Analytical Biochemistry & Interfaculty MS Center · Analytical Biochemistry group on the analysis of thyroid hormones and TRAIL. He returned to Italy in the fall to finish and defend

faculty of mathematics and natural sciences

department of pharmacy

Analytical Biochemistry & Interfaculty MS Center

Annual Report 2015 Prof. Dr. Rainer Bischoff Prof. Dr. Peter Horvatovich Dr. Hjalmar Permentier 04 February 2016

Analytical Biochemistry & Interfaculty MS Center › 2

Table of Contents Members of the Research Groups 4

Overview 5

Research Projects 6

PhD Projects 15

Scientific Output 17

Research Grants 23

Teaching 25

Outlook 26


Group Photo From left to right and back to front: Tao (Larry) Zhang, Tao Yuan, Nico van de Merbel (PRAHS), Daan Pouwels (UMCG), Wenxuan Zhang (UMCG), Marcel de Vries (UMCG), Hjalmar Permentier, Jos Hermans, Andres Gil-Quintero, Natalia Govorukhina, Peter Bults (PRAHS), Annie van Dam, Jan Willem Meints, Turan Gül, Frank Klont, Karin Wolters (UMCG), Mireille Wessels (UMCG), Vikthor Nijenhuis, Rainer Bischoff, Jolanda Meindertsma, Alienke van Pijkeren Not on photo: Margot Jeronimus-Stratingh, Peter Horvatovich, Jiaying Han

Head of Analytical Biochemistry Prof. Dr. Rainer Bischoff Phone: (+31)-50-363-3338 E-mail: [email protected] Website: www.biomac.nl

Head of Interfaculty MS Center Dr. Hjalmar Permentier Phone: (+31)-50-363-3262 E-mail: [email protected] Website: http://mscenter.webhosting.rug.nl/tiki-index.php


Members of the Research Groups: Staff Prof. Dr. Rainer Bischoff Prof. Dr. Peter Horvatovich Prof. Dr. Nico van de Merbel (PRAHS) Dr. Natalia Govorukhina Jos Hermans Jan Willem Meints Jolanda Meindertsma (secretary; 0.4 fte) Interfaculty Mass Spectrometry Centre Dr. Hjalmar Permentier Annie van Dam (0.5 fte) Margot Jeronimus-Stratingh (0.5 fte) Marcel de Vries (UMCG) Post-doctoral researchers Dr. Karin Wolters (UMCG) Dr. Daan Pouwels (UMCG, since Dec. 01, 2015) Ph.D. students Kees Bronsema (PRAHS) (thesis defended on Oct. 30, 2015) Lorenza Franciosi (thesis defended on Nov. 27, 2015) Daniël Wilffert (thesis defense planned for Feb. 26, 2016) Turan Gül Tao Yuan Tao (Larry) Zhang Jorge Andres Gil Quintero Frank Klont Jiaying Han Peter Bults (start Jan. 2015) (PRAHS) Wenxuan Zhang (UMCG) (start Nov. 01, 2015) Research Students Huseyin Arici Jitse Veenstra Neeltje Wijma Angela Asselman Wenxuan Zhang Alienke van Pijkeren Karel Gebrands Štěpánka Zvěřinová Arne Roeters Vikthor Nijenhuis Visiting scientists Annalisa d'Urzo, University of Bologna (Italy) Dr. Zhengjin Jiang, Jinan University, Guangzhou (China) Liu Chusheng, Jinan University, Guangzhou (China) Riccardo Donzelli, University of Pisa (Italy) Prof. Dr. Dirk-Jan Reijngoud (UMCG)


Overview 2015

The integration between the Analytical Biochemistry Group and the Interfaculty Mass Spectrometry Center (IMSC) was completed in 2015 and the joint operation runs smoothly. The collaboration with PRA Health Sciences (PRAHS) was continued and further consolidated not the least through the PhD awarded to Kees Bronsema on Oct. 30, 2015 with Nico van de Merbel as first promotor. The output from this collaboration amounts already to 17 joint author publications since 2012 and a joint grant from the Samenwerkingsverband Noord Nederland (SNN). The professorship by special appointment of Nico van de Merbel was recently prolonged for another 5 years.

The Biomarker Development Center (http://biomarkerdevelopmentcenter.nl/) went into its first year of full operation with all positions filled by September 2015 in the 3 centers. Please visit the website and check the news including the recently added video presenting biomarker research at the Analytical Biochemistry group. The new equipment was put into operation and notably the Q-Exactive Plus Orbitrap is in full use for proteomics applications at the IMSC. New activities were initiated notably by Peter Horvatovich, who embarked on a number of proteogenomics projects in collaboration with colleagues from the GRIAC research institute at the UMCG and Viktor Guryev from the European Research Institute for the Biology of Ageing (ERIBA). It is encouraging to see that Peter received a number of grants in 2015 to support his activities in Computational Mass Spectrometry and Proteogenomics.

The IMSC continues to provide a wide range of mass spectrometry services and scientific support, with an increasingly strong focus on ‘omics’ applications, in particular proteomics. The large user base has expanded further in 2015, notably with UMCG research groups. The experienced team of operators worked hard and successfully to meet this demand, resulting in several co-authored publications with IMSC users. Another notable development is the increasing need for in-depth analysis of complex ‘omics’ data sets, which remains an important challenge for the coming year.

Our work as partner of the worldwide C-HPP program of the Human Proteome Organization (HUPO; (http://www.c-hpp.org/) continued in 2015 driven to a large extend by collaborative activities of Peter Horvatovich resulting in two papers on ''missing proteins'' and a new way of generating large numbers of internal standards for quantitative, targeted proteomics. Peter co-authored another communication on the use of Galaxy for multi-omic data analysis published in Nat. Biotechnol. In recognition of his contributions to the C-HPP network, he was nominated PI of the chromosome 5 team. In further recognition of his outstanding contributions to proteomics-related bioinformatics, Peter was appointed as honorary scientist at the Department of Translational Medicine and Centre of Excellence in Biological and Medical Mass Spectrometry at Lund University (Sweden).

