A5038326552- Neurobiology and Insect Physiology Research
- Heat shock proteins research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Retinoids in leukemia and cellular processes
- Epigenetics and DNA Methylation
- Antioxidant Activity and Oxidative Stress
- RNA modifications and cancer
- MicroRNA in disease regulation
- Enzyme Structure and Function
- Neonatal Respiratory Health Research
- Histone Deacetylase Inhibitors Research
- CRISPR and Genetic Engineering
- Congenital heart defects research
- Photodynamic Therapy Research Studies
- Proteoglycans and glycosaminoglycans research
- Sarcoma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Cancer-related molecular mechanisms research
- Fibroblast Growth Factor Research
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Down syndrome and intellectual disability research
- Estrogen and related hormone effects
- Genetics and Neurodevelopmental Disorders
- Pluripotent Stem Cells Research
Oslo University Hospital
2014-2023
Cancer Registry of Norway
2018
University of Geneva
2006-2017
University Hospital of Geneva
2011-2014
Geneva College
2014
Wrocław University of Science and Technology
2001-2008
Institute of Organic Chemistry
2001-2005
The molecular chaperone Hsp90 has been found to be essential for viability in all tested eukaryotes, from the budding yeast Drosophila. In mammals, two genes encode highly similar and functionally largely redundant isoforms Hsp90α Hsp90β. Although they are co-expressed most if not cells, their relative levels vary between tissues during development. Since mouse embryos lacking Hsp90β die at implantation, despite fact that inhibitors being as anti-cancer agents relatively well tolerated,...
// Anastassia Serguienko 1,2 , Iwona Grad Anna B. Wennerstrøm Leonardo A. Meza-Zepeda 1,3 Bernd Thiede 4,5 Eva W. Stratford Ola Myklebost 1,2,5 and Else Munthe 1 Department of Tumor Biology, Institute Cancer Research, The Norwegian Radium Hospital, Oslo University Oslo, Norway 2 Stem Cell Innovation Centre, 3 Genomics Core Facility, 4 Biotechnology Centre 5 Biosciences, Correspondence: Munthe, email: Keywords : ROS, OXPHOS, glycolysis, mitochondria, HMOX1 Received September 17, 2014 Accepted...
The functions of molecular chaperones have been extensively investigated biochemically in vitro and genetically bacteria yeast.We embarked on a functional genomic analysis the Hsp90 chaperone machine mouse by disrupting p23 gene using trap approach.p23 is an cochaperone that thought to stabilize Hsp90-substrate complexes and, independently, act as cytosolic prostaglandin E2 synthase.Gene deletions budding fission yeasts knock-down experiments with worm not revealed any clear vivo...
The molecular chaperone Hsp90 assists a subset of cellular proteins and is essential in eukaryotes. A cohort cochaperones contributes to regulates the multicomponent machine. Unlike biochemical activities cochaperone p23, its vivo functions structure-function relationship remain poorly understood, even genetically tractable model organism Saccharomyces cerevisiae. SBA1 gene that encodes p23 ortholog this species not an gene. We found absence p23/Sba1p, yeast mammalian cells are...
Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible fibrotic lung disease, resulting in respiratory insufficiency reduced survival. Pulmonary result of repeated alveolar epithelial microinjuries, followed by abnormal regeneration repair processes the lung. Recently, stem cells their secretome have been investigated as novel therapeutic approach fibrosis. We evaluated potential induced pluripotent (iPSC) conditioned media (iPSC-cm) to regenerate epithelium vitro improve...
Abstract Osteosarcoma (OS) remains a dismal malignancy in children and young adults, with poor outcome for metastatic recurrent disease. Immunotherapies OS are not as promising some other cancer types due to intra-tumor heterogeneity considerable off-target expression of the potentially targetable proteins. Here we show that chimeric antigen receptor (CAR) T cells could successfully target an isoform alkaline phosphatase, ALPL-1, which is highly specifically expressed primary OS. The...
Abstract Background Osteosarcoma is the most common primary malignant tumour of bone occurring in children and young adolescents characterised by complex genetic epigenetic changes. The miRNA miR-486-5p has been shown to be downregulated osteosarcoma cancer general. Results To investigate if mir-486 locus epigenetically regulated, we integrated DNA methylation expression data using cohorts cell lines patient samples. A CpG island promoter ANK1 host gene was highly methylated as determined...
Sarcomas are rare cancers with limited treatment options. Patients generally treated by chemotherapy and/or radiotherapy in combination surgery, and would benefit from new personalized approaches. In this study we demonstrate the potential of combining personal genomic characterization patient tumors to identify targetable mutations vitro testing specific drugs patient-derived cell lines. We have analyzed three metastases a high-grade metastatic dedifferentiated liposarcoma (DDLPS) exome...
