Lodewijk Dekker

Contact

• workRoom C13 Centre for Biomolecular Sciences
  University Park
  Nottingham
  NG7 2RD
  UK
• work0115 8466327
• lodewijk.dekker@nottingham.ac.uk

Biography

I was educated at Utrecht University, the Netherlands, where I completed my PhD in Molecular Neurobiology in 1989 in the Institute for Molecular Biology and the Rudolf Magnus Institute of Pharmacology in Utrecht. During this period I investigated the role of protein phosphorylation in synaptic function. I then undertook postdoctoral research at the Novartis Institute for Medical Research, the Imperial Cancer Research Fund and University College in London. My research was in the area of cell signaling and focused largely on the Protein Kinase C pathway. In 2001 I joined Ionix Pharmaceuticals Ltd in Cambridge as Head of Molecular Biology and then became Head of Molecular Pharmacology and Associate Director of Pharmacology. In this capacity I was project leader of an early stage drug discovery project targeting voltage gated sodium channels to develop novel analgesics. In 2005 I joined the School of Pharmacy in Nottingham as Senior Lecturer in the Division of Medicinal Chemistry and Structural Biology.My research has yielded scientific publications which to date have been cited in excess of 2200 times. My 'h-index' currently stands at 25.

Research Summary

I have an interest in molecular medicine and our laboratory operates at the interface between cell biology, biochemistry and chemistry. Our main current focus is cancer research; we explore… read more

Recent Publications

• REDDY, T.R.K., LI, C., FISCHER, P.M.F. and DEKKER, L.V., 2012. Three-Dimensional Pharmacophore Design Identifies Substituted 1,2,4-Triazole Compounds as Inhibitors of the Annexin A2-S100A10 Protein Interaction ChemMedChem. (In Press.)
• MOHAMMED, M.Z., VYJAYANTI, V.N., LAUGHTON, C.A., DEKKER, L.V., FISCHER, P.M., WILSON III, D.M., ABBOTTS, R., SHAH, S., PATEL, P.M., HICKSON, I.D. and MADHUSUDAN, S., 2011. Development and evaluation of human AP endonuclease (APE1) inhibitors in melanoma and glioma cell lines British Journal of Cancer. 104(4), 653-663
• REDDY, T.R.K., LI, C., GUO, X., MYRVANG, H.K., FISCHER, P.M. and DEKKER, L.V., 2011. Design, Synthesis, and SAR Exploration of 1-Substituted 4-Aroyl-3-hydroxy-5-phenyl-1H-pyrrol-2(5H)-one Analogs as Inhibitors of the Annexin A2–S100A10 Protein Interaction. Journal of Medicinal Chemistry. 54, 2080-2094
• LI, C., REDDY, T.R.K., FISCHER, P.M. and DEKKER, L.V., 2010. A Cy5-labelled S100A10 tracer used to identify inhibitors of the protein interaction with Annexin A2 ASSAY and Drug Development Technologies. 8(1), 85-95

• View all publications

Current Research

I have an interest in molecular medicine and our laboratory operates at the interface between cell biology, biochemistry and chemistry. Our main current focus is cancer research; we explore cancer-related protein- protein and protein-DNA interactions, either at a target validation level or hit and lead identification level.

Specific research projects include

• Annexins in cell migration. Annexin A2 is present on the cell surface of endothelial cells and breast cancer cells and has been implicated in cell migration/angiogenesis/metastasis. In collaboration with other members of the Division, we aim to explore its function using a combination of biochemical, chemical biological and cell biological approaches.
• Validation of Protein Kinase C-delta protein interactions in breast cancer metastasis. Protein Kinase C-delta has been implicated in breast cancer metastasis. We aim to explore how this kinase is regulated in breast cancer cells, focusing specifically on regulation by protein-protein interactions.
• Validation of POT1-DNA interaction as anti-cancer target. POT1 is a protein in the telomere complex. Evidence suggests that some of the anticancer activity of telomerase inhibitors is through POT1. Here we aim to explore this directly using a chemical biology approach (with Dr Charles Laughton).