We had a number of visiting scientists in 2015, which enriched and enlivened the atmosphere in the group. Zhengjin Jiang (professor at Jilin University in Guangzhou, China) visited us for 6 months together with his PhD student Liu Chusheng. Zhengjin is an expert in the development of monolithic HPLC columns and notably the immobilization of phospholipids as stationary phases. We keep collaborating with his group after his return to China on a number of applications in the proteomics and metabolomics field and hope to publish this work together in 2016. Annalisa d'Urzo stayed with us for most of the year working on a method to analyse histone acetylation in collaboration with the group of Frank Dekker. She returned to Italy just before Christmas to finish and defend her PhD thesis. Riccardo Donzelli from the University of Pisa (Italy) stayed with us and worked in the group of Ido Kema (UMCG) and the Analytical Biochemistry group on the analysis of thyroid hormones and TRAIL. He returned to Italy in the fall to finish and defend his PhD thesis. I hope you'll enjoy reading this Annual Report and wish you a successful year 2016. Please contact me in case you see possibilities for collaborations. I would be happy to discuss them with you.


Research Projects

1. Cervical Cancer Biomarkers The cervical cancer project made again significant progress in 2015 in close collaboration with the groups of Ate van der Zee (UMCG) and Theo Luider (Erasmus University Medical Center, Rotterdam). Coworkers that were actively involved in this project were Natalia Govorukhina, Alexander Boychenko (Groningen & Munich) and Coskun Güzel (Rotterdam). The project received funding from the Dutch Cancer Society (KWF). Project Description Cervical carcinoma is the second most frequent carcinoma in women worldwide, while in developing countries cervical carcinoma is the most frequent carcinoma in women. In this project, we are developing new LC-MS/MS approaches to detect biomarkers for the early diagnosis and prognosis of cervical cancer based on serum and tissue analyses. Work on serum-based biomarker panel continued and the panel was refined to comprise 4 proteins. Immunoassays of these 4 proteins leads to an excellent specificity and sensitivity in discriminating serum from healthy women (healthy and CIN1 considered healthy in a clinical sense) and CIN2/3 or worse (see Figure). The panel is currently the subject of a patent application. Together with our colleagues in Rotterdam, we are also following up on the targeted tissue analysis by laser-guided microdissection, which led to a number of highly interesting candidates notably for gaining a better understanding of the mechanism that leads from an infection with high-risk HPV to cervical cancer.

ROC curve depicting the sensitivity and specificity of a serum-based 4-protein biomarker panel for discriminating healthy/CIN1 from CIN2/3 or worse. The score is calculated using a linear logistic regression algorithm.

It is one of our aims to develop a handheld device for the early diagnosis of CIN2/3 or worse for home-testing in developing countries, which is one of the focal points of the Gates Foundation.

Sensitivity = 100%

Specificity = 93.75%


2. Computational Mass Spectrometry (group Horvatovich) This research line is carried out by two PhD students Vikram Mitra and Jiaying Han under the supervision of Peter Horvatovich. The second publication of Vikram presenting a multivariate evaluation of human blood peptide profiles obtained with an experimental design strategy is currently under revision. Peter Horvatovich is further actively involved in the activities of the Chromosome Centric Human Proteome Project as PI of the Chromosome 5 team as of January 2016 and Secretary General of the Chromosome Centric Human Proteome Project. C-HPP is an initiative of the Human Proteome Organization (HUPO). This activity resulted in a Consortium perspective paper summarizing novel technologies to identify missing proteins and a paper describing the use of in vitro transcription/translation to identify missing proteins in a special issue of the Journal of Proteome Research on the C-HPP program. The research line on Imaging Mass Spectrometry (IMS) and targeting drug encapsulating metallocages is being pursued by Jiaying Han (PhD project supported by a CSC scholarship). This project has the goal to develop a novel, sensitive, targeted IMS approach using photo-cleavable mass tags in collaboration with Angela Casini (Cardiff University, UK) and Hjalmar Permentier.

Proteogenomics data analysis integrating mRNA and proteomics data form another important research line. Data integration is based on constructing patient- and sample-specific protein sequence databases for LC-MS/MS-based peptide/protein identification using mRNA sequence data measured in the same sample. This project was initiated in collaboration with Victor Guryev (ERIBA, UMCG) and with participations of colleagues from the Groningen Research Institute on Asthma and COPD (GRIAC; Corry-Anke Brandsma, Maarten van de Berge, Dirkje Postma and Wim Timens) working at the Pulmonology and Pathology Departments of the UMCG. The project has the aim to perform proteogenomics analysis of human lung tissue and patient derived human fibroblast cells of Chronic Obstructive Pulmonary Disease (COPD) patients and controls to identify patient-specific and disease-related protein forms leading to the molecular mechanisms underlying COPD. The proteogenomics project is supported by a seeding grant from ERIBA/UMCG.

A new collaboration has been established in the area of Head and Neck Cancer (UMCG) in collaboration with Gyorgy Halmos to study proteome profile differences between young and elderly head and neck cancer patients. A pilot project was started to benchmark various protein extraction approaches using three different types of human tissues. Sample acquisition to compare 20 young and 20 elderly laryngeal squamous cell carcinomas and healthy tissues is ongoing and will be analysed this year using a proteogenomics approach.

A PhD project has been awarded from the Data Science and System Complexity theme of the Faculty of Science with partial support from Erik Frijlink (Dept. of Pharmacy) with the goal to develop a Bayesian Network and Machine Learning analysis approach to identify molecular subnetworks in molecular profiles and clinical metaparameters. This project includes collaboration of multiple groups such as Victor Guryev (genomics), Head and Neck Department (Gyorgy Hlamos), statistics (Marco Grzegorzyk), pulmonology (GRIAC) and medical oncology (Kathrin Thedieck).

Two other projects received funding at the end of 2015. PROMETOV, a TRANSCAN project, has the aim to define the heterogeneity of primary and metastatic ovarian tumors and involves collaborations with several European partners from Germany, Turkey, UK and Estonia and one local partner (Kathrin Thedieck). The second awarded project is funded by the Qatar National Research Foundation (QNRF) and has the goal to identify molecular markers for foodborne mycotoxin intoxication of the population in Qatar.

