Magdalena Gierula
Imperial College London
SerotypeProthrombinasePathologyMolecular biologyBacterial geneticsChemistryTissue factorCofactorFactor VProtein STissue factor pathway inhibitorThrombinKunitz domainCoagulationDiseaseStreptococcus pyogenesProtein CProteomicsBiochemistryMedicineBiologyMicrobiologyCell biology
Publications 14
#1Magdalena Gierula (Imperial College London)H-Index: 8
#2Josefin Ahnström (Imperial College London)H-Index: 16
Protein S is a critical regulator of coagulation that functions as a cofactor for the activated protein C (APC) and tissue factor pathway inhibitor (TFPI) pathways. It also has direct anticoagulant functions, inhibiting the intrinsic tenase and prothrombinase complexes. Through these functions, protein S regulates coagulation during both its initiation and its propagation phases. The importance of protein S in haemostatic regulation is apparent from the strong association between protein S defic...
3 CitationsSource
#1Josefin Ahnström (Imperial College London)H-Index: 16
#2Magdalena Gierula (Imperial College London)H-Index: 8
Last. David A. Lane (Imperial College London)H-Index: 11
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BACKGROUND: Activated coagulation factor X (FXa) is the serine protease component of prothrombinase, the physiological activator of prothrombin. Factor X Nottingham (A404T) and Taunton (R405G) are two naturally occurring mutations, identified in families with a bleeding phenotype. OBJECTIVE: To characterize these FX variants functionally. METHODS: The activity and inhibition of recombinant FX variants were quantified in plasma-based and pure component assays. RESULTS: The prothrombin times in FX...
1 CitationsSource
#1Magdalena Gierula (Imperial College London)H-Index: 8
#2Isabelle I. Salles-Crawley (Imperial College London)H-Index: 6
Last. Josefin Ahnström (Imperial College London)H-Index: 16
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BACKGROUND: Activated protein C (APC)-mediated inactivation of factor (F)Va is greatly enhanced by protein S. For inactivation to occur, a trimolecular complex among FVa, APC, and protein S must form on the phospholipid membrane. However, direct demonstration of complex formation has proven elusive. OBJECTIVES: To elucidate the nature of the phospholipid-dependent interactions among APC, protein S, and FVa. METHODS: We evaluated binding of active site blocked APC to phospholipid-coated magnetic ...
5 CitationsSource
#1Vahitha B. Abdul-Salam (Imperial College London)H-Index: 9
#2Giusy Russomanno (Imperial College London)H-Index: 1
Last. Beata Wojciak-StothardH-Index: 27
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Rationale: Increased expression of CLIC4 (chloride intracellular channel 4) is a feature of endothelial dysfunction in pulmonary arterial hypertension, but its role in disease pathology is not full...
13 CitationsSource
#1Robert Edwards (Imperial College London)H-Index: 133
#2Marta Pyzio (Imperial College London)H-Index: 2
Last. Shiranee Sriskandan (Imperial College London)H-Index: 45
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Invasive Streptococcus pyogenes infections are rare, with often-unexplained severity. Prompt diagnosis is desirable, as deaths can occur rapidly following onset and there is an increased, but preventable, risk to contacts. Here, proteomic analyses of clinical samples from invasive human S. pyogenes infections were undertaken to determine if novel diagnostic targets could be detected, and to augment our understanding of disease pathogenesis. Fluid samples from 17 patients with confirmed invasive ...
9 CitationsSource
#1Salvatore Santamaria (Imperial College London)H-Index: 14
#2Natalia Reglińska-Matveyev (Imperial College London)H-Index: 2
Last. Josefin Ahnström (Imperial College London)H-Index: 16
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Abstract Tissue factor pathway inhibitor (TFPI), the main inhibitor of initiation of coagulation, exerts an important anticoagulant role through the factor Xa (FXa)-dependent inhibition of tissue factor/factor VIIa (FVIIa). Protein S is a TFPI cofactor, enhancing the efficiency of FXa inhibition. TFPI can also inhibit prothrombinase assembly by directly interacting with coagulation factor V (FV) which has been activated by FXa. Since full-length TFPI associates with FV in plasma, we hypothesized...
19 CitationsSource
#1Debra Smith (Imperial College London)H-Index: 2
#2Matthew K. Siggins (Imperial College London)H-Index: 6
Last. Shiranee Sriskandan (Imperial College London)H-Index: 45
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The range of exoproteins and core exoproteome of 14 Staphylococcus aureus isolates representing major lineages associated with asymptomatic carriage and clinical disease in the UK was identified by MS proteomics using a combined database incorporating sequences derived from 39 S. aureus genomes. In all, 632 different proteins were identified and, of these, only 52 (8 %) were found in all 14 isolates whereas 144 (23 %) were found in just a single isolate. Comparison of the observed mass of each p...
4 CitationsSource
#1Mark Reglinski (Imperial College London)H-Index: 8
#2Magdalena Gierula (Imperial College London)H-Index: 8
Last. Shiranee Sriskandan (Imperial College London)H-Index: 45
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Immunity to common bacteria requires the generation of antibodies that promote opsonophagocytosis and neutralise toxins. Pooled human immunoglobulin is widely advocated as an adjunctive treatment for clinical Streptococcus pyogenes infection however, the protein targets of the reagent remain ill defined. Affinity purification of the anti-streptococcal antibodies present within pooled immunoglobulin resulted in the generation of an IgG preparation that promoted opsonophagocytic killing of S. pyog...
20 CitationsSource
#1Sofia SomajoH-Index: 3
#2Josefin AhnströmH-Index: 16
Last. Björn DahlbäckH-Index: 101
view all 6 authors...
Protein S functions as a cofactor for tissue factor pathway inhibitor (TFPI) and activated protein C (APC). The sex hormone binding globulin (SHBG)-like region of protein S, consisting of two laminin G-like domains (LG1 and LG2), contains the binding site for C4b-binding protein (C4BP) and TFPI. Furthermore, the LG-domains are essential for the TFPI-cofactor function and for expression of full APC-cofactor function. The aim of the current study was to localise functionally important interaction ...
7 CitationsSource
#1Nicola N. Lynskey (Imperial College London)H-Index: 9
#2David Goulding (Wellcome Trust Sanger Institute)H-Index: 38
Last. Shiranee Sriskandan (Imperial College London)H-Index: 45
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Group A streptococcal isolates of serotype M18 are historically associated with epidemic waves of pharyngitis and the non-suppurative immune sequela rheumatic fever. The serotype is defined by a unique, highly encapsulated phenotype, yet the molecular basis for this unusual colony morphology is unknown. Here we identify a truncation in the regulatory protein RocA, unique to and conserved within our serotype M18 GAS collection, and demonstrate that it underlies the characteristic M18 capsule phen...
49 CitationsSource