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Dr. Jeroen Kool is an analytical chemist with research interests in high resolution screening of biologically active compounds. During his PhD study (2001-2005) at VU University, he focused on the integration of chemical - e.g. mass spectrometry (MS) - with biochemical detection after separation methodologies. Moreover, he worked on post-column coupling of enzyme and receptor assays that are relevant for toxicological and pharmacological studies to study drug-drug interactions, reactive intermediates and pharmacologically active metabolites. Following his doctorate, Kool joined Kiadis Pharma where he was responsible for target evaluation, hit screening and identification and lead optimization processes. His work mainly involved high resolution screening technologies in combination with MS identification, and the mammalian cellular screening portfolio.

 

Dr. Kool continued his academic career as a postdoctoral fellow in the Biomolecular Mass Spectrometry group at Utrecht University. There he worked on proteomics (biomarker discovery) focusing on complex regional pain syndrome. In 2007, Dr. Kool was appointed assistant professor at the Division of Biomolecular Analysis at VU University, where he is responsible for the research line Bioactivity Screening Methodologies. His research achievements allow full compatibility of analytical separations with biological assays (including cellular) and parallel MS detection for investigation of bioactive mixtures (metabolic mixtures, venoms, natural extracts) using miniaturized setups and nanospotting technologies.

 

In Dr. Kool’s focus on identification and characterization of bioactive compounds in biological mixtures, hyphenated analytics combining mass spectrometry and chromatography with novel bioassay techniques are integrated in one platform. We hyphenate both LC and GC separations to bioassays for identification of biologically active toxicants in food and the environment. In case of GC fractionations, we developed and patented an automated system for high resolution fractionation of complete GC chromatograms with parallel chemical detection, such as FID and MS. With this new technology one of our visions is to develop methods for screening organisms known to produce volatile antibiotics. Identification of these antibiotics might result in developing them further as inhaler administration type of drug candidates for pneumonia infections by bacteria such as tuberculosis and legionella.

 

Also, we developed analytical methodologies for bioactivity profiling of metabolic mixtures from drugs and lead compounds targeting GPCRs, nuclear receptors, protein kinases and ion channels. Currently, we are working on post-column microfluidics and nanofractionation analytics for analysis of bioactive mixtures only available in low amounts. Nice examples are insect and animal venoms that contain many different, highly potent, and sometimes very selective protein ligands for a large variety of medicinal targets. These analytics have additional implementation of proteomics approaches for identification of venom peptides for venom based drug discovery programs towards novel biopharmaceutical candidates.

 

The latest research Dr. Kool has initiated is directed at microfluidic spotting techniques (using nanospotters) for combining nanoLC with post-column array spotted bioassays. Readout of biological responses will occur with our new confocal microscope imaging scanner currently being developed together with our university’s precision mechanics and instrumental development groups. The microfluidics spotter & confocal imaging scanner technology will be directed at the discovery and identification of new antibiotic drug candidates in complex natural extracts from tropical plants and from coral reef anemones, sponges, and other invertebrates.

Ancillary activities

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Last update Ancillary Activities: Amsterdam (2018-02-23)

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Research Output 2000 2017

  • 71 Article
  • 4 PhD Thesis - Research VU, graduation VU

Improved androgen specificity of AR-EcoScreen by CRISPR based glucocorticoid receptor knockout

Zwart, N., Andringa, D., de Leeuw, W. J., Kojima, H., Iida, M., Houtman, C. J., de Boer, J., Kool, J., Lamoree, M. H. & Hamers, T. 1 Dec 2017 In : Toxicology in Vitro. 45, p. 1-9 9 p.

Research output: Scientific - peer-reviewArticle

At-line cellular screening methodology for identification of bioactives in mixtures targeting the alpha7-n AChR.

Ötvös, R. A., Mladic, M., Arias-Alpizar, G., Niessen, W. M. A., Somsen, G. W., Smit, A. B. & Kool, J. 2016 In : Journal of Biomolecular Screening. 21, p. 459-467

Research output: Scientific - peer-reviewArticle

At-line nanofractionation with parallel mass spectrometry and bioactivity assessment for the rapid screening of thrombin and factor Xa inhibitors in snake vemoms.

Mladic, M., Zietek, B. M., Krishnamoorthy Iyer, J., Hermarij, P., Niessen, W. M. A., Somsen, G. W., Kini, R. M. & Kool, J. 2016 In : Toxicon. 110, p. 79-89

Research output: Scientific - peer-reviewArticle

Gas chromatography fractionation platform featuring parallel flame ionization detection and continuous high-resolution analyte collection in 384-well plates.

Jonker, W., Clarijs, B., de Witte, S. L., van Velzen, M. J. M., de Koning, S., Schaap, J., Somsen, G. W. & Kool, J. 2016 In : Journal of Chromatography A. 1462, p. 100-106

Research output: Scientific - peer-reviewArticle