To strengthen the collaboration between the Centre of Excellence in Biological and Medical Mass Spectrometry at Lund University (Sweden), Peter Horvatovich received


an honorary position to perform high-throughput data analysis of LC-MS/MS proteomics data. 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 called 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 an understanding of the structure of the data and the analytical procedures through which artefacts may have been generated. We are collaborating on the implementation of a comprehensive 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. This collaboration resulted in a perspective paper in Nature Biotechnology. The collaboration with Frank Suits at the IBM Watson Research Center is continuing to further develop the Threshold Avoiding Proteomics Pipeline (TAPP) to assign peptide identities to isotopologue peaks in proteomics data. This work was supported by a very talented student Karel Gerbrands. Jiaying Jan progressed with finding the appropriate conditions to bioconjugate palladium-based metallocages to peptides for targeted drug delivery. She is also finalising a review on MALDI imaging.

Vikram Mitra is moving towards finalizing and defending his thesis in 2016 based on published work on the effect of orthogonal separations on the time alignment of LC-MS data and the assessment of the importance of pre-analytical factors on quantitative molecular profiles of complex shotgun proteomics samples. The work is performed in close collaboration with colleagues at the University of Amsterdam (Age Smilde, Gooitzen Zwanenburg).

Multiomics data integration to explore the molecular mechanism of COPD in human lung tissue using mRNAseq and proteomics data analysed in a combined proteogenomics workflow. COPD is a complex disease with multiple clinical phenotypes such as emphysema, chronic bronchitis and mucus hypersecretion. A better understanding of the different

underlying molecular mechanisms is needed to identify the key protein actors of COPD hopefully leading to better patient classification and treatment options.


3. Electrochemistry-Mass Spectrometry The different lines of this project are run in close collaboration between the Analytical Biochemistry group & the Interfaculty Mass Spectrometry Center with further collaborations at the Biochemistry/Biotechnology group at the University of Groningen (Marco Fraaije) and the BIOS Lab-on-a-chip group of the University of Twente (Mathieu Odijk, Wouter Olthuis, Albert van den Berg). The major lines of the project are the electrochemical conversion of drug molecules into metabolites and the electrochemical cleavage of peptides and proteins. Project Description Work on the electrochemical cleavage of peptides and proteins (Larry Zhang) has progressed significantly in 2015 and is now at a stage where applications to larger peptides and proteins are being investigated, notably in collaboration with Floris van den Brink (UTwente) and his specifically developed microfluidic chip with a boron-doped diamond working electrode. A recent discovery (patent application in preparation) on how to improve the chemical tagging of the spirolactone moiety of electrochemically cleaved peptides and the integration of the electrochemical disulfide bond reduction step (collaboration with UTwente and Antec Leyden) constitute important steps towards a fully applicable protein analysis system.

The semi-preparative electrochemical synthesis of Phase-I drug metabolites (Turan Gül) has advanced thanks to significant progress in understanding the mechanism of N-dealkylation reactions. Systematic optimization of the reaction parameters in a Design of Experiment (DoE) approach allowed us to suppress the predominant N-dealkylation reaction at acidic pH values during the direct electrochemical conversion of lidocaine and promote other phase-I metabolism-like conversions (manuscript in preparation).

LC-MS in the SRM mode of lidocaine (235/86) at a) pH 3 and of the N-dealkylation product of lidocaine (207/58) after EC-mediated oxidation for 30 min using a glassy carbon electrode and 1.5 V; b) at pH 3, c) at pH 1.5, d) at pH 0.5 (TFA), and e) at pH 0.5 (H2SO4).1

Our collaboration with the Fraaije group has further allowed to mimic human phase-I drug metabolism reactions catalyzed by FAD-dependent monooxygenases (FMOs)

— 1 Gül, T., Bischoff, R., and Permentier, H. P. (2015) Optimization of reaction parameters for the electrochemical oxidation of lidocaine

with a Design of Experiments approach. Electrochimica Acta 171, 23-28

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using recombinant, bacterial FMOs resulting in enantioselective conversions of xenobiotics into their sulfoxide metabolites.

The work on improving conversion yields has also advanced considerably notably due to the discovery of specific properties of nano-porous gold surfaces (patent application in preparation). We are continuing our collaboration with UTwente on spectroscopic studies of the modified surfaces, which resulted in an EC-SERS study of a hemin-modified nanostructured gold electrode.2 We will apply for further funding to extend this work, as we believe that a better understanding of the surface phenomena is crucial to improving reaction yields and selectivity. The project lines are funded by the Dutch Technology Foundation (STW), the Dutch Research Organization (NWO, ECHO grant, Fraaije) and the Chinese Scholarship Council (CSC, Larry Zhang).

— 2 Yuan, T.; Le Thi Ngoc, L.; van Nieuwkasteele, J.; Odijk, M.; van den Berg, A.; Permentier, H. P.; Bischoff, R.; Carlen, E. T. An in situ

Surface-Enhanced Raman Spectroelectrochemical Analysis System with Hemin Modified Nanostructured Gold Surface. Anal Chem 2015,

87, 2588-2592.


4. Proteomics by targeted mass spectrometry

Expertise in targeted LC-MS/MS for proteomics analyses was initially built up as part of projects related to the Systems Biology Center for Energy Metabolism and Ageing Research (SBC-EMA). Karin Wolters established quantitative protein analysis methodology based on protein-specific peptides by LC-MS/MS in the selected reaction monitoring (SRM) mode. Quantitation of these proteins is being done by addition of isotopically labeled standards in the form of synthetic concatamers created by the combination of all targeted peptides into one synthetic protein (QconCAT technology). We currently apply these methods to a wide range of biology projects including protein targets related to fatty acid metabolism, triglyceride hydrolysis and atherosclerosis (coll. van Kuivenhoven and Groen), protein classes like the copper metabolism MURR1 domain (COMMD) protein family (coll. van de Sluis), mitochondrial proteins (coll. Bakker) and nuclear pore complexes (coll. Veenhoff). Project Description The figure below shows the use of the isotopically labeled standards to check effects of plasma sample preparation. Albumin can be depleted via specific protein precipitation conditions which keep albumin in solution, while precipitating the majority of the proteins (Anal. Chem. 2014, 86, 8336−8343) representing a fast depletion method (as can be seen from the gel analysis shown on the left side). However, MS analysis of one of the bands in the non-precipitated fraction (highlighted by the green box) shows that one of in the intended protein targets (ApoE) is co-depleted. MS results for the ApoE peptide FWDYLR are shown on the right side. The isotopically labeled peptide of ApoE (blue peak) is used to calculate the concentration of the endogenous peptide (red peak), and in this way yielding quantitative information about this protein.

