Scientific director / professor of Bio-organic synthesis
Chemical Biology is the discipline in which fundamental biological processes are studied by approaches intrinsically rooted in chemistry. The research of Herman Overkleeft is characterized by the design, synthesis and application of chemical probes in glycobiology and immunology.
Casper de Boer
Daphne van Elsland
Tom van der Wel
Annelot van Esbroeck-Weevers
Michel van de Graaff
Mark de Geus
Anouk van der Gracht
Alex van der Ham
Herman Overkleeft obtained his PhD degree in 1997 under the guidance of Professor Upendra Pandit (University of Amsterdam) on the subject of iminosugars as glycosidase inhibitors. He then did post-doctoral research with Professor Jacques van Boom (Leiden University, the Netherlands, 1997-1999) on ring-closing metathesis in the synthesis of polyhydroxylated oxacycles and azacycles, and with Professor Hidde Ploegh (Harvard Medical School, Boston, CA, USA, 1999-2001) on inhibition of proteases involved in human adaptive immunity. He returned to the Netherlands in 2001 to assume his current chair of bioorganic chemistry at Leiden University.
His current research focuses on enzyme inhibitors and activity-based probes in chemical biology and medicinal chemistry, in particular in glycobiology and immunology. Comparative activity-based protein profiling experiments are used to study cysteine proteases, proteasomes and retaining glycosidases. Competitive activity-based protein profiling has yielded selective inhibitors for five of the six catalytic activities of human constitutive proteasomes and immunoproteasomes. Activity-based probes are equipped with any of a number of fluorophores, cell surface receptor targeting moieties or with bioorthogonal tags for instalment of these by bioorthogonal chemistry.
Herman Overkleeft has a long-standing collaboration with Professor Hans Aerts (formerly University of Amsterdam, now Leiden University) on glycolipid metabolism and lysosomal storage disorders. Competitive inhibitors selective for glucosylceramidase, acid glucosylceramidase and neutral glucosylceramidase has been developed, and current focus is on the development of a dual glucosylceramide synthase/neutral glucosylceramidase inhibitor as a potential lead for clinical development towards Gaucher disease and neuropathological disorders.
Date of birth: 12 April 1969
1997 PhD, Faculty of Chemistry, University of Amsterdam, The Netherlands, 14 March 1997
Thesis title: ‘Azasugars. Synthesis and evaluation as glycosidase inhibitors’
Advisor: Prof. Dr. U.K. Pandit
1992 MSc in Chemistry, Faculty of Chemistry, University of Amsterdam, The Netherlands
Current and previous research positions
2001 – now Full Professor in Bioorganic Chemistry, Leiden Institute of Chemistry, Leiden University, The Netherlands
1999 – 2001 Post-doctoral Researcher, Department of Pathology, Harvard Medical School, Boston, MA, USA, supported by an NWO fellowship (Prof. H.L. Ploegh)
1997 – 1999 Post-doctoral Researcher, Leiden Institute of Chemistry, Leiden University, The Netherlands (Prof. J.H. van Boom)
Grants, awards, recognitions since 2010
2016 NWO Building Blocks of Life Grant with J.M.F.G. Aerts and J.J.C. Neefjes (k€ 800)
2016 Appointed Fellow of the Royal Society of Chemistry (FRSC), United Kingdom
2016 Visiting Professor at Orleans University, France
2015 Jeremy Knowles Award, Royal Society of Chemistry, United Kingdom
2015 EU ERC Proof of Concept Grant (k€ 150)
2014 NWO-CW TOP-PUNT grant with J.M.F.G. Aerts and H. Ovaa (k€ 2,000)
2013 Dutch Ministry of Education Gravitation Grant (co-applicant with J. Neefjes, P. Gros, A. Heck, C. Figdor, T. Schumacher) for the Institute of Chemical Immunology (M€ 27.6 Euro formally split over the six applicants, 10 years)
2013 EU Innovative Medicines Initiative: European Lead Factory with M. van der Stelt (k€ 829)
2013 Visiting Professor at the Technical University Berlin, Germany
2012 NWO Graduate School Grant for the Netherlands Graduate School in Chemical Biology (main applicant, k€ 800 divided equally between Leiden University, Radboud University, Groningen, University and Technical University Eindhoven)
2012 Friedrich Wilhelm Bessel Research Award, Alexander von Humboldt Foundation, Germany
2011 ZonMw Zenith grant (k€ 400)
2011 NWO-CW ChemThem Chemical Biology Grant with J.M.F.G. Aerts (k€ 500)
2011 EU ERC Advanced Grant with J.M.F.G. Aerts (k€ 3,000)
2011 ZonMw TOP Grant, main applicant F. Ossendorp (LUMC), (co-applicant k€ 237)
2011 EU-COST Action (chair)
2011 NWO-CW TA-COAST grant (k€ 164)
2011 STW grant, main applicant A.J.M. Driessen (co-applicant k€ 145)
2010 NWO-CW ECHO grant (k€ 260)
2010 BMM/CTMM/TI Pharma Grant, co-applicant; main applicant F. Ossendorp (LUMC) (k€ 336)
Contribution to teaching and supervision
- One course for BSc Molecular Science and Technology (Leiden/Delft): Biomolecular Chemistry.
- One course for MSc Chemistry at Leiden University: Chemical Biology.
