A5028704060- Redox biology and oxidative stress
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Zebrafish Biomedical Research Applications
- Epigenetics and DNA Methylation
- DNA Repair Mechanisms
- Mitochondrial Function and Pathology
- Glutathione Transferases and Polymorphisms
- Glioma Diagnosis and Treatment
- Synthesis and Characterization of Heterocyclic Compounds
- Nanoplatforms for cancer theranostics
- Melanoma and MAPK Pathways
- Sulfur Compounds in Biology
- Neurobiology and Insect Physiology Research
- Mast cells and histamine
- Global Financial Regulation and Crises
- Metalloenzymes and iron-sulfur proteins
- European Monetary and Fiscal Policies
- Genomics, phytochemicals, and oxidative stress
- Immune Cell Function and Interaction
- melanin and skin pigmentation
- Corporate Governance and Law
- Graphene and Nanomaterials Applications
- Protease and Inhibitor Mechanisms
- Synthesis and Reactivity of Sulfur-Containing Compounds
Karolinska Institutet
2015-2024
Svenska Örtmedicinska Institute
2024
Science for Life Laboratory
2014-2021
Södertörn University
2010
Friedrich-Alexander-Universität Erlangen-Nürnberg
1996
The mechanisms by which eukaryotic cells handle and distribute the essential micronutrient iron within cytosol other cellular compartments are only beginning to emerge. yeast monothiol multidomain glutaredoxins (Grx) 3 4 for both transcriptional regulation intracellular distribution. Despite fact that of metabolism differ drastically in fungi higher eukaryotes, conserved, yet their precise function vertebrates has remained elusive. Here we demonstrate a crucial role vertebrate-specific Grx3...
Objective To better comprehend transcriptional phenotypes of cancer cells, we globally characterised RNA-binding proteins (RBPs) to identify altered RNAs, including long non-coding RNAs (lncRNAs). Design unravel RBP-lncRNA interactions in cancer, curated a list ~2300 highly expressed RBPs human tested effects and lncRNAs on patient survival multiple cohorts, expression levels, integrated various sequencing, molecular cell-based data. Results High negatively affected 21 types, especially...
Molecular mechanisms underlying circadian-regulated physiological processes remain largely unknown. Here, we show that disruption of the circadian clock by both constant exposure to light and genetic manipulation key genes in zebrafish led impaired developmental angiogenesis. A bmal1-specific morpholino inhibited angiogenesis embryos without causing obvious nonvascular phenotypes. Conversely, a period2 accelerated angiogenic vessel growth, suggesting Bmal1 Period2 display opposing effects....
Embryonic development depends on complex and precisely orchestrated signaling pathways including specific reduction/oxidation cascades. Oxidoreductases of the thioredoxin family are key players conveying redox signals through reversible posttranslational modifications protein thiols. The importance this during embryogenesis has recently been exemplified for glutaredoxin 2, a vertebrate-specific glutathione-disulfide oxidoreductase with critical role embryonic brain development. Here, we...
Cellular functions and survival are dependent on a tightly controlled redox potential. Currently, an increasing amount of data supports the concept local changes in environment specific signaling events controlling cell function. Specific protein thiol groups major targets regulation. Thioredoxins glutaredoxins catalyze reversible thiol-disulfide exchange reactions primary regulators state. Here, we demonstrate that embryonic brain development depends enzymatic activity glutaredoxin 2....
Abstract The gut microbiome produces metabolites that interact with the aryl hydrocarbon receptor (AhR), a key regulator of immune homoeostasis in 1,2 . Here we show oral exposure to graphene oxide (GO) modulates composition adult zebrafish, significant differences wild-type versus ahr2 -deficient animals. Furthermore, GO was found elicit AhR-dependent induction cyp1a and homing lck + cells germ-free zebrafish larvae when combined short-chain fatty acid butyrate. To obtain further insights...
Glutaredoxin 2 is a vertebrate specific oxidoreductase of the thioredoxin family proteins modulating intracellular thiol pool. Thereby, glutaredoxin important for redox signaling and regulates embryonic development brain vasculature via reversible oxidative posttranslational modifications. Here, we describe that also required successful heart formation. Knock-down in zebrafish embryos inhibits invasion cardiac neural crest cells into primary field. This leads to impaired looping subsequent...