Treatment of plasma samples. Plasma was loaded as such or after precipitating the majority of proteins (prec) while albumin remains in the supernatant (not prec). The gel region boxed in green was analysed by targeted proteomics and shown to contain ApoE, one of the target protein, namely ApoE.


5. Metabolite analysis Andres Gil (PhD student) continued the analysis of energy metabolites by LC-

MS/MS notably studying the effect of pre-analytical factors on metabolite stability and interconversion. Next to this work we followed a novel metabolite in serum and showed that it is related to mortality due to heart failure (collaboration with Peter van der Meer, UMCG) as well as initiating work on lipidomics in collaboration with Dirk-Jan Reijngoud (UMCG) and Wenxuan Zhang (PhD student that started in November 2015). Projects are funded by a grant from the Columbian Science, Technology and Innovation Department – COLCIENCIAS (to Andres Gil) and a grant on Systems Medicine to Dirk-Jan Reijngoud.

Project Description

Our work on pre-analytical factors showed that nucleotide triphosphates

interconvert into the di- and the mono-phosphates upon 'hot ethanol extraction', a widely used procedure to extract metabolites from biological samples due to the instant inhibition of enzymatic activity. Metabolite interconversion cannot be corrected for by the use of stable-isotope-labelled internal standards, commonly employed in LC-MS.

Degradation and interconversion of (A) ATP, (B) GTP, (C) UTP, and (D) CTP under the

conditions of a boiling ethanol extraction. The mixtures were incubated at 95°C under shaking for 0, 3, 6, 9, 12, and 15 min to follow the reactions. Chromatographic separation was achieved in the HILIC mode and metabolites were measured by high-resolution mass spectrometry. The statistical significance of differences between groups was evaluated by one-way ANOVA. Differences between means were assessed using the Newman–Keuls multiple comparisons post-test and significance at the 5% level (p <0.05). Results are expressed as the mean ± SD of the percentage of interconversion from tri-phosphates to di- and mono-phosphates and statistically significant differences are indicated by different superscript letters.3

— 3 Gil, A., Siegel, D., Permentier, H., Reijngoud, D.-J., Dekker, F., and Bischoff, R. (2015) Stability of energy metabolites—An often

overlooked issue in metabolomics studies: A review. Electrophoresis 36, 2156-2169


6. Biopharmaceuticals Our activities in the wider area of biopharmaceuticals continued unabated in 2015, thanks to the efficient collaboration with PRA Health Sciences (Nico van de Merbel) with funding from the Samenwerkingsverband Noord Nederland (SNN). Our work on TRAIL was finalized in August 2015 with the departure of Daniel Wilffert, who moved on to a position in industry (thesis defence scheduled for February 26, 2016). There were many exciting results in 2015 resulting in 5 joint publications. What stands out is the work on anti-drug antibodies by Kees Bronsema, who defended his thesis on October 30, 2015, results on the in vivo biotransformation of Trastuzumab by Peter Bults (joint PhD student with PRAHS) and the high-sensitivity analysis of endogenous TRAIL in sputum and saliva by Daniel Wilffert. We further continued our collaboration with the groups of Ido Kema and Daan Touw (both UMCG) in the fields of biomarkers and biopharmaceuticals. Project Description

Protein therapeutics or “biopharmaceuticals” are becoming the major class of pharmaceuticals to address unmet medical needs in the fields of oncology, auto-immune disorders and many other fields of major relevance. While biopharmaceuticals are scrupulously characterized prior to their approval by regulatory authorities, little to nothing is known about their biotransformation in vivo and the consequences for their activity, efficacy and possible side reactions. In a recent collaborative effort we studied Trastuzmab after its administration to breast cancer patients and found an in vivo biotransformation that may well have a major effect on efficacy. This is, to our knowledge, the first of such a study but we are sure that many more will follow.

LC-MS/MS and ELISA results in plasma obtained from a breast cancer patient on long-term treatment with trastuzumab. LC-MS/MS concentrations obtained for peptides FTISADTSK (total trastuzumab), IYPTNGYTR (non-deamidated trastuzumab), IYPTDGYTR (deamidated trastuzumab) and IYPTisoDGYTR (deamidated, inactive trastuzumab).4 It is interesting to note that the widely used ELISA assay requires an NG sequence at both complementarity-determining regions to generate a signal.

— 4 Bults, P., Bischoff, R., Bakker, H., Gietema, J. A., and van de Merbel, N. C. (2015) LC-MS/MS-based monitoring of in vivo protein

biotransformation: quantitative determination of trastuzumab and its deamidation products in human plasma. Anal Chem, in press

(10.1021/acs.analchem.5b04276)

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7. COPD Biomarkers

Projects in the Biomarker Development Center (BDC; http://biomarkerdevelopmentcenter.nl/) got going in 2015. The two projects in Groningen focus on prioritizing biomarkers for Chronic Obstructive Pulmonary Disease (COPD) and on developing high-throughput methodology for MALDI-TOF mass spectrometry. The prioritization work was driven by Sara Ongay and Nick ten Hacken (UMCG) and resulted in a recently submitted review article on the topic. Out of this work came the decision to focus on the soluble Receptor for Advanced Glycation Endproducts (sRAGE) as our first candidate for validation. Coincidently the COPD Biomarker Qualification Consortium (CBQC) of the US-based COPD Foundation also selected this marker as their next candidate for qualification with the FDA and we were asked to participate in developing a validated method for sRAGE. This activity is now ongoing with high priority and driven by Daan Pouwels (postdoc UMCG).

As part of our earlier work on COPD biomarkers, we continued work on desmosine and isodesmosine as potential biomarkers for elastin breakdown in the lung, due to emphysema development. Analysis of urine samples from the ECLIPSE study showed however, that the use of these biomarkers is hampered by a number of confounding factors, such as age and body mass index (BMI) and that care must be exercised to take these factors into account before drawing conclusions about urinary desmosine/isodesmosine levels and emphysema development.

