Albinusdreef 2 2333ZA Leiden
Dr. Manfred Wuhrer
0031 (0)71 5265081
The Center for Proteomics and Metabolomics forms the main expertise centre and technology platform for (clinical) proteomics and metabolomics in the LUMC. The key technologies are liquid separations (liquid chromatography and capillary electrophoresis), gas chromatography, mass spectrometry and nuclear magnetic resonance. Our main field of expertise is the application of these technologies in clinical research. The Center houses over 30 state-of-the-art mass spectrometers ranging from triple-quadrupole and ion trap instruments to a range of time-of-flight and Fourier transform mass spectrometers. Most of the instruments are coupled on-line (electrospray ionization, ESI) or off-line (matrix assisted laser desorption/ionization, MALDI) to liquid separations. The MALDI instruments are used for high-throughput screening and imaging mass spectrometry, whereas the ESI mass spectrometers are used in a wide range of proteomics and metabolomics research projects for identification and quantitation of proteins, peptides and small molecules.
- Biomedical & health
- Industrial biotech
- Mass spectrometry
- Advanced liquid and gas-phase separations
- MS and NMR integration
- Proteomics, particularly clinical proteomics
- Metabolomics, in particular clinical metabolomics
- Glycomics and glycoproteomics
Expertise and Track Record
43500984129 Characterization of glycosphingolipids with an immunosuppressing function with R.M. Spaapen (Sanquin Research). 43500984043 Dehydrocholesterol reductase 24: a novel target for the treatment of nonalcoholic steatohepatitis? with Y. Wang (Leiden University). 43500984024 Targeting the HER2 receptor: finding biomarkers for optimal anti-HER2 treatment with M. Hoogstraat (NKI). 43500984009 Determining the role of lipid mediators in MSC-mediated immunomodulation with A. Wiekmeijer (Leiden University). 4350098204 In-depth mapping of the species-lipidome in the kefir community with prof.dr. B. Teusink (Free University Amsterdam). 435000033 High throughput analysis of ACPA-IgG Fab-glycosylation: clinical application and functional perspectives with dr. Y.J.P.C. Rombouts (LUMC). 435002003 Analysis of omega3 and 6 fatty acid metabolism in cigarette smoke-induced lung inflammation With Hiemstra (LUMC).
Among the unique services we offer are the combination of ion trap and FTICR mass spectrometry (MS), proteomic analysis of large (clinical) cohorts, both broadband and targeted. Among our unique infrastructure is a 15 T FTICR solariX XR and a fully automated metabolic profiler with a 600 MHz NMR, both optimized for clinical samples, and a world-wide unique GC-APCI-UHRTOF-MS for deep metabolomics analyses. Though not completely unique, our capabilities to handle and analyze very small samples with CE-UHRTOF-MS and pipelines for RPLC and HILIC, including a semi-automated sample preparation and automatic quality control for quantiative small molecule and protein glycosylation analysis are among our specialities.
We also consult on comprehensive experimental design, perform analyses and analyze the results from quantitaitve proteomics, metabolomics and mass spectrometry imaging experiments using chemo- and bioinformatics software in integrated scientific workflows. Much of this software has been at least in part been developed in our group and is now used by many research labs around the world.
Five recent projects (2013-2014) illustrating our broad range of expertise are:
1) Identification of genetic variants influencing the human plasma proteome in a population of 1,000+ individuals (http://www.ncbi.nlm.nih.gov/pubmed/23487758)
2) Identification of colorectal cancer using MALDI-TOF (http://www.ncbi.nlm.nih.gov/pubmed/25243779)
3) Detection of carbapenemases in resistant bacteria using CE-MS/MS (http://www.ncbi.nlm.nih.gov/pubmed/25155175)
4) Design of targeted proteomics experiments using MRM (http://www.ncbi.nlm.nih.gov/pubmed/24769191)
5) Global analysis of N-glycosylation in large cohorts (http://www.ncbi.nlm.nih.gov/pubmed/24527664)
We have significant experience (first publications 2008) in integrating gene and protein expression data in model systems. We have also compared genomics (NGS) and metabolomics, as well as proteomics data. Using mass spectrometry imaging, we are integrating multiple modalities (immunohistochemistry, MALDI-TOF, MALDI-FTICR etc.) using advanced bioinformatics and image analysis software largely developed in-house (http://www.ncbi.nlm.nih.gov/pubmed/25201776, http://www.ncbi.nlm.nih.gov/pubmed/24661141).
