A5087503835- Blood Coagulation and Thrombosis Mechanisms
- Systemic Lupus Erythematosus Research
- Monoclonal and Polyclonal Antibodies Research
- Endoplasmic Reticulum Stress and Disease
- Complement system in diseases
- Platelet Disorders and Treatments
- Protease and Inhibitor Mechanisms
- Glycosylation and Glycoproteins Research
- Cell Adhesion Molecules Research
- Diabetes and associated disorders
- Signaling Pathways in Disease
- Adenosine and Purinergic Signaling
- Cancer-related gene regulation
- Venomous Animal Envenomation and Studies
- Enzyme Structure and Function
- Vitamin K Research Studies
- Advanced Fluorescence Microscopy Techniques
- Blood disorders and treatments
- DNA Repair Mechanisms
- Hemophilia Treatment and Research
- Blood properties and coagulation
- Protein Structure and Dynamics
- RNA modifications and cancer
- Peptidase Inhibition and Analysis
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
Saint Louis University
2016-2025
UCLouvain Saint-Louis Brussels
2022-2024
University of Padua
2008-2023
Saint Louis University
2020-2022
University Medical Center
2016
Azienda Ospedaliera G.Rummo
2011
Northwestern University
2011
Critically ill patients with coronavirus disease 2019 (COVID-19) have a profound hypercoagulable state and often develop coagulopathy which leads to organ failure death. Because of prolonged activated partial-thromboplastin time (aPTT), relationship anti-phospholipid antibodies (aPLs) has been proposed, but results are controversial. Functional assays for aPL (i.e., lupus anticoagulant) can be influenced by concomitant anticoagulation and/or high levels C reactive protein. The presence...
Abstract Background Considerable attention has been paid to perfluoroalkyl compounds (PFCs) because of their worldwide presence in humans, wildlife, and environment. A wide variety toxicological effects is well supported animals, including testicular toxicity male infertility. For these reasons, the understanding epidemiological associations molecular mechanisms involved endocrine-disrupting properties PFCs on human reproductive health a major concern. Objective To investigate relationship...
Increased levels of circulating complement activation products have been reported in COVID-19 patients, but only limited information is available on involvement at the tissue level. The mechanisms and pathways local remain unclear. aim this study was to investigate deposition components lungs, kidneys, liver patients with determine pathway/s activation. We performed immunofluorescence analyses autopsy specimens kidney, from 12 who died acute respiratory failure. Snap-frozen samples embedded...
Recent studies have documented the ability of prothrombin to spontaneously convert mature protease thrombin when Arg-320 becomes exposed solvent for proteolytic attack upon mutation residues in activation domain. Whether autoactivation occurs wild-type under conditions relevant physiology remains unknown. Here, we report that binding histone H4 physiological generates by autoactivation. The effect is abrogated catalytic Ser-525 and requires presence Gla Fluorescence titrations document...
Hereditary angioedema is an autosomal dominant disorder caused by defects in C1-esterase inhibitor (C1-INH), resulting poorly controlled activation of the kallikrein-kinin system and bradykinin overproduction. C1-INH a heavily glycosylated protein serine protease (SERPIN) family, yet role these glycosylation sites remains unclear. To elucidate functional impact N-glycosylation SERPIN domain C1-INH, we engineered four sets consisting 26 variants at or near N-linked sequon (NXS/T). Among...
Abstract Objectives The Certified Reference Material (CRM) ERM ® -DA477/IFCC is a new polyclonal IgG anti-beta2-glycoprotein I (anti-β2GPI) material for the harmonization of laboratory diagnosis antiphospholipid syndrome (APS). We evaluated CRM’s ability to represent heterogeneity APS patient anti-β2GPI antibodies and calibrate methods. Methods characterized CRM its reactivity against domain-1, using QUANTA Flash β2GPI-domain-1 assay, domains-4-5 β2GPI, single-domain-deleted β2GPI molecules...
The zymogen prothrombin is composed of fragment 1 containing a Gla domain and kringle-1, 2 kringle-2, protease A B chains. prothrombinase complex assembled on the surface platelets converts to thrombin by cleaving at Arg-271 Arg-320. three-dimensional architecture molecular basis its activation remain elusive. Here we report first x-ray crystal structure as Gla-domainless construct carrying an Ala replacement catalytic Ser-525. Prothrombin features conformation 80 Å long, with positioned 36°...
Protein allostery is based on the existence of multiple conformations in equilibrium linked to distinct functional properties. Although evidence allosteric transitions relatively easy identify by studies, structural detection a pre-existing between alternative remains challenging even for textbook examples proteins. Kinetic studies show that trypsin-like protease thrombin exists two where active site either collapsed (E*) or accessible substrate (E). However, demonstration exist same enzyme...
The zymogen prothrombin is proteolytically converted by factor Xa to the active protease thrombin in a reaction that accelerated >3,000-fold cofactor Va. This physiologically important effect paradigmatic of analogous cofactor-dependent reactions coagulation and complement cascades, but its structural determinants remain poorly understood. Prothrombin has three linkers connecting N-terminal Gla domain kringle-1 (Lnk1), two kringles (Lnk2), kringle-2 C-terminal (Lnk3). Recent developments...
Apolipoprotein L1 (ApoL1) is a human serum protein conferring resistance to African trypanosomes, and certain ApoL1 variants increase susceptibility some progressive kidney diseases. has been hypothesized function like pore-forming colicin reported have permeability effects on both intracellular plasma membranes. Here, gain insight into how may in vivo, we used vesicle-based ion permeability, direct membrane association, intrinsic fluorescence study the activities of purified recombinant...
Increased levels of circulating complement activation products have been reported in COVID-19 patients, but only limited information is available on involvement at tissue level. The mechanisms and pathways local remain unclear. We performed immunofluorescence analyses autopsy specimens lungs, kidney liver from nine patients who died acute respiratory failure. Snap-frozen samples embedded OCT were stained with antibodies against components products, IgG spike protein SARS-CoV-2. Lung deposits...
Prethrombin-2 is the immediate zymogen precursor of clotting enzyme thrombin, which generated upon cleavage at R15 and separation A chain catalytic B chain. The X-ray structure prethrombin-2 determined in free form 1.9 Å resolution shows 215-217 segment collapsed into active site occluding 49% volume available for substrate binding. Remarkably, some crystals harvested from same crystallization well, under identical solution conditions, diffract to 2.2 space group but produce a moves >5...