A5102721021- Proteoglycans and glycosaminoglycans research
- Glycosylation and Glycoproteins Research
- Malaria Research and Control
- Radiopharmaceutical Chemistry and Applications
- RNA Interference and Gene Delivery
- Monoclonal and Polyclonal Antibodies Research
- Photosynthetic Processes and Mechanisms
- Electrochemical sensors and biosensors
- Immunotherapy and Immune Responses
- Microbial Fuel Cells and Bioremediation
- Cancer Cells and Metastasis
- Photoreceptor and optogenetics research
- Bladder and Urothelial Cancer Treatments
- Electrochemical Analysis and Applications
- SARS-CoV-2 and COVID-19 Research
- HIV Research and Treatment
- Cell Adhesion Molecules Research
- Neonatal Health and Biochemistry
- Enzyme Structure and Function
- Cancer Genomics and Diagnostics
- Glioma Diagnosis and Treatment
- Viral Infectious Diseases and Gene Expression in Insects
- Mosquito-borne diseases and control
- ATP Synthase and ATPases Research
- SARS-CoV-2 detection and testing
University of Copenhagen
2016-2025
Uppsala University
2023-2024
Copenhagen University Hospital
2015-2023
Rigshospitalet
2022
Lund University
1995-2012
Innovation Center Iceland
1995
Virus-like particles (VLPs) represent a significant advance in the development of subunit vaccines, combining high safety and efficacy. Their particulate nature dense repetitive organization makes them ideal scaffolds for display vaccine antigens. Traditional approaches VLP-based antigen require labor-intensive trial-and-error optimization, often fail to generate display. Here we utilize split-intein (SpyTag/SpyCatcher) conjugation system stable isopeptide bound antigen-VLP complexes by...
Abstract The rapid development of a SARS-CoV-2 vaccine is global priority. Here, we develop two capsid-like particle (CLP)-based vaccines displaying the receptor-binding domain (RBD) spike protein. RBD antigens are displayed on AP205 CLPs through split-protein Tag/Catcher, ensuring unidirectional and high-density display RBD. Both soluble recombinant bind ACE2 receptor with nanomolar affinity. Mice vaccinated or CLP-displayed RBD, formulated in Squalene-Water-Emulsion. RBD-CLP induce higher...
Abstract Isolation of metastatic circulating tumor cells (CTCs) from cancer patients is high value for disease monitoring and molecular characterization. Despite the development many new CTC isolation platforms in last decade, their detection has remained a challenge due to lack specific sensitive markers. In this feasibility study, we present method based on binding malaria rVAR2 protein oncofetal chondroitin sulfate (ofCS). We show that efficiently captures CTCs hepatic, lung, pancreatic,...
Capsid virus-like particles (cVLP) have proven safe and immunogenic can be a versatile platform to counter pandemics. We aimed clinically test modular cVLP COVID-19 vaccine in individuals who were naive SARS-CoV-2.In this phase 1, single-centre, dose-escalation, adjuvant-selection, open-label clinical trial, we recruited participants at the Radboud University Medical Center Nijmegen, Netherlands, sequentially assigned them seven groups. Eligible healthy, aged 18-55 years, tested negative for...
Diffuse gliomas are the most common primary malignant brain tumor. Although extracranial metastases rarely observed, recent studies have shown presence of circulating tumor cells (CTCs) in blood glioma patients, confirming that a subset capable entering circulation. The isolation and characterization CTCs could provide non-invasive method for repeated analysis mutational phenotypic state during course disease. However, efficient detection has proven to be challenging due lack consistently...
The present study explores genetic engineering of the respiratory chain and application two different flexible osmium redox polymers to achieve efficient electric communication between gram-positive organism Bacillus subtilis an electrode. Poly(1-vinylimidazole)12-[Os-(4,4′-dimethyl-2,2′-bipyridyl)2Cl2]+/2+ (osmium polymer I) poly(vinylpyridine)-[Os-(N,N′-methylated-2,2′-biimidazole)3]2+/3+ II) were investigated for electrical "wiring" viable bacterial cells electrodes. Using a B. strain...
Placental malaria can have severe consequences for both mother and child effective vaccines are lacking. Parasite-infected red blood cells sequester in the placenta through interaction between parasite-expressed protein VAR2CSA glycosaminoglycan chondroitin sulfate A (CS) abundantly present intervillous space. Here, we report cryo-EM structures of ectodomain at up to 3.1 Å resolution revealing an overall V-shaped architecture a complex domain organization. Notably, surface displays single...
Malaria infected erythrocytes utilize the parasite protein VAR2CSA to bind a unique presentation of chondroitin sulfate (CS) for their placenta specific tropism. Interestingly, many cancers express similar form CS, thereby termed oncofetal CS (ofCS). The distinctive tropism malaria and identification therefore, represent potentially potent tools cancer targeting. Here we describe an intriguing drug delivery platform that effectively mimics specificity ofCS. We used lipid catcher-tag...