Supervision of 68 PhD students and 18 postdoctoral fellows since 2001. Current employment of recent PhD students: G. de Bruin, Ascerta Pharma Oss; J. Jiang and N. Li, assistant professors at Shenzen University; S. Hoogendoorn, postdoctoral researcher at Stanford University, L.I. Willems, postdoctoral researcher at Simon Fraser University; M.T.C. Walvoort, postdoctoral researcher at MIT, now tenure track at Groningen University; P.P. Geurink, staff researcher at LUMC; M. Risseeuw, staff researcher at Ghent University; M.D. Witte, postdoctoral researcher at MIT, now tenure track at Groningen University; K.M. Bonger, postdoctoral researcher at Stanford University, now tenure track at Radboud University; M. Verdoes, postdoctoral researcher at Stanford University, now tenure track at Radboud University Medical Centre, T. Wennekes, postdoctoral researcher at Columbia University, now tenure track at Utrecht University, V.V. Kapoerchan, Program manager, Netherlands Foundation for Chemical Research, A. Knijnenburg, research staff, DSM, Sittard, B. Duivenvoorden, process engineer, Shell, K.-J. Li, Regulatory affairs specialist, ACE Pharmaceuticals, Zwolle.
Other responsibilities since 2010
- Editorial Board member of Carbohydrate Research (since 2012). Editorial Advisory Board member of the European Journal of Organic Chemistry (since 2008), ChemBioChem (since 2010) and Bioorganic Medicinal Chemistry (since 2015)
- Member of review panels for the Netherlands Organisation for Scientific Research (NWO), Deutsche Forschungsgemeinschaft (DFG), and the Finnish Academy of Sciences
- External member to PhD committees in Germany, Italy and Denmark
- Reviewer for Science, Nature Methods, Nature Chemical Biology, Nature Protocols, Nature Communications, Angewandte Chemie, Journal of the American Chemical Society, Cell Chemical Biology, Chemical Science and various organic chemistry, bioorganic chemistry, medicinal chemistry and chemical biology journals
- Member of the management board of the Institute of Chemical Immunology (2013 - present), of the Topsector Chemistry ‘Chemistry for Life’ program board (2014 - present) and of the management board of the Netherlands proteomics Centre (2008 - 2013)
- Chair of the selection committee of the KNCV ‘Gouden Medaille’ award committee (2012 - present) and of the NWO Chemical Sciences study group ‘Design and Synthesis’ (2007 - 2011)
Publication record including five recent representative publications
>450 papers and book chapters with ~11000 citations, H-index 52 (Web of Science)
Full publication record: Leiden University
- Jiang J., Kuo C.-L., Wu L., Franke C., Kallemeijn W.W., Florea B.I., Meel E. van, Marel G.A. van der, Codée J.D.C., Boot R.G., Davies G.J., Overkleeft H.S., Aerts J.M.F.G., Detection of active mammalian GH31 Alpha-glucosidases in health and disease using in-class, broad-spectrum activity-based probes. ACS Central Science. 2016, 2, 351-358.
- Bruin G. de, Xin B.T., Kraus M., Stelt M van der, Marel G.A. van der, Kisselev A.F., Driessen C., Florea B.I., Overkleeft H.S., A set of chemical tools to visualize and control human (immuno)proteasome activities. Angewandte Chemie International Edition. 2016, 55, 4199-4203.
- Bruin G. de, Xin B.-T., Florea B.I., Overkleeft H.S., Proteasome subunit selective activity-based probes report on proteasome core particle composition in a native-PAGE FRET assay. Journal of the American Chemical Society. 2016, 138, 9874-9880.
- Willems L.I., Li N., Florea B.I., Ruben M., Marel G.A. van der, Overkleeft H.S., Triple bioorthogonal ligation strategy for simultaneous labeling of multiple enzymatic activities. Angewandte Chemie International Edition. 2012, 51, 4431-4434.
- Witte M.D., Kallemeijn W.W., Aten J., Li K.-Y., Strijland A., Donker-Koopman W.E., Blijlevens B., Kramer G., Nieuwendijk A.M.C.H. van den, Florea B.I., Hooibrink B., Hollak C.E.M., Ottenhoff R., Boot R.G., Marel G.A. van der, Overkleeft H.S., Aerts J.M.F.G., Ultrasensitive in situ visualization of active glucocerebrosidase molecules. Nature Chemical Biology. 2010, 6, 907-913.
Presentations including five presentations at international conferences since 2010
57 invited presentations at universities, companies and institutes, and invited, keynote and plenary lectures at international conferences since 2010
- Comparative and competitive activity-based glycosidase profiling, American Society for Biochemistry and Molecular Biology (ASBMB), 2-6 April 2016, San Diego (USA), invited lecture
- Activity-based protein profiling in chemical biology: a focus on proteases and glycosidases, European Symposium on Biological and Organic Chemistry (ESBOC), 17-19 March 2013, Gregynog, Wales, plenary lecture
- Activity-based glycosidase profiling, 26th International Carbohydrate Symposium, Madrid, Spain, 22-27 July 2012, invited lecture
- Strategies and tools for activity-based protein profiling: a focus on proteases and glycosidases, Le giornate di chimica organica a Pavia, 3 October 2012, Pavia, Italy, plenary lecture
- Chemical biology of glucolipid metabolism in relation to lysosomal storage disorders, 2nd RSC Symposium on Chemical Biology for Drug Discovery, 20-21 March 2012, Manchester, United Kingdom, plenary lecture