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Professor Johan Stenflo
Department of Clinical Chemistry
Lund University
Univeristy Hospital, Malmö-205 02 Malmö, Sweden
Email: johan.stenflo@klkemi.mas.lu.se
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Homepage:
| Research |
| Our research has for a long time been focused on the regulation of blood coagulation. Structure - function relationships have been intensely studied and much emphasis has been given to post-translational modifications in the vitamin K-dependent serine proteases. These studies have often been performed in collaboration with specialists on NMR spectroscopy and X-ray crystallography. Over the last couple of years we have also studied serine protese inhibitors (serpins) involved in the regulation of blood coagulation, particularly the protein C inhibitor (PCI), which is the prime inhibitor of activated protein C (APC), an important regulatory serine protease in blood coagulation. These studies have given us insight into the structural transitions that occur in serpins upon complex formation with a cognate serpin. Based on these studies we have been able to develop new assays that are potentially clinically very useful. Hence, it has, for the first time, been possible to accurately measure the normal plasma concentration of the complex between activated protein C and its cognate inhibitor, the protein C inhibitor (the APC-PCI complex). It now appears as if the APC-PCI complex concentration is the most sensitive indicator of the activation of blood coagulation in vivo. Recently, we have engaged clinical colleagues who will evaluate the potential clinical usefulness of this method. |
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| Collaborations |
Professor Bruce Furie and Professor Barbara Furie
Center for Hemostasis and Thrombosis Research,
Harvard Medical School, USA.
Professor Torbjö Drakenberg
Department of Physical Chemistry 2
Lund University, Sweden.
Professor Kristina A. Downing
Dept. of Biochemistry
University of Oxford, UK.
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| Publications |
Strandberg, K., Kjellberg, M., Erb, E.-M., Persson, U., Mosher, D., F., Villotreix, B. and Stenflo, J. (2000) Activated protein C-protein C inhibitor complex formation: Characterization of a neoepitope povides evidence for extensive insertion of the reactive center loop. Biochemistry. 39, 15713-15720.
Strandberg, K. Kjellberg, M., Knebel, R., Lilja, H. and Stenflo, J. (2001) A sensitive immunochemical assay for measuring the concentration of the activated protein C-protein C inhibitor complex in plasma. Use of a catcher antibody specific for the complexed/cleaved form of the inhibitor. Thromb. Haemost. 86, 604-610.
Huntington, J.A., Kjellberg, M. and Stenflo, J. (2003) Crystal structure of protein C inhibitor reveals the hormone binding site and the basis of heparin activation. Structure . 11, 205-215.
Brown, M.A., Stenberg, L. M., Persson, U. and Stenflo, J. (2000) Identification and purification of vitamin K-dependent proteins and peptides with monoclonal antibodies specific for g-carboxyglutamic acid. J. Biol. Chem. 275, 10795-197802.
Persson, K. E., Villoutreix, B., Thämlitz, A.-M., Knobe, K.E. and Stenflo, J. (2002) The N-terminal epidermal growth factor-like domain of factor IX. Probing its functions in the activation of factor IX and factor X with a monoclonal antibody. J. Biol. Chem. 277, 35616-35624.
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