Pretargeted radioimmunoimaging has been shown to enhance tumor-to-background ratios by up 125-fold at early time points, leading more efficient and less toxic radionuclide therapies, particularly with shorter half-lives such as astatine-211 (211At). The tetrazine ligation is the most utilized bioorthogonal reaction in these strategies, making tetrazines ideal for 211At labeling controlling biodistribution. We developed a 211At-labeled pretargeting agent alpha-radionuclide therapy, achieving...
Pretargeted imaging harnessing tetrazine ligation has gained increased interest over recent years. Targeting vectors with slow pharmacokinetics may be visualized using short-lived radionuclides, such as fluorine-18 (18F) for positron emission tomography (PET), and result in improved target-to-background ratios compared to conventionally radiolabeled slowly accumulating vectors. We recently developed different radiochemical protocols enabling the direct radiofluorination of various scaffolds,...
The crystal structure of the flavodoxin-like protein WrbA with oxidized FMN bound reveals a close relationship to mammalian NAD(P)H:quinone oxidoreductase, Nqo1. Structural comparison WrbA, flavodoxin, and Nqo1 indicates how twisted open-sheet fold flavodoxins is elaborated form multimers that extend catalytic function from one-electron transfer between partners using two-electron reduction xenobiotics FAD. suggests novel physiological role for
Abstract Lineage plasticity of prostate cancer is associated with resistance to androgen receptor (AR) pathway inhibition (ARPI) and supported by a reactive tumor microenvironment. Here we show that changes in chondroitin sulfate (CS), major glycosaminoglycan component the cell glycocalyx extracellular matrix, AR-regulated promotes adaptive progression castration-resistant (CRPC) after ARPI. AR directly represses transcription 4- O -sulfotransferase gene CHST11 under basal conditions,...
Background: The development of bispecific antibodies that can traverse the blood–brain barrier has paved way for brain-directed immunotherapy and when radiolabelled, immunoPET imaging. objective this study was to investigate how indium-111 (111In) radiolabelling with compatible chelators affects brain delivery peripheral biodistribution antibody RmAb158-scFv8D3, which binds amyloid-beta (Aβ) transferrin receptor (TfR), in Aβ pathology-expressing tg-ArcSwe mice aged-matched wild-type control...
Chondroitin sulfate (CS) is the placental receptor for VAR2CSA malaria protein, expressed at surface of infected erythrocytes during Plasmodium falciparum infection. Infected cells adhere to syncytiotrophoblasts or get trapped within intervillous space by binding a determinant in 4-O-sulfated CS chains. However, exact structure these glycan sequences remains unclear. VAR2CSA-reactive also tumor cells, making it an attractive target cancer diagnosis and therapeutics. The identities...
The malaria protein VAR2CSA binds oncofetal chondroitin sulfate (ofCS), a unique sulfate, expressed on almost all mammalian cancer cells. Previously, we produced bispecific construct targeting ofCS and human T cells based anti-CD3 (V-aCD3Hu). V-aCD3Hu showed efficacy against xenografted tumors in immunocompromised mice injected with immune at the tumor site. However, complex effects potentially exerted by system as result of treatment cannot occur without an system. Here investigate V-aCD3Mu...
The E. coli protein WrbA is an FMN-dependent NAD(P)H:quinone oxidoreductase that has been implicated in oxidative defense. Three subunits of the tetrameric enzyme contribute to each four identical, cavernous active sites appear accommodate NAD(P)H or various quinones, but not simultaneously, suggesting obligate tetramer with a ping-pong mechanism which NAD departs before oxidized quinone binds. present work was undertaken evaluate these suggestions and characterize kinetic behavior WrbA....
Placental malaria infection is mediated by the binding of malarial VAR2CSA protein to placental glycosaminoglycan, chondroitin sulfate. Recombinant subfragments (rVAR2) have also been shown bind specifically and with high affinity cancer cells tissues, suggesting presence a shared type oncofetal sulfate (ofCS) in placenta tumors. However, exact structure ofCS what determines selective tropism remains poorly understood. In this study, was purified chromatography using rVAR2 subjected detailed...
Malaria during pregnancy is a major global health problem caused by infection with Plasmodium falciparum parasites. Severe effects arise from the accumulation of infected erythrocytes in placenta. Here, late blood-stage parasites adhere to placental chondroitin sulphate A (CS) via VAR2CSA-type P. erythrocyte membrane protein 1 (PfEMP1) adhesion proteins. Immunity malaria acquired through exposure and mediated antibodies VAR2CSA. Through evolution, VAR2CSA proteins have diversified sequence...
Abstract Proteoglycans in bladder tumors are modified with a distinct oncofetal chondroitin sulfate (ofCS) glycosaminoglycan that is normally restricted to placental trophoblast cells. This ofCS-modification can be detected by the malarial VAR2CSA protein, which malaria pathogenesis mediates adherence of parasite-infected erythrocytes within placenta. In cancer, proteoglycans constantly shed into urine, and therefore have potential used for detection disease. this study we investigated...