Mass cytometry to study single cell signaling in biology and disease. June 11, 2013 Awards Third price best poster competition at the European Bioanalysis Forum, 6th Annual Open Symposium, Barcelona, Spain, 20-22 November 2013: Bronsema, Bischoff, Merbel van de, The role of internal standards in high-sensitivity protein quantifications with LC-MS/MS. Agilent Best Poster Award (by the board of expert reviewers), 39th International Symposium on High Performance Liquid Phase Separations and Related Techniques (HPLC 2013), Amsterdam, The Netherlands, June 16-20, 2013: Wilffert, Reis, Hermans, Govorukhina, Tomar, de Jong, Quax, van de Merbel, Bischoff, Quantitative, Antibody-Free LC-MS/MS Analysis of Recombinant Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) in Serum.


Research: Funded Projects: Netherlands Proteomics Center II - Bioinformatics in proteomics (Topic E4) Project title: Quantitation, processing and classification algorithms for mass spectrometry (E 4.2) Principal Investigator: Prof. Dr. Peter Horvatovich Funding Period: 2009-2013 Netherlands Proteomics Center II – New separation and enrichment tools in proteomics (Topic: E1) Project title: Affinity Enrichment of Proteins and Peptides (E 1.3) Principal Investigator: Prof. Dr. Rainer Bischoff Funding Period: 2009-2013 NWO Centres for Systems Biology Research (CSBR) Systems Biology Centre for Energy Metabolism and Ageing Principal Investigator: Prof. Dr. Bert Groen (University Medical Center Groningen) Funding Period: 2010-2015 NWO-STW 11056 Innovative analytical methodologies for biopharmaceuticals Principal Investigator: Prof. Dr. Rainer Bischoff (University of Groningen) Funding Period: 2011-2015 Dutch Cancer Society (KWF) RUG-2011-5021 Biomarkers for cervical cancer: from discovery to the clinic Principal Investigator: Prof. Dr. Rainer Bischoff (University of Groningen) Funding Period: 2011-2015 NWO-ACTS/TA-COAST 053.21.104 Analysis of biomolecules on surfaces (BIOSURF) Principal Investigator: Prof. Dr. Rainer Bischoff (University of Groningen) Funding Period: 2012-2015 NWO-STW 11957 Electrochemistry – Mass Spectrometry (EC-MS) for proteomics and drug metabolism Principal Investigator: Prof. Dr. Rainer Bischoff (University of Groningen) Funding Period: 2012-2016 NWO-ECHO 711.012.006 Electrochemically-assisted redox enzyme reactors by cofactor immobilization Principal Investigator: Prof. Dr. Marco Fraaije (University of Groningen) Funding Period: 2012-2016


EU-COST Action CM1201 Biomimetic radical chemistry Principal Investigator: Prof. Dr. Chrys Chatgilialoglu (University of Bologna, Italy) Dutch representatives on the management team: Prof. Dr. Frank Dekker Prof. Dr. Rainer Bischoff Funding Period: 2012-2016 Chromosome-Centric Human Proteome Project (C-HPP) Principal Investigators: Prof. Dr. Young-Ki Paik (Yonsei University, Seoul) Prof. Dr. György Marko-Varga (Lund University, Sweden) Prof. Dr. William S. Hancock (Northeastern University, Boston, USA) Responsible scientists for Chromosome 5 (the “Dutch Chromosome”) Prof. Dr. Rainer Bischoff Prof. Dr. Peter Horvatovich Period: 2012-2022 SNN project T3041 Ontwikkeling van LC-MS/MS als platformtechnologie voor de bioanalyse van eiwitten Principal investigator: Prof. Dr. Nico C. van de Merbel Funding Period: 2013-2017 NWO-STW Perspectief program P12-04 Biomarker Development Center (Biomarker-DC) Principal investigator: Prof. Dr. Rainer Bischoff Co-investigators: Dr. Theo M. Luider & Dr. Arfan Ikram (Erasmus Medical Center, Rotterdam) Prof. Dr. Alain van Gool & Prof. Dr. Ron Wevers (Radboud University Medical Center, Nijmegen) Dr. Nick ten Hacken (University Medical Center Groningen) Funding Period: 2014-2019


Teaching Bachelor projects Nov. 19, 2012 – Feb. 1, 2013

Apr. 24 – June 28, 2013 Nov. 11 – Feb. 2014

Biostatistics (bachelors) March 25 – 22 April 2013 June 11 – July 15, 2013

FATEM Feb. 24, 2013 Biotechnology (masters) March 5, 2013 Industrial Bioanalysis (masters) March 4 – March 22, 2013 MFO (Medisch-Farmaceutisch Onderzoek) March 27, 2013 Proteomics/Genomics (bachelors) April 17 – May 4, 2013 Medical Genomics & Proteomics (bachelors) May 21 – June 10, 2013 Introduction to proteomics (Faculty of Pharmacy, University of Strasbourg)

April 24, 2013

TI-COAST course on Biomarkers (national master’s program)

April 27, 2013

Behavioural and Cognitive Neurosciences (international masters)

Nov. 12, 2013

Medical and Pharmaceutical Drug Innovation (TopMasters)

Nov. 22, 2013

Mass Spectrometry (open course) Nov. 4 – 5, 2013 Pharmaceutical Analysis C (bachelors) Sept. 2 – Oct. 11, 2013 Drug Development (masters) Sept. 9, 2013

P.L. Horvatovich, member of the ‘opleidingscommissie’ J.W. Meints, member of the ‘ontwikkelteam Farmacie’


Outlook Many colleagues and friends have contributed to another exciting year of research, teaching and last not least to shouldering many other tasks. This time I would like to thank especially Hjalmar Permentier and Jos Hermans, who were indispensable in organizing the move to the new facilities at the ERIBA research institute. 2014 will see the start of the Biomarker Development Center as well as the continuation of Biopharmaceuticals research line with renewed funding. The extended capabilities at the new facilities should allow us to establish new collaborations and to attract funding. I am particularly excited about the Medicinal Chemistry and Bioanalysis (MCB) program that promises already now to be a stimulus for research collaborations. Peter Horvatovich has taken the lead in the Chromosome-Centric Human Proteome Project and first concrete research activities are on the horizon albeit that funding is still pending. I want to take this opportunity to thank all co-workers for their excellent work in 2013 as well as the many collaborators in and outside the University of Groningen for pleasant and efficient collaborations.

Annual report 2013 140112 FINAL - University of Groningen · 2014-01-20 · Chemistry and...

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