Independent variables

Dependent variable: lnDES

β p-value

Age (year) 0.350 2.75 E-12

Gender (male/female) 0.301 4.64 E-10

BMI (kg/m2) 0.121 0.012

Current smoking (versus never smokers) 0.436 7.97 E-9

Former smoking (versus never smokers) 0.280 1.59 E-4

Multiple linear regression analysis of parameters influencing urinary desmosine levels in more than 300 urine samples from participants of the ECLIPSE study. The standardized coefficient (β) and corresponding regression significance (p-value) are shown.5

— 5 Sara Ongay, Marijke Sikma, Peter Horvatovich, Jos Hermans, Bruce E. Miller, Nick H.T. ten Hacken, Rainer Bischoff , Free urinary

desmosine and isodesmosine as COPD biomarkers: the relevance of confounding factors; J. COPD Foundation (accepted)


Ph.D. projects: Lorenza 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 Promotor: Prof. Dr. Rainer Bischoff Start: February 2008 Defended on Nov. 27, 2016 Vikram Mitra Quantitation, processing and classification algorithms for mass spectrometry Promotor: Prof. Dr. Peter Horvatovich Start: April 2009 Kees Bronsema (PRAHS) Quantitative determination of biopharmaceuticals in biological fluids using LC-MS based techniques Promotor: Prof. Dr. Nico van de Merbel Start: September 2010 Defended on Oct. 30, 2015 Daniel Wilffert Analysis of Biopharmaceuticals by LC-MS/MS Promotors: Prof. Dr. Rainer Bischoff Start: August 2011 Defence date: Feb. 26, 2016 Tao (Larry) Zhang (CSC scholarship) LC-Electrochemistry - Mass Spectrometry in Protein Chemistry Promotors: Prof. Dr. Rainer Bischoff Start: September 2012 Turan Gül Electrochemistry – Mass Spectrometry (EC-MS) for Drug Metabolism Promotor: Prof. Dr. Rainer Bischoff Start: September 2012 Tao Yuan Electrochemistry combined with mass spectrometry to study drug metabolism Promotor: Prof. Dr. Rainer Bischoff Start: October 2012 Andres Gil (Colciencias) Stability of Energy Metabolites: An Approach Towards Delivering Reliable and Valid Quantitative Data for Metabolomics Studies Promotor: Prof. Dr. Rainer Bischoff Start: February 2014


Frank Klont Biomarker validation for COPD by high-throughput sample preparation and MALDI-MS/MS mass spectrometry Promotor: Prof. Dr. Rainer Bischoff Start: September 2014 Jiaying Han (CSC scholarship) Multiplex targeted imaging of biomolecules in tissue with high spatial resolution using laser desorption/ionisation mass spectrometry Promotor: Prof. Dr. Peter Horvatovich Start: October 2014 Peter Bults (PRAHS) Bioanalysis of proteins Promotor: Prof. Dr. Nico van de Merbel Start: January 2015 Wenxuan Zhang (UMCG) Lipidomics in Systems Medicine Promotor: Dirk-Jan Reijngoud Start: November 2015


Scientific Output (accepted on Feb. 04, 2016) Scientific publications Peer-reviewed

1. Baas, B., Poddar, H., Geertsema, E.M., Rozeboom, H.J., de Vries, M.P., Permentier, H.P., Thunnissen, A.W., and Poelarends, G.J. (2015) Functional and structural characterization of an unusual cofactor-independent oxygenase. Biochemistry 54, 1219-1232

2. Bischoff, R., Permentier, H., Guryev, V., and Horvatovich, P. (2015) Genomic variability and protein species – improving sequence coverage for proteogenomics. Journal of Proteomics (http://dx.doi.org/10.1016/j.jprot.2015.09.021)

3. Blok, J.L., Li, K., Brodmerkel, C., Horvátovich, P., Jonkman, M.F., Horváth, B. (2015) Ustekinumab in hidradenitis suppurativa: clinical results and a search for potential biomarkers in serum. Br. J. Dermatol. (http://dx.doi: 10.1111/bjd.14338)

4. Boekel, J., Chilton, J. M., Cooke, I. R., Horvatovich, P.L., Jagtap, P.D., Kall, L., Lehtio, J., Lukasse, P., Moerland, P.D., and Griffin, T.J. (2015) Multi-omic data analysis using Galaxy. Nat Biotechnol 33, 137-139

5. Bronsema, K.J., Bischoff, R., Bouche, M.-P., Mortier, K., and van de Merbel, N.C. (2015) High-sensitivity quantitation of a Nanobody® in plasma by single-cartridge multidimensional SPE and ultra-performance LC–MS/MS. Bioanalysis 7, 53-64

6. Bronsema, K.J., Bischoff, R., Pijnappel, W.W.M.P., van der Ploeg, A.T., and van de Merbel, N.C. (2015) Absolute quantification of the total and antidrug antibody-bound concentrations of recombinant human α-glucosidase in human plasma using protein G extraction and LC-MS/MS. Anal Chem 87, 4394-4401

7. Bults, P., Bischoff, R., Bakker, H., Gietema, J.A., and van de Merbel, N.C. (2015) LC-MS/MS-based monitoring of in vivo protein biotransformation: quantitative determination of trastuzumab and its deamidation products in human plasma. Anal Chem (10.1021/acs.analchem.5b04276)

8. Bults, P., van de Merbel, N.C., and Bischoff, R. (2015) Quantification of biopharmaceuticals and biomarkers in complex biological matrices: A comparison of liquid chromatography coupled to tandem mass spectrometry and ligand binding assays. Expert Review of Proteomics 12, 355-374

9. Gil, A., Siegel, D., Permentier, H., Reijngoud, D.-J., Dekker, F., and Bischoff, R. (2015) Stability of energy metabolites—An often overlooked issue in metabolomics studies: A review. Electrophoresis 36, 2156-2169

10. Gul, T., Bischoff, R., and Permentier, H.P. (2015) Optimization of reaction parameters for the electrochemical oxidation of lidocaine with a Design of Experiments approach. Electrochimica Acta 171, 23-28

11. Gul, T., Bischoff, R., and Permentier, H.P. (2015) Electrosynthesis methods and approaches for the preparative production of metabolites from parent drugs. TrAC Trends in Analytical Chemistry 70, 58-66

12. Heijink, I. H., Rozeveld, D., van der Heide, S., van der Bij, W., Bischoff, R., van Oosterhout, A.J., and van der Toorn, M. (2015) Metalloproteinase profiling in lung transplant recipients with good outcome and bronchiolitis obliterans syndrome. Transplantation 99, 1946-1952

13. Horvatovich, P., Lundberg, E.K., Chen, Y.J., Sung, T.Y., He, F., Nice, E.C., Goode, R.J., Yu, S., Ranganathan, S., Baker, M.S., Domont, G.B., Velasquez, E., Li, D., Liu, S., Wang, Q., He, Q.Y., Menon, R., Guan, Y., Corrales, F.J., Segura, V., Casal, J.I.,