- Identification of genetic variants influencing the human plasma proteome. Johansson Å, Enroth S, Palmblad M, Deelder AM, Bergquist J, Gyllensten U. Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4673-8. doi: 10.1073/pnas.
- De novo discovery of phenotypic intra-tumor heterogeneity using imaging mass spectrometry. Balluff B, Frese CK, Maier SK, Schöne C, Kuster B, Schmitt M, Aubele M, Höfler H, Deelder AM, Heck AJ, Hogendoorn PC, Morreau J, Altelaar AF, Walch A, McDonnell LA. J Pathol. 2014 Sep 9. doi: 10.1002/path.4436
- Serum peptide signatures for pancreatic cancer based on mass spectrometry: a comparison to CA19-9 levels and routine imaging techniques. Velstra B, Vonk MA, Bonsing BA, Mertens BJ, Nicolardi S, Huijbers A, Vasen H, Deelder AM, Mesker WE, van der Burgt YE, Tollenaar RA. J Cancer Res Clin Oncol. 2014 Sep 21.
- Capillary-electrophoresis mass spectrometry for the detection of carbapenemases in (multi-)drug-resistant gram-negative bacteria. Fleurbaaij F, Heemskerk AA, Russcher A, Klychnikov OI, Deelder AM, Mayboroda OA, Kuijper EJ, van Leeuwen HC, Hensbergen PJ. Anal Chem. 2014 Sep 16;86(18):9154-61. doi: 10.1021/ac502049p
- A metabolomic profile is associated with the risk of incident coronary heart disease. Vaarhorst AA, Verhoeven A, Weller CM, Böhringer S, Göraler S, Meissner A, Deelder AM, Henneman P, Gorgels AP, van den Brandt PA, Schouten LJ, van Greevenbroek MM, Merry AH, Verschuren WM, van den Maagdenberg AM, van Dijk KW, Isaacs A, Boomsma D, Oostra BA, van Duijn CM, Jukema JW, Boer JM, Feskens E, Heijmans BT, Slagboom PE. Am Heart J. 2014 Jul;168(1):45-52.e7. doi: 10.1016/j.ahj.2014.01.019
- Structural analysis of an intact monoclonal antibody by online electrochemical reduction of disulfide bonds and Fourier transform ion cyclotron resonance mass spectrometry. Nicolardi S, Deelder AM, Palmblad M, van der Burgt YE. Anal Chem. 2014 Jun 3;86(11):5376-82. doi: 10.1021/ac500383c
- Ultrahigh resolution profiles lead to more detailed serum peptidome signatures of pancreatic cancer Simone Nicolardi, Berit Velstra, Bart J. Mertens, Bert Bonsing, Wilma E. Mesker, Rob A.E.M. Tollenaar, André M. Deelder, Yuri E.M. van der Burgt Translational Proteomics Volume 2 (March 2014) Pages 39-51. DOI: 10.1016/j.trprot.2013.12.003
- Authentication of fish products by large-scale comparison of tandem mass spectra. Wulff T, Nielsen ME, Deelder AM, Jessen F, Palmblad M. J Proteome Res. 2013 Nov 1;12(11):5253-9. doi: 10.1021/pr4006525
We have initiated and/or remain highly active and serve on the boards of several national and international technology networks, such as the Netherlands Proteomics Platform (NPP), the Netherlands Mass Spectrometry Society (NVMS), the European Cooperation in Science and Technology (COST) Action for Biomolecular Mass Spectrometry Imaging, and the US-based Association of Biomolecular Resource Facilities, ABRF, (and its Proteome Informatics Research Group, iPRG).
- We operate a broad range of sample preparation robotics (Hamilton), gas- and liquid separation systems [Agilent, Dionex (Thermo), Eksigent (SCIEX), Beckman] and mass spectrometers (SCIEX, Bruker)
We deposit much of our published data in PRIDE (ProteomeXchange) and GEO, but also make databases and spectral libraries available on our own servers when no suitable repository exists.