Our research is supported by grants from Cancer Research UK, the Breast Cancer Campaign, the Association for International Cancer Research and the Biotechnology and Biological Sciences Research Council

Expertise

Protein chemistry, cell and molecular biology, cell signaling, protein phosphorylation, neutrophil biology, Protein Kinase C, voltage-gated sodium channels, protein interactions, fluorescent assay technology, generation of stable cell lines

Memberships of Committees and Professional Bodies

• Member of the Society for Biomolecular Sciences

Teaching

• B32A12: Group Practicals Pharmaceutical Chemistry
• B32B07: Pharmaceutical and Biological Chemistry
• B32C08: Laboratory studies in Pharmaceutical Sciences and Pharmacology
• B32C09: Concepts in Medicinal Chemistry and Drug Discovery
• B33E11: Molecular Therapeutics (convenor)
• B34H09: Research Project Study

• REDDY, T.R.K., LI, C., FISCHER, P.M.F. and DEKKER, L.V., 2012. Three-Dimensional Pharmacophore Design Identifies Substituted 1,2,4-Triazole Compounds as Inhibitors of the Annexin A2-S100A10 Protein Interaction ChemMedChem. (In Press.)
• MOHAMMED, M.Z., VYJAYANTI, V.N., LAUGHTON, C.A., DEKKER, L.V., FISCHER, P.M., WILSON III, D.M., ABBOTTS, R., SHAH, S., PATEL, P.M., HICKSON, I.D. and MADHUSUDAN, S., 2011. Development and evaluation of human AP endonuclease (APE1) inhibitors in melanoma and glioma cell lines British Journal of Cancer. 104(4), 653-663
• REDDY, T.R.K., LI, C., GUO, X., MYRVANG, H.K., FISCHER, P.M. and DEKKER, L.V., 2011. Design, Synthesis, and SAR Exploration of 1-Substituted 4-Aroyl-3-hydroxy-5-phenyl-1H-pyrrol-2(5H)-one Analogs as Inhibitors of the Annexin A2–S100A10 Protein Interaction. Journal of Medicinal Chemistry. 54, 2080-2094
• LI, C., REDDY, T.R.K., FISCHER, P.M. and DEKKER, L.V., 2010. A Cy5-labelled S100A10 tracer used to identify inhibitors of the protein interaction with Annexin A2 ASSAY and Drug Development Technologies. 8(1), 85-95
• SHAO, D., SEGAL, A.W. and DEKKER, L.V., 2010. Subcellular localisation of the p40phox component of NADPH oxidase involves International Journal of Biochemistry and Cell Biology. 42(10), 1736-43
• REDDY, T.R.K., LI, C., GUO, X., FISCHER, P.M. and DEKKER, L.V., 2010. Structure-based design, synthesis, and SAR exploration of pyrrole-2-one analogues as inhibitors of the annexin A2-S100A10 protein interaction: potential anti-angiogenesis therapeutics. Journal of Pharmacy and Pharmacology. 62(10), 1373-1374
• PACLET, M.H., DAVIDSON-MONCADA, J., LOPEZ-LLUCH, G., SHAO, D. and DEKKER, L.V., 2009. Protein Kinase C as an effector of lipid-derived second messengers. In: LARIJANI, B., WOSCHOLSKI, R. and ROSSER, C.A., eds., Lipid signalling protocols 462. Humana Press Inc, Totowa, USA. 253-263
• DEKKER, L.V., 2008. Novel approaches to drug discovery in signal transduction The Biotechnology Journal. 3(4), 428-429
• DEKKER, LODEWIJK V, DANIELS, ZOE, HICK, CAROLINE, ELSEGOOD, KATHRYN, BOWDEN, SARAH, SZESTAK, TADGE, BURLEY, J RUSSELL, SOUTHAN, ANDY, CRONK, DAVID and JAMES, IAIN F, 2005. Analysis of human Nav1.8 expressed in SH-SY5Y neuroblastoma cells. European Journal of Pharmacology. 528(1-3), 52-8
