The research in the Biomolecular Mass Spectrometry and Proteomics group focuses on the use of mass spectrometry to understand the inner workings of cells. Mass spectrometry enables the characterization of molecules that are present in cells and allows thereby the identification and characterization of proteins and other biomolecules that work together and are involved in cellular processes and in disease. The group houses an excellent array of state-of-the-art mass spectrometers, combined with extensive protein and peptide separation methods. The group has a world-renown expertise in the analysis of protein-ligand, protein-protein and protein-DNA analysis by mass spectrometry. Therefore, dedicated mass spectrometers and LC methods have been and are developed allowing the analysis of the structure and function of protein machineries.
The research of prof. dr. Albert J.R. Heck focuses on the development and implementation of innovative mass spectrometric methods for the more efficient and detailed characterization of proteins in relation to their biological function. The emphasis is on the structural characterization of proteins and post-translational modifications as well as the investigation of protein complexes and protein interactions important in e.g. protein folding, protein ligand binding, and the formation of tertiary and quaternary structures. The Heck group has a track record in proteomics and especially in the analysis of protein post-translational modifications. He has an extensive track-record in quantitative proteomics, introducing metabolic stable isotope labeling in multicellular organisms such as Drosophila and C. elegans, using SILAC for studying stem cell and B cell differentiation, and stable isotope labeling by using chemical approaches, for example to follow differential pTyr phosphorylation in differentiating stem cells. The Heck laboratory is also a pioneer in macromolecular or native mass spectrometry, which enable the analysis of intact protein assemblies by mass spectrometry. The Heck group evelops mass spectrometers dedicated for this work and applies these technologies to study the structure and dynamics of for instance transcription complexes and virus assembly.
Dr. Maarten Altelaar works on the development and implementation of novel Mass Spectrometry (MS) based proteomics technologies to study protein regulation of biological processes, with the emphasis on neurological and cancer signaling. He develops and implements novel proteomics technology to study the molecular players involved in brain development and melanoma drug resistance. For this he comprehensively target the proteome on the level of post-translational modifications, protein expression and protein-protein interactions dynamics, through novel protein (complex) enrichment and top-down MS using our recently published dual fragmentation technology.
The research of dr. Celia Berkers centres around metabolomics, an exciting upcoming field that studies the small molecule metabolite profile of the cell, using chemistry-based techniques such as LC-MS and NMR. In particular, she is interested in studying the interplay of drugs with the metabolome. Because small molecule metabolites are the ultimate downstream products of the biomolecular processes in the cell, most diseases as well as the action of drugs induce metabolic changes in cells to meet the changed demands encountered by such cells. Studying these metabolic changes can therefore aid in identifying new targets for therapeutic intervention and elucidate the mode of action of drugs. To unravel the metabolic mode of action of drugs and to study whether cells acquire drug-induced metabolic adaptations to such compounds, she uses a combination of chemical biology and LC-MS-based metabolomics methodologies, in which she combines steady-state metabolomics screens with metabolic flux studies using stable isotope labelling approaches.
Dr. Simone Lemeer focuses on the elucidation of the mechanisms of action of small molecule inhibitors in cancer cells, as well as the identification of the intrinsic resistance mechanisms that are present in those cells. Constitutive acitivity of kinases is known to be crucial for a tumor to maintain its malignant phenotype. Small molecule inhibitors are therefore attractive therapeutics as they target these kinases that are critical for tumor cell survival and proliferation. Several small molecule inhibitors have been proven successful in the clinic, but despite initial success most cancers eventually develop resistance against these drugs. Resistance to the drugs, both intrinsic and acquired is a major problem and is believed to be the major cause of failure of drug treatment. Simone uses state state of the art, high sensitive, chemical proteomics and phosphoproteomics technology to study the dynamic changes of the kinome and phosphoproteome in response to small molecule inhibitor treatment, revealing mechanisms of action and resistance pathways in cancer cells in response to drug treatment.
Dr. Bas van Breukelen is Assistant Professor of Bioinformatics for Proteomics. He is head of a small bioinformatics group in the Biomolecular Mass Spectrometry group. His goal is to write and implement algorithms that facilitate the analysis of large high throughput mass spectrometry Data and to help with the analysis of such large data sets. He is also a member of the executive committee of the Utrecht Bioinformatics Centre (UBC) which was set up to create a bioinformatics community at the university and the UMCU, to coordinate bioinformatics education and to build an infrastructure that enables Big Data analysis for example by providing HPC and storage facilities.
The group of Dr. Richard Scheltema works on unraveling protein complex topology and dynamics by mass spectrometry. Research focuses on the development of advanced LC/MS-MS platforms and analysis software to provide an in-depth, quantitative view on and spatial information between the proteins & small molecules under investigation.
Dr. Renske van Gestel is assistant professor and is mainly involved in teaching bachelor and master students at the Department of Pharmaceutical Sciences of Utrecht University.
Dr. Monique Slijper is associate professor and is mainly involved in teaching bachelor and master students at the Department of Pharmaceutical Sciences of Utrecht University. She is the programme coordinator of the master programme Drug Innovation and teaches several courses in the College of Pharmaceutical Sciences honours programme.