A5057958433- Complement system in diseases
- Monoclonal and Polyclonal Antibodies Research
- Blood groups and transfusion
- Adenosine and Purinergic Signaling
- SARS-CoV-2 and COVID-19 Research
- Erythrocyte Function and Pathophysiology
- Renal Diseases and Glomerulopathies
- Protein Structure and Dynamics
- Erythropoietin and Anemia Treatment
- Blood Coagulation and Thrombosis Mechanisms
- Graphene research and applications
- Influenza Virus Research Studies
- Biochemical and Structural Characterization
- Bacterial Genetics and Biotechnology
- Hemoglobinopathies and Related Disorders
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Platelet Disorders and Treatments
- Galectins and Cancer Biology
- ZnO doping and properties
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Epilepsy research and treatment
- Quantum and electron transport phenomena
- Protein Interaction Studies and Fluorescence Analysis
- Signaling Pathways in Disease
Novo Nordisk Foundation
2024
University of Copenhagen
2024
Sorbonne Université
2022-2023
Aarhus University
2017-2023
Fontbonne University
2023
Université Paris Cité
2022
Inserm
2022
Centre de Recherche des Cordeliers
2022
Centre National de la Recherche Scientifique
2022
Freie Universität Berlin
2016
The classical pathway of complement is important for protection against pathogens and in maintaining tissue homeostasis, but excessive or aberrant activation directly linked to numerous pathologies. We describe the development vitro characterization C1qNb75, a single domain antibody (nanobody) specific C1q, pattern recognition molecule pathway. C1qNb75 binds globular head modules human C1q with sub-nanomolar affinity impedes mediated hemolysis by IgG IgM. Crystal structure analysis revealed...
Human α2-macroglobulin (A2M) is the most characterized protease inhibitor in alpha-macroglobulin (αM) superfamily, but structure of its native conformation has not been determined. Here, we combined negative stain electron microscopy (EM), small-angle X-ray scattering (SAXS), and cross-linking-mass spectrometry (XL-MS) to investigate A2M collapsed conformations that are obtained through aminolysis thiol ester by methylamine or cleavage bait region trypsin. The interpretation these data...
Hemolysis, as a result of disease or exposure to biomaterials, is characterized by excess amounts cell-free heme intravascularly and consumption the protective heme-scavenger proteins in plasma. The liberation has been linked activation inflammatory systems, including complement system, through alternative pathway activation. Here, we investigated impact on regulatory function system. Heme dose-dependently inhibited factor I-mediated degradation soluble surface-bound C3b, when incubated...
Abstract Activation of the complement system represents an important effector mechanism endogenous and therapeutic Abs. However, efficient activation is restricted to a subset Abs due requirement multivalent interactions between Ab Fc regions C1 complex. In present study, we demonstrate that Fc-independent recruitment by modular bispecific single-domain simultaneously bind C1q surface Ag can potently activate system. Using Ags from hematological solid tumors, show these are cytotoxic human...
Abstract The classical and lectin pathways of the complement system are important for elimination pathogens apoptotic cells stimulation adaptive immune system. Upon activation these pathways, component C4 is proteolytically cleaved, major product C4b deposited on activator, enabling assembly a C3 convertase downstream alternative pathway amplification. Although excessive contributes to multiple autoimmune inflammatory diseases overexpression isoform has recently been linked schizophrenia,...
The complement system is an intricate cascade of the innate immune and plays a key role in microbial defense, inflammation, organ development, tissue regeneration. There increasing interest developing regulatory inhibitory agents to treat dysfunction. In this study, we describe nanobody hC3Nb3, which specific for C-terminal C345c domain human mouse component C3/C3b/C3c potently inhibits C3 cleavage by alternative pathway. A high-resolution structure hC3Nb3-C345c complex explains how blocks...
Abstract A2ML1 is a monomeric protease inhibitor belonging to the A2M superfamily of inhibitors and complement factors. Here, we investigate protease-inhibitory mechanism human determine structures its native protease-cleaved conformations. The functional inhibitory unit monomer that depends on covalent binding (mediated by A2ML1’s thioester) achieve inhibition. In contrast tetramer which traps proteases in two internal chambers formed four subunits, disordered regions surround trapped may...
The complement system is part of the innate immune response, where it provides immediate protection from infectious agents and plays a fundamental role in homeostasis. Complement dysregulation occurs several diseases, tightly regulated proteolytic cascade turns offensive. Prominent examples are atypical hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria Alzheimer’s disease. Therapeutic intervention targeting activation may allow treatment such debilitating diseases. In...
Abstract SARS‐CoV‐2 infects cells by attachment to its receptor—the angiotensin converting enzyme 2 (ACE2). Regardless of the wealth structural data, little is known about physicochemical mechanism interactions viral spike (S) protein with ACE2 and how this has evolved during pandemic. Here, we applied experimental computational approaches characterize molecular interaction S proteins from variants concern (VOC). Data on kinetics, activation‐, equilibrium thermodynamics binding receptor...
While halogenation of graphene presents a fascinating avenue to the construction chemically and physically diverse class systems, their application in photovoltaics has been hindered by often prohibitively large optical gaps. Herein we study effects partial bromination chlorination on structure optoelectronic properties both graphane fluorographene. We find brominated chlorinated fluorographene derivatives be as stable making them likely durable even at elevated temperatures. A detailed...
Abstract Clear cell renal carcinoma (ccRCC) tumors highly express proteins of the complement system, a major innate immune defense mechanism. Exploring spatial transcriptome and making an atlas staining patterns by ultra-high multiplex imaging ccRCC tumor sections, we revealed presence regions with co-regulated overexpression components, including C3 Factor H (FH). The strong for these correlated poor prognosis in patient cohort. These interacted physically lysosomes cells situ, as evidenced...
Abstract SARS-CoV-2 infects cells by attachment to its receptor – the angiotensin converting enzyme 2 (ACE2). Regardless of wealth structural data, little is known about physicochemical mechanism interactions viral spike (S) protein with ACE2 and how this has evolved during pandemic. Here, we applied experimental computational approaches characterize molecular interaction S proteins from variants concern (VOC). Data on kinetics, activation- equilibrium thermodynamics binding domain (RBD) VOC...