Klinisk kemi och koagulation

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Forskargruppsledare

Universitetslektor, adj

Jovan Antovic

Enhet: Klinisk kemi och koagulation
E-post: jovan.antovic@ki.se

Medlemmar i gruppen

Postdoc

Mikel Allend

Enhet: Klinisk kemi och koagulation
E-post: mikel.allend@ki.se

Professor, senior

Magnus Axelson

Enhet: Klinisk kemi och koagulation
E-post: Magnus.Axelson@ki.se

Professor emerita

Margareta Blombäck

Telefon: 08-517 744 37
Enhet: Klinisk kemi och koagulation
E-post: Margareta.Blomback@ki.se

Laboratorieingenjör

Benziane Boubacar

Enhet: Klinisk kemi och koagulation
E-post: Boubacar.Benziane@ki.se

Forskare

Lynn Butler

Enhet: Klinisk kemi och koagulation
E-post: lynn.butler@ki.se

Postdoc

Roza Chaireti

Enhet: Klinisk kemi och koagulation
E-post: roza.chaireti@ki.se

Docent

Tore Curstedt

Telefon: 08-517 760 82
Enhet: Klinisk kemi och koagulation
E-post: tore.curstedt@ki.se

Forskarassistent

Antonio Di Gennaro

Enhet: Klinisk kemi och koagulation
E-post: Antonio.Di.Gennaro@ki.se

Doktorand

Maria Farm

Enhet: Klinisk kemi och koagulation
E-post: maria.farm@ki.se

Anknuten

Sven Gustafsson

Enhet: Klinisk kemi och koagulation
E-post: sven.gustafsson@ki.se

Laboratorieassistent

Marie Haegerstrand-Björkman

Telefon: 08-517 761 63
Enhet: Klinisk kemi och koagulation
E-post: Marie.Haegerstrand-Bjorkman@ki.se

Senior lab manager

Anne Jämsä

Telefon: 08-517 735 65
Enhet: Klinisk kemi och koagulation
E-post: Anne.Jamsa@ki.se

Docent

Anders Kallner

Telefon: 08-517 749 43
Enhet: Klinisk kemi och koagulation
E-post: Anders.Kallner@ki.se

Anknuten

Magnus Larsson

Enhet: Klinisk kemi och koagulation
E-post: magnus.larsson@ki.se

Postdoc

Maria Magnusson

Enhet: Klinisk kemi och koagulation
E-post: Maria.Magnusson@ki.se

Anknuten

Aleksandra Mandic Havelka

Enhet: Klinisk kemi och koagulation
E-post: aleksandra.mandic.havelka@ki.se

Postdoc

Clément Naudin

Enhet: Klinisk kemi och koagulation
E-post: clement.naudin@ki.se

Postdoc

Zara Pons Vila

Enhet: Klinisk kemi och koagulation
E-post: zara.pons.vila@ki.se

Postdoc

Iva Pruner

Enhet: Klinisk kemi och koagulation
E-post: iva.pruner@ki.se

Anknuten

Åsa Sandin

Enhet: Klinisk kemi och koagulation
E-post: asa.sandin@ki.se

Anknuten

Annelie Strålfors

Telefon: 08-517 706 47
Enhet: Klinisk kemi och koagulation
E-post: annelie.stralfors@ki.se

Doktorand

Yanan Zong

Enhet: Klinisk kemi och koagulation
E-post: yanan.zong@ki.se

Associates

Postdoc

Leonardo Gottlob

E-post: leonardo.gottlob@scilifelab.se

Postdoc

Philip Busart

E-post: philip.dusart@scilifelab.se

Research focus

Combinations of proinflammatory and procoagulant reactions are the unifying principle for a variety of thrombotic disorders affecting the cardiovascular system. Thrombosis - localized clotting of the blood - may occur in the arterial or the venous circulation and has a major medical impact. Acute arterial thrombosis is the proximal cause of most cases of myocardial infarction (heart attack) and of about 80% of strokes, collectively the most common cause of death in the developed world.

Factor XII (FXII, Hageman factor) is a plasma protease that initiates the contact system. This system starts a cascade of procoagulant and proinflammatory reactions via the intrinsic pathway of coagulation, and the bradykinin-producing kallikrein-kinin system, respectively (Figure 1). The biochemistry of the contact system in vitro is well understood, however its in vivo functions are just beginning to emerge.

We have previously demonstrated that FXII is essential for thrombus formation while being dispensable for hemostatic processes that terminate blood loss. Challenging the dogma of a coagulation balance, targeting factor XII protected from cerebral ischemia without interfering with hemostasis. In contrast, excess FXII activity is associated with a life threatening inflammatory disorder, Hereditary angioedema. We recently have identified platelet polyphosphate (an inorganic polymer) and mast cell heparin as in vivo FXII activators with implications on the initiation of thrombosis and edema.

A key aspect of our work is the analysis of common principles, and cross-talk between coagulation and inflammation, to establish new biomarkers and bioassays and to identify novel therapeutic targets. 

The factor XII (FXII)-driven contact system

Figure 1: The factor XII (FXII)-driven contact system. Contact with negatively charged surfaces activates coagulation factor XII (FXII) on leukocytes, bacteria, endothelial cells, and thrombocytes and initiates pro-coagulant and pro-inflammatory protease cascades. FXII triggers fibrin formation through the factor XI (FXI)-driven intrinsic pathway of blood coagulation. Activated FXII initiates the kallikrein-kinin system that generates the pro-inflammatory peptide hormone bradykinin by plasma kallikrein (PK)-mediated cleavage of high molecular weight kininogen (HK). BK triggers intracellular signaling events that increase vascular leakage by Ena/VASP-mediated rearrangements of the endothelial cytoskeleton.

The FXII-driven contact system provides an excellent platform to test basic principles of coagulation and inflammation with new perspectives to improve diagnostics and therapies of thrombotic, inflammatory, infectious and allergic diseases. Insight into contact system functions offers the unique opportunity to develop "safe anticoagulant drugs" that interfere with thrombosis and lack the bleeding risk of all currently used anticoagulant medications. FXII inhibitors will also have beneficial anti-inflammatory potency and block edema formation with crucial clinical implications.

Current projects

  1. Crosstalk of coagulation and inflammation 
  2. Mechanisms, diagnostics and therapy of Hereditary angioedema
  3. Therapeutics, functions and diagnostics of the prothrombotic and proinflammatory FXII-driven contact system
Research area Group leader
Cholesterol metabolism Magnus Axelson
Surfactant Tore Curstedt
Contact activation system Katrin Nickel
Fibrin and Fibrin meshworks Margareta Blombäck
Quality control  Anders Kallner
Hemostasiological diagnostics Jovan Antovic
Neutrophil Extracellular Traps (NETS)  Tobias Fuchs
Endothelial System Biology     Lynn Butler  
Klinisk kemi