Pascual-Montano, A., Albar, J.P., Fuentes, M., Gonzalez-Gonzalez, M., Diez, P., Ibarrola, N., Degano, R.M., Mohammed, Y., Borchers, C.H., Urbani, A., Soggiu, A., Yamamoto, T., Archakov, A.I., Ponomarenko, E., Lisitsa, A. V., Lichti, C.F., Mostovenko, E., Kroes, R.A., Rezeli, M., Vegvari, A., Fehniger, T.E., Bischoff, R., Vizcaino, J.A., Deutsch, E.W., Lane, L., Nilsson, C.L., Marko-Varga, G., Omenn, G. S., Jeong, S.K., Cho, J.Y., Paik, Y.K., and Hancock, W.S. (2015) A quest for missing proteins: update 2015 on chromosome-centric human proteome project. J Proteome Res 14, 3415-3431

14. Horvatovich, P., Vegvari, A., Saul, J., Park, J.G., Qiu, J., Syring, M., Pirrotte, P., Petritis, K., Tegeler, T.J., Aziz, M., Fuentes, M., Diez, P., Gonzalez-Gonzalez, M., Ibarrola, N., Droste, C., De Las Rivas, J., Gil, C., Clemente, F., Hernaez, M.L., Corrales, F.J., Nilsson, C.L., Berven, F.S., Bischoff, R., Fehniger, T.E., LaBaer, J., and Marko-Varga, G. (2015) In vitro transcription/translation system: A versatile tool in the search for missing proteins. J Proteome Res 14, 3441-3451

15. Janssens, G.E., Meinema, A.C., González, J., Wolters, J.C., Schmidt, A., Guryev, V., Bischoff, R., Wit, E.C., Veenhoff, L.M., and Heinemann, M. (2015) Protein biogenesis machinery is a driver of replicative aging in yeast. eLife, e08527

16. Krzek, M., van Beek, H.L., Permentier, H.P., Bischoff, R., and Fraaije, M.W. (2016) Covalent immobilization of a flavoprotein monooxygenase via its flavin cofactor. Enzyme and Microbial Technology 82, 138-143

17. Matusiak, N., Castelli, R., Tuin, A.W., Overkleeft, H.S., Wisastra, R., Dekker, F.J., Prely, L.M., Bischoff, R.P., van Waarde, A., Dierckx, R.A., and Elsinga, P.H. (2015) A dual inhibitor of matrix metalloproteinases and a disintegrin and metalloproteinases, [18F]FB-ML5, as a molecular probe for non-invasive MMP/ADAM-targeted imaging. Bioorg Med Chem 23, 192-202

18. Matusiak, N., van Waarde, A., Rozeveld, D., van Oosterhout, A. M., Heijink, I., Castelli, R., Overkleeft, H., Bischoff, R., Dierckx, R. J. O., and Elsinga, P. (2015) MicroPET Evaluation of a Hydroxamate-Based MMP Inhibitor, [18F]FB-ML5, in a Mouse Model of Cigarette Smoke-Induced Acute Airway Inflammation. Molecular Imaging and Biology 17, 680-687

19. Niu, X., de Graaf, I.A., Langelaar-Makkinje, M., Horvatovich, P., and Groothuis, G.M. (2015) Diclofenac toxicity in human intestine ex vivo is not related to the formation of intestinal metabolites. Arch Toxicol 89, 107-119

20. Post, S., Rozeveld, D., Jonker, M., Bischoff, R., van Oosterhout, A., and Heijink, I. (2015) ADAM10 mediates the house dust mite-induced release of chemokine ligand CCL20 by airway epithelium. Allergy, (http://dx.doi.org/10.1111/all.12730)

21. Ruokolainen, M., Gul, T., Permentier, H., Sikanen, T., Kostiainen, R., and Kotiaho, T. (2016) Comparison of TiO2 photocatalysis, electrochemically assisted Fenton reaction and direct electrochemistry for simulation of phase I metabolism reactions of drugs. European Journal of Pharmaceutical Sciences 83, 36–44

22. Wang, X., Zhang, Y., Nilsson, C.L., Berven, F. S., Andren, P.E., Carlsohn, E., Horvatovich, P., Malm, J., Fuentes, M., Vegvari, A., Welinder, C., Fehniger, T.E., Rezeli, M., Edula, G., Hober, S., Nishimura, T., and Marko-Varga, G. (2015) Association of chromosome 19 to lung cancer genotypes and phenotypes. Cancer Metastasis Reviews 34, 217-226

23. Wilffert, D., Bischoff, R., and van de Merbel, N.C. (2015) Antibody-free workflows for protein quantification by LC–MS/MS. Bioanalysis 7, 763-779

24. Yuan, T., Le Thi Ngoc, L., van Nieuwkasteele, J., Odijk, M., van den Berg, A., Permentier, H.P., Bischoff, R., and Carlen, E.T. (2015) An in situ surface-enhanced raman spectroelectrochemical analysis system with hemin modified nanostructured gold surface. Anal Chem 87, 2588-2592


25. Yuan, T., Permentier, H., and Bischoff, R. (2015) Surface-modified electrodes in the mimicry of oxidative drug metabolism. TrAC Trends in Analytical Chemistry 70, 50-57

Other dissemination activities

Bischoff, R., Bridging the biomarker gap. How to bring better diagnostic tests to the market to benefit patients. The Analytical Scientist, issue 29, June 2015, pp. 18-19

Bischoff, R., Karst, U., Electrochemistry-mass spectrometry: Fundamentals and applications in pharmaceutical and environmental sciences. Editorial, Trends Anal. Chem. 70 (2015) 3

Merbel, N.C. van de, Advances in liquid chromatography–tandem mass spectrometry. (LC–MS–MS)-based quantitation of biopharmaceuticals in biological samples. LC-GC Europe, special issue Advances in Biopharmaceutical Analysis, October 2015, pp. 38-44

Lectures

Bischoff, R., High-sensitivity, quantitative analysis of biopharmaceuticals by LC-MS/MS, Waters Event, Nijmegen, the Netherlands, April 22, 2015

Bischoff, R., Protein biomarker discovery & development (short course), 42nd International Symposium on High Performance Liquid Phase Separations and Related Techniques (HPLC 2015), Geneva, Switzerland, June 21-25, 2015