• BROWN, SEAN G, THOMAS, ALISON, DEKKER, LODEWIJK V, TINKER, ANDREW and LEANEY, JOANNE L, 2005. PKC-delta sensitizes Kir3.1/3.2 channels to changes in membrane phospholipid levels after M3 receptor activation in HEK-293 cells. American Journal of Physiology: Cell Physiology. 289(3), C543-56
• RENAULT, MARIE-ANGE, JALVY, SANDRA, POTIER, MYLèNE, BELLOC, ISABELLE, GENOT, ELISABETH, DEKKER, LODEWIJK V, DESGRANGES, CLAUDE and GADEAU, ALAIN-PIERRE, 2005. UTP induces osteopontin expression through a coordinate action of NFkappaB, activator protein-1, and upstream stimulatory factor in arterial smooth muscle cells. Journal of Biological Chemistry. 280(4), 2708-13
• DEKKER,L.V. and CRONK,D., 2005. Nav1.8 as a drug target for pain. In: COWARD,K. and BAKER,M.D., eds., Sodium channels, pain and analgesia Birkhäuser Publishing Ltd, Basel, CHE. 123-144
• PACLET, M.-H., DAVIS, C., KOTSONIS, P., GODOVAC-ZIMMERMANN, J., SEGAL, A.W. and DEKKER, L.V., 2004. <i>N</i>-Formyl peptide receptor subtypes in human neutrophils activate <small>L</small>-plastin phosphorylation through different signal transduction intermediates. Biochemical Journal. 377(2), 469-477
• BIRCH, PHILLIP J, DEKKER, LODEWIJK V, JAMES, IAIN F, SOUTHAN, ANDREW and CRONK, DAVID, 2004. Strategies to identify ion channel modulators: current and novel approaches to target neuropathic pain. Drug Discovery Today. 9(9), 410-8
• DEKKER,L.V., 2004. Introduction. In: Protein Kinase C 2nd. Kluwer Academic/Plenum Publishers, New York, USA. 1-7
• DEKKER, L.V., ed., 2004. Protein Kinase C 2nd. Kluwer Academic/Plenum Publishers, New York, USA.
• DEKKER,L.V., 2004. Protein Kinase C isotype function in neutrophils. In: Protein Kinase C 2nd. Kluwer Academic/Plenum Publishers, New York, USA. 165-190
• SHAO, D., SEGAL, A.W. and DEKKER, L.V., 2003. Lipid rafts determine efficiency of NADPH oxidase activation in neutrophils FEBS Letters. 550(1-3), 101-106
• DAVIDSON-MONCADA, J.K., LOPEZ-LLUCH, G., SEGAL, A.W. and DEKKER, L.V., 2002. Involvement of protein kinase D in Fcγ-receptor activation of the NADPH oxidase in neutrophils Biochemical Journal. 363(1), 95-103
• LÓPEZ-LLUCH, G., BIRD, M.M., CANAS, B., GODOVAC-ZIMMERMAN, J., RIDLEY, A., SEGAL, A.W. and DEKKER, L.V., 2001. Protein kinase C-δ C2-like domain is a binding site for actin and enables actin redistribution in neutrophils Biochemical Journal. 357(1), 39-47
• SCHURINGA, J J, DEKKER, L V, VELLENGA, E and KRUIJER, W, 2001. Sequential activation of Rac-1, SEK-1/MKK-4, and protein kinase Cdelta is required for interleukin-6-induced STAT3 Ser-727 phosphorylation and transactivation. Journal of Biological Chemistry. 276(29), 27709-15
• LEANEY, J L, DEKKER, L V and TINKER, A, 2001. Regulation of a G protein-gated inwardly rectifying K+ channel by a Ca(2+)-independent protein kinase C. Journal of Physiology. 534(Pt. 2), 367-79
• DEKKER, L. V. and SEGAL, A. W., 2000. Signals to Move Cells Science. ISSU 5455, 982-984
• DEKKER, L V, LEITGES, M, ALTSCHULER, G, MISTRY, N, MCDERMOTT, A, ROES, J and SEGAL, A W, 2000. Protein kinase C-beta contributes to NADPH oxidase activation in neutrophils. Biochemical Journal. 347 Pt 1, 285-9