Reprogramming somatic cells into a pluripotent state brings patient-tailored, ethical controversy-free cellular therapy closer to reality.However, stem and cancer share many common characteristics; therefore, it is crucial be able discriminate between them.We generated two induced cell (iPSC) lines, with NANOG pre-transduction followed by OCT3/4, SOX2, LIN28 overexpression.One of the CHiPS W, showed normal characteristics, while other, A, though expressing pluripotency markers, failed...
Background: FGFR inhibition has been proposed as treatment for dedifferentiated liposarcoma (DDLPS) with amplified FRS2, but we previously only demonstrated transient cytostatic effects when treating FRS2-amplified DDLPS cells NVP-BGJ398. Methods: Effects of the more potent inhibitor LY2874455 were investigated in three cell lines by measuring on growth and apoptosis vitro also testing efficacy vivo. Genome, transcriptome protein analyses performed to characterize signaling components...
The steroid hormone, 20‐hydroxyecdysone (20E), directs Drosophila metamorphosis via a heterodimeric receptor formed by two members of the nuclear hormone receptors superfamily, product EcR (EcR) and ultraspiracle (Usp) genes. Our previous study [Niedziela‐Majka, A., Kochman, M., Ożyhar, A. (2000) Eur. J. Biochem. 267, 507–519] on Usp DNA‐binding domains (EcRDBD UspDBD, respectively) suggested that UspDBD may act as specific anchor preferentially binds 5′ half‐site pseudo‐palindromic response...
Ecdysteroids coordinate molting and metamorphosis in insects via a heterodimer of two nuclear receptors, the ecdysone receptor (EcR) ultraspiracle (Usp) protein. Here we show how DNA-recognition alpha-helix T box region EcR DNA-binding domain (EcRDBD) contribute to specific interaction with natural response element stabilization EcRDBD molecule. The data indicate remarkable mutational tolerance respect function EcRDBD. This is particularly manifested heterocomplexes formed between mutants...
Down syndrome (DS, trisomy 21), is the most common viable chromosomal disorder, with an incidence of 1 in 800 live births. Its phenotypic characteristics include intellectual impairment and several other developmental abnormalities, for majority which pathogenetic mechanisms remain unknown. In this "Data Brief" paper, we sum up whole genome analysis by mRNA sequencing normal DS induced pluripotent stem cells that was recently published Hibaoui et al. EMBO molecular medicine.
p23 is a small acidic protein with intrinsic molecular chaperone activity. It best known as co-chaperone of the major cytosolic Hsp90. binds N-terminus Hsp90 and stabilizes ATP-bound N-terminally closed dimer. in this configuration that many clients are most stably bound. Considering important role cycle, it came surprise not absolutely essential for viability budding yeast or mouse development. Mice without develop quite normally until birth then all die perinatally because immature lungs....
Bone marrow mesenchymal stem cells (BM-MSCs) mediate skeletal remodeling by differentiating into osteoblasts. However, this is impaired with aging as well following long-term glucocorticoid treatment, resulting in osteoporosis. In study, we report a novel factor of osteoblast differentiation-PP2A regulatory subunit B55γ. We show that B55γ induced receptor (GR) human primary BM-MSCs during differentiation to osteoblast, but not adipocytes, and required for morphogenesis mineralization....
Two members of the nuclear receptor superfamily, EcR (ecdysteroid protein) and Usp (Ultraspiracle), heterodimerize to form a functional for steroid hormone 20-hydroxyecdysone thus enable it coordinate morphogenetic events during insect metamorphosis. Nterminally Histagged was overexpressed in E. coli cells as nontruncated protein purified homogeneity two chromatographic steps. It demonstrated that recombinant specifically binds ecdysone response element hsp27 gene promoter (hsp27EcRE)....
Sarcomas are a heterogeneous group of mesenchymal orphan cancers and new treatment alternatives beyond traditional chemotherapeutic regimes much needed. So far, tumor mutation analysis has not led to significant advances, we have attempted bypass this limitation by performing direct drug testing library 353 anti-cancer compounds that either FDA-approved, in clinical trial, or advanced stages preclinical development on panel 13 liposarcoma cell lines. We identified validated six drugs,...
Ecdysteroids control molting and metamorphosis in insects via a heterodimeric complex of two nuclear receptors, the ecdysone receptor (EcR) ultraspiracle protein (Usp). We used fluorescence resonance energy transfer (FRET) to study topology natural pseudopalindromic element from hsp27 gene (hsp27pal) with DNA-binding domains Usp EcR (UspDBD EcRDBD, respectively). Steady-state data revealed shortening end-to-end distance hsp27pal-derived probe. For 70.8 ± 0.6 Å obtained for UspDBD-complexed...
Nuclear receptors are ligand-dependent transcription factors responsible for controlling differentiation, growth and development of higher eukaryotes. Three amino acids within the recognition alpha-helix DNA-binding domain nuclear constitute so-called "P-box" which determines response element specificity. In ultraspiracle (Usp) protein, together with EcR forms heterodimeric ecdysone receptor, P-box residues E19, G20 G23. Substitution most characteristic acid estrogen receptor-like P-boxes,...