Bischoff, R., Biomarker discovery and validation for cervical cancer and beyond …, 42nd International Symposium on High Performance Liquid Phase Separations and Related Techniques (HPLC 2015), Geneva, Switzerland, June 21-25, 2015

Horvatovich, P., Proteogenomics approach to reveal differentially expressed proteins in COPD patients, 28th Lake Louise Tandem Mass Spectrometry workshop, Lake Louise, Alberta, Canada, December 3, 2015

Horvatovich, P., Proteogenomics approach to reveal differentially expressed proteins in COPD patients, GRIAC Retrait, Groningen, the Netherlands, October 9, 2015

Horvatovich, P., Proteogenomics approach to identify new protein forms in COPD patients, 4th UTMB Brain Symposium, Galveston, Texas, USA, October 2, 2015

Horvatovich, P., In vitro transcription translation system: a versatile tool in the search for missing proteins, HUPO 2015, 13th C-HPP workshop, Vancouver, British Columbia, Canada, September 27 - October 1, 2015

Horvatovich, P., Time alignment algorithms for complex proteomics and metabolomics LC-MS(/MS) data, ISPROF 2015 conference, Caparica, Portugal, September 23, 2015

Han, J., Application of self-assembled Pd2L4 coordination cages in protein imaging and drug delivery, EU COST action (Functional metal complexes that bind to biomolecules) meeting, Belgrad, Serbia, September, 11-12, 2015

Horvatovich, P., Proteogenomics approach to reveal differentially expressed proteins in COPD patients, 5th Nordic Proteomics Symposium, the 14th Swedish Proteomics Society Symposium, Malmö, Sweden, August 23-25, 2015

Horvatovich P., Chromsome-centric human proteome project chromosome 5, 12th C-HPP Workshop, Milano, Italy, June 23, 2015


Gül, T., Optimization of reaction parameters for the electrochemical oxidation of lidocaine with a Design of Experiments approach. ElCheMS-3rd 2015, Münster, Germany, May 28-29, 2015

van de Merbel, N.C., Investigations and anomalous values with “no assigned root cause”, 9th Workshop on Recent Issues in Bioanalysis, Miami, Florida, USA, April 14-17, 2015

van de Merbel, N.C., Overcoming the hidden limitations of stable-isotope labeled (SIL) internal standards, 9th Workshop on Recent Issues in Bioanalysis, Miami, Florida, USA, April 14-17, 2015

van de Merbel, N.C., Quantitative bioanalysis by LC-MS/MS: from small to large molecules, 42nd International Symposium on High Performance Liquid Phase Separations and Related Techniques (HPLC 2015), Geneva, Switzerland, June 21-25, 2015

van de Merbel, N.C., LC-MS/MS based quantification of proteins in biological samples: current state of the art, Mini-symposium lab opening PRA Health Sciences, Assen, The Netherlands, November 5, 2015

van de Merbel, N.C., Why do LC-MS and LBA results differ? A literature evaluation, European Bioanalysis Forum, 8th Annual Open Symposium. Barcelona, Spain, November 18-20, 2015

Zhang, T., Chemical labeling of electrochemically cleaved peptides, CHAINS 2015 (Chemistry as innovating science), Veldhoven, The Netherlands. November 30 - December 2, 2015

Poster presentations

van den Brink, F.T.G., Zhang, T., Ma, L., Odijk, M., Olthuis, W., Permentier, H.P., Bischoff, R., van den Berg, A., Electrochemical protein cleavage in a microfluidic cell with integrated boron doped diamond electrodes, 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences, Gyeongju, South Korea, October 25-29, 2015

van de Merbel, N., Bronsema K, Bischoff R., Preparation and use of 18O-labeled internal standards for peptide and protein quantification by LC-MS/MS, European Bioanalysis Forum, 8th Annual Open Symposium. Barcelona, Spain, November 18-20, 2015

Ruokolainen, M., Gul, T., Permentier, H., Sikanen, T., Kostiainen, R., Kotiaho, T., Comparison of titanium dioxide photocatalysis, electrochemical reactions and electrochemically assisted fenton reaction for simulation of phase I metabolism reactions, Farmasian Päivät, Helsinki, Finland, November 13-15, 2015

Wilffert D., Bronsema K., van der Merbel N.C., Bischoff R., Targeted mass spectrometry for the analysis of biomarkers and biopharmaceuticals, 63rd Conference on Mass Spectrometry and Allied Topics (ASMS 2015), St. Louis, USA, May 31 - June 4, 2015

Yuan, T., Permentier, H.P., Bischoff, R., Nanoporous gold electrodes for the metabolic conversion of lidocaine. Poster presented at the 15th International Symposium on Electroanalytical Chemistry, Changchun, China, August 13-16, 2015

Yuan, T., Ngoc, L.L.T., van Nieuwkasteele, J., Odijk, M., van den Berg, A., Permentier, H.P., Bischoff, R., Carlen, E.T., In situ surface-enhanced Raman spectroelectrochemical analysis system with a hemin modified nanostructured gold surface. 3rd International Workshop on Electrochemistry/Mass Spectrometry, Münster, Germany, May 28-29, 2015


Zhang, T., Permentier, H.P., Bischoff, R., Specific enrichment method for electrochemically cleaved peptides. ElCheMS (3rd International Workshop onElectrochemistry/Mass Spectrometry), Münster, Germany, May 28-29, 2015

Miscellaneous

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)

Horvatovich, P., Principal Investigator of Chromosome 5 team

Awards

Yuan, T., top-twenty excellent poster presentations at the 15th International Symposium on Electroanalytical Chemistry, Changchun, China, August 13-16, 2015

van de Merbel, N.C., 2015 Bioanalysis Outstanding Contribution Award (BOSCA)

Editorial Tasks

Bischoff, R., Editor in Chief, J. Chromatogr. B (Elsevier)

Bischoff, R. & Karst, U., Guest Editors, Electrochemistry – Mass Spectrometry: From Pharmaceutical Research to Environmental Applications, Trends in Analytical Chemistry (July 2015)

Bischoff, Editorial Board Member, Advances in Precision Medicine (Whioce)

Horvatovich, P.L., Editorial Board Member, J. Proteome Res. (ACS)