Significance The clinical efficacy of immunotherapy in cancer patients is limited. We have developed a zebrafish model that allows us to visualize the metastatic cell-killing effect by tumor-infiltrating lymphocytes and chimeric antigen receptor T cells vivo at single-cell level. This accurately predicts cell-mediated therapy. Our data provide an platform for validating antimetastatic effects human immunotherapy. Based on our findings, it highly recommended anticancer isolated from or...
Physiological functions of vascular endothelial growth factor (VEGF)-B remain an enigma, and deletion the Vegfb gene in mice lacks overt phenotype. Here we show that knockdown Vegfba, but not Vegfbb, zebrafish embryos by specific morpholinos produced a lethal phenotype owing to neuronal defects brain. Vegfba also markedly prevented development hyaloid vasculatures retina, had little effects on peripheral development. Consistent with phenotypic defects, Vegfaa, mRNA was primarily expressed...
We show for the first time that, in contrast to other glutathione transferases and peroxidases, deletion of microsomal transferase 1 (MGST1) mice is embryonic lethal. To elucidate why, we used zebrafish development as a model system found that knockdown MGST1 produced impaired hematopoiesis. expressed early during plays an important role High expression was detected regions active hematopoiesis co-expressed with markers hematopoietic stem cells. Further, morpholino-mediated knock-down led...
Abstract Cancer cells are commonly in a state of redox imbalance that drives their growth and survival. To compensate for oxidative stress induced by the tumor environment, cancer upregulate specific nononcogenic addiction enzymes, such as MTH1 (NUDT1), which detoxifies oxidized nucleotides. Here, we show increasing nonmalignant sensitization to effects inhibition, whereas decreasing pressure protected against inhibition. Furthermore, purified zebrafish solved crystal structure bound its...
Abstract Background Glioblastoma (GBM) is an aggressive form of brain cancer with poor prognosis. Although murine animal models have given valuable insights into the GBM disease biology, they cannot be used in high-throughput screens to identify and profile novel therapies. The only vertebrate model suitable for large-scale screens, zebrafish, has proven faithfully recapitulate biology pathology human malignancies, clinically relevant orthotopic zebrafish been developed. However, currently...
// Linda Pudelko 1 , Pegah Rouhi 1,5 Kumar Sanjiv Helge Gad Christina Kalderén Andreas Höglund Massimo Squatrito 2 Alberto J. Schuhmacher Steven Edwards 3 Daniel Hägerstrand 4 Ulrika Warpman Berglund Thomas Helleday and Lars Bräutigam Department of Medical Biochemistry Biophysics, Science for Life Laboratory, Division Translational Medicine Chemical Biology, Karolinska Institutet, Stockholm, Sweden Cancer Cell Biology Programme, Seve Ballesteros Foundation Brain Tumor Group, Centro Nacional...
Accumulation of somatic mutations is critical for the transition a normal cell to become cancerous. Mutations cause amino acid substitutions that change properties proteins. However, it has not been studied as what extent composition and accordingly chemical proteome altered result increased mutation load in cancer. Here, we analyzed data on caused by about 2000 protein coding genes from Cancer Cell Line Encyclopedia contains information nucleotide alterations 782 cancer lines, validated...
Graphene oxide (GO) undergoes nitric (NO)-dependent degradation leading to reduced infiltration of polymorphonuclear cells (PMNs) in the GI tract.
Abstract Cutaneous malignant melanoma (CMM) is the deadliest form of skin cancer and clinically challenging due to its propensity develop therapy resistance. Reactive oxygen species (ROS) can induce DNA damage play a significant role in CMM. MTH1 protein protects from ROS often overexpressed different types including Herein, we report that inhibitor TH1579 induced levels, increased responses, caused mitotic arrest suppressed CMM proliferation leading cell death both vitro an vivo xenograft...
The corticotropin-releasing hormone (CRH) family consists of four paralogous genes, CRH and urocortins (UