A5102772579- Monoclonal and Polyclonal Antibodies Research
- Nanoparticles: synthesis and applications
- Glycosylation and Glycoproteins Research
- Alzheimer's disease research and treatments
- Carcinogens and Genotoxicity Assessment
- Bacteriophages and microbial interactions
- Air Quality and Health Impacts
- Microplastics and Plastic Pollution
- Transgenic Plants and Applications
- Radiopharmaceutical Chemistry and Applications
- Protein purification and stability
- Protein Structure and Dynamics
- Toxic Organic Pollutants Impact
- Molecular Communication and Nanonetworks
- Advanced Cellulose Research Studies
- Electrospun Nanofibers in Biomedical Applications
- Click Chemistry and Applications
- HER2/EGFR in Cancer Research
- Effects and risks of endocrine disrupting chemicals
- Inhalation and Respiratory Drug Delivery
- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- Heavy Metal Exposure and Toxicity
- Nanotechnology research and applications
- Aluminum toxicity and tolerance in plants and animals
KTH Royal Institute of Technology
2012-2024
Uppsala University
2023
AlbaNova
2012-2020
Finnish Institute of Occupational Health
2009-2020
Finnish Safety and Chemicals Agency
2020
Some multi-walled carbon nanotubes (MWCNTs) induce mesothelioma in rodents, straight MWCNTs showing a more pronounced effect than tangled MWCNTs. As primary and secondary genotoxicity may play role MWCNT carcinogenesis, we used battery of assays for DNA damage micronuclei to compare the (MWCNT-S) (MWCNT-T) vitro (primary genotoxicity) vivo or genotoxicity). C57Bl/6 mice showed dose-dependent increase strand breaks, as measured by comet assay, lung cells 24 h after single pharyngeal...
The HER3 receptor is implicated in the progression of various cancers as well resistance to several currently used drugs, and hence a potential target for development new therapies. We have previously generated Affibody molecules that inhibit heregulin-induced signaling pathways. aim this study was improve affinity binders hopefully increase inhibition efficacy enable high receptor-mediated uptake tumors. explored novel strategy maturation based on alanine scanning followed by design library...
Nanofibrillated cellulose (NFC) is a renewable nanomaterial that has beneficial uses in various applications such as packaging materials and paper. Like carbon nanotubes (CNT), NFCs have high aspect ratio favorable mechanical properties. The also rises concern whether NFC could pose health risk induce pathologies, similar to those triggered by multi-walled CNT. In this study, we explored the immunomodulatory properties of four vitro vivo, compared results with data on bulk-sized fibrils...
Abstract The amyloid hypothesis suggests that accumulation of β (Aβ) peptides in the brain is involved development Alzheimer's disease. We previously generated a small dimeric affinity protein inhibited Aβ aggregation by sequestering prone parts peptide. originally based on Affibody scaffold, but evolved to distinct interaction mechanism involving complex structural rearrangement both peptide and proteins upon binding. aim this study was decrease size significantly improve its for increase...
In this study, two sets of methyl-coated non-porous and mesoporous amorphous silica materials target sizes (100 300 nm; 10–844 m2/g) were used to investigate the potential role specific surface area (SSA) porosity on oral toxicity in mice. Female Swiss mice administered by gavage for 5 consecutive days. Two dose levels 1000 mg/kg b.w.) tested all four materials. All dispersions characterized transmission electron microscopy (TEM) Nanoparticle tracking analysis (NTA). Batch porous rather...
Materials can be modified for improved functionality. Our aim was to test whether pulmonary toxicity of silica nanomaterials is increased by the introduction of: a) porosity; and b) surface doping with CuO; c) these modifications act synergistically. Mice were exposed intratracheal instillation some doses also oropharyngeal aspiration to: 1) solid 100 nm; 2) porous 3) nm CuO doping; 4) 300 5) 6) 7) 8) nanoparticles 9.8 or 9) carbon black Printex 90 as benchmark. Based on a pilot study, dose...
Different strategies for treatment and prevention of Alzheimer's disease (AD) are currently under investigation, including passive immunization with anti-amyloid β (anti-Aβ) monoclonal antibodies (mAbs). Here, we investigate the therapeutic potential a novel type Aβ-targeting agent based on an affibody molecule fundamentally different properties to mAbs. We generated candidate, denoted ZSYM73-albumin-binding domain (ABD; 16.8 kDa), by genetic linkage dimeric ZSYM73 sequestering monomeric...
Micronuclei (MN), used as a biomarker of effect in exposure to genotoxic carcinogens, derive from chromosomes and chromosomal fragments lagging behind anaphase. The two types MN are usually distinguished each other by centromeric fluorescence situ hybridization (FISH), centromere-positive (C+) representing entire centromere-negative (C−) fragments. incorporation various chromatids is still poorly understood. We directly labelled pancentromeric pantelomeric DNA probes examine the contents...
Affibody molecules are a class of small (ca.7 kDa) robust scaffold proteins with high potential as tracers for radionuclide molecular imaging in vivo. Incorporation cysteine-containing peptide-based chelator at the C terminus provides an opportunity stable labelling (99m)Tc. The use GGGC has provided lowest renal radioactivity retention previously investigated chelators. Previously, it also been demonstrated that replacement His(6)-tag negatively charged...
Abstract Affibodies targeting amyloid-beta (Aβ) could potentially be used as therapeutic and diagnostic agents in Alzheimer’s disease (AD). display suitable characteristics for imaging applications such high stability a short biological half-life. The aim of this study was to explore brain delivery retention Aβ protofibril-targeted affibodies wild-type (WT) AD transgenic mice evaluate their potential agents. Two affibodies, Z5 Z1, were fused with the blood–brain barrier (BBB) shuttle...
Abstract Protofibrils of the 42 amino acids long amyloid-β peptide are transient pre-fibrillar intermediates in process aggregation into amyloid plaques and thought to play a critical role pathology Alzheimer’s disease. Hence, there is need for research reagents potential diagnostic detection imaging such aggregates. Here we describe an vitro selection Affibody molecules that bind protofibrils Aβ cc, which stable engineered mimic wild type protofibrils. Several binders were identified cc...
The use of biotherapeutics for the treatment diseases central nervous system (CNS) is typically impeded by insufficient transport across blood–brain barrier. Here, we investigate a strategy to potentially increase uptake into CNS an affibody molecule (ZSYM73) via binding transferrin receptor (TfR). ZSYM73 binds monomeric amyloid beta, peptide involved in Alzheimer’s disease pathogenesis, with subnanomolar affinity. We generated tri-specific fusion protein genetically linking single-chain...
Abstract The objective of our study was to develop a micronucleus (MN) assay for detecting genotoxic damage after inhalation exposure in mouse alveolar Type II and Clara cells, potential target cells lung carcinogens. Ten male C57BL/6J mice were exposed ethylene oxide (630 mg/m 3 ) 4 hr via inhalation; 10 unexposed serving as controls. 72 the exposure, isolated using two different methods. Method 1 included 15‐min trypsin lavage 2‐hr incubation cell suspension. 2 involved 30‐min lavage,...
We have previously generated an affibody molecule for the disease-associated amyloid beta (Aβ) peptide, which has been shown to inhibit formation of various Aβ aggregates and revert neurotoxicity in a fruit fly model Alzheimer's disease. In this study, we investigated new bacterial display system combinatorial protein engineering Aβ-binder as head-to-tail dimeric construct future optimization efforts, e.g. affinity maturation. Using platform, have: (i) demonstrated functional expression...
Affibody molecules are small (6-kDa) affinity proteins folded in a three-helical bundle and generated by directed evolution for specific binding to various target molecules. The most advanced affibody currently tested the clinic, data from more than 300 subjects show excellent activity safety profiles. generation of against particular starts with an library, which can then be used panning using multiple methods selection systems. This protocol describes molecular cloning DNA-encoded...