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

Horvatovich, P., Secretary General of the C-HPP

Editor of the C-HPP Wiki (http://c-hpp.webhosting.rug.nl)

Horvatovich, P., Organizing and administrating the C-HPP workshops at HUPO 2015 (Vancouver, British Columbia, Canada, October 1, 2015) and EuPa (Milan, Italy, June 23, 2015)

Merbel, N.C van de, Harmonization Team Leader of the Global Bioanalysis Consortium (GBC)

Merbel, N.C van de, Topic Team Member LC-MS of Large Molecules, European Bioanalysis Forum (EBF)


Merbel, N.C van de, Topic Team Member Microsampling, European Bioanalysis Forum (EBF)


Research Grants: Funded Projects: 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 Data System Complexity (FWN) and Erik Frijlink Clinical Big Data for multifactorial diseases: from molecular profiles to precision medicine Principal investigator: Prof. Dr. Péter Horvatovich (RUG/FWN) Co-investigators: Dr. Marco Grzegorczyk and Prof. Dr. Ernst Wit (RUG/FWN, Johann Bernoulli Institute) Dr. Bart Verheij (RUG/FWN, Institute of Artificial Intelligence and Cognitive Engineering) Dr. Victor Guryev (RUG/FWN and UMCG, ERIBA, DSSC researcher, genetics bioinformatics and profile) Prof. Dr. Kathrin Thedieck (European Medical School Groningen-Oldenburg (EMS), UMCG and Medical Faculty of Oldenburg University) Dr. Corry-Anke Brandsma, Prof. Dr. Wim Timens, Prof. Dr. Dirkje Postma, Prof. Dr. Maarten van de Berge (UMCG, Pathology, GRIAC) Dr. György B. Halmos (UMCG, Department of Otorhinolaryngology, Head and Neck Surgery) Funding Period: 2016-2020 TRANSCAN-2 ERA-NET TRS-2015-00000149 Proteogenomic and targeted metabolomic analysis of ovarian cancer heterogeneity and its contribution to recurrence and therapy resistance Principal investigator: Dr. Christiane A. Opitz (Brain Cancer Metabolism Group, German Cancer Research Center, DKFZ, Heidelberg, Germany) Funding Period: 2016-2019 QNRF NPRP 8-1472-3-290 Risk Assessment of Mycotoxin Exposure through dietary intake in Qatar. Principal Investigator: Aisha Latiff (Toxicology and Multipurpose Lab, Anti Doping Lab Qatar, Doha, Qatar) Funding Period: 2016-2019


Teaching Bachelor projects 30-8-2015 / 30-10-2015 Biostatistics (bachelors) IIa March 16-April 7, 2015

IIb June 3-June 22, 2015 FATEM Feb. 11, 2015 Biotechnology (masters) 18-2-2015 COAST course, biomarker day Feb. 21, 2015 Quantitative Bioanalysis (masters) Feb. 1-19, 2015 Proteomics/Genomics (bachelors) March 16-April 02, 2015 Medical Genomics & Proteomics (bachelors) May 07-29, 2015 MALDI-TOF introduction, Hanze University of Applied Sciences

May 29, 2015

Introduction to proteomics (Faculty of Pharmacy, University of Strasbourg)

April 17, 2015

Behavioural and Cognitive Neurosciences (international masters)

Nov. 10, 2015

Medical and Pharmaceutical Drug Innovation (TopMasters)

Nov. 16-20, 2015

Mass Spectrometry (open course) 10-11-2015 / 11-11-2015 Pharmaceutical Analysis C (bachelors) 31-8-2015 / 9-10-2015 Drug Development (masters) 30-8-2015 / 30-10-2015 One-Day a Student Jan. 18, 2015 Summer School - LC-MS of Peptides and Proteins (Nijmegen)

18-2-2015

Bischoff, R., member of the ‘opleidingscommissie’ Pharmacy Bischoff, R., member of the 'toelatingscommissie' for the TopMaster MPDI Meints, J.W., member of the ‘ontwikkelteam’ Pharmacy Meints, J.W., docent beroepsvoorbereiding Klont, F., member of the 'evaluatiecommissie' Pharmacy


Outlook The integration of the Analytical Biochemistry group and the Interfaculty Mass Spectrometry Center was completed in 2015 and the joint operation is running well. I would like to thank all coworkers that made an effort and that accepted changes in their ways of working to make this happen. Keeping this successful combined operation functional is, however, a continuous effort and requires the full support of the University of Groningen and the UMCG.

2015 produced an impressive scientific output with 25 published or accepted papers, many in top journals of their respective fields. A very important development in 2015 was that my colleague Peter Horvatovich received a number of grants to support his research lines in proteogenomics, metal-based tagging for mass spectrometry and most recently from the big data initiative of the University of Groningen. I am hopeful that this will be followed up by more grants in 2016 based on the good work and the excellent output of the last couple of years.

The Biomarker Development Center (BDC) got going and produced the first

scientific output. I am looking forward to the first cross-centric validation study and our work on the qualification of sRAGE as biomarker for COPD in collaboration with the COPD Foundation. The Interfaculty Mass Spectrometry Center (IMSC) expanded its activities based on new users, collaborations and instrumentation covering some 40+ projects. A stronger demand for, and emphasis on, proteomics and metabolomics is expected in the coming years, which is an exciting prospect requiring continuous development and innovation on both the hardware and software (data analysis) side. At the moment, the IMSC is in an excellent position to contribute to and benefit from the major research lines at RuG/UMCG, such as healthy ageing. Our current expertise in many important aspects within omics research, including sample preparation, LC-MS instrumental analysis and data processing, can be exploited to strengthen molecular biological, biomedical and drug therapy-related projects and consortia. In this regard, we have recently been co-applicants for several research proposals in the field of proteogenomics which combines (personalized) genomics and proteomics for patient-specific analyses. Our experience and state-of-the-art instrumentation make the IMSC an attractive partner for research groups in the field of proteogenomics and for industrial partners in the field of biopharmaceuticals and biomarker analysis and validation. Further strengthening of our expertise and service level through new collaborations will be the major goal of the IMSC for 2016.

Thank you for your interest in this report. In case you see opportunities for

collaborations or would like to contact us for some other reason, please don't hesitate.

Documents

Analytical Biochemistry & Interfaculty MS Center · Analytical Biochemistry group on the analysis of thyroid hormones and TRAIL. He returned to Italy in the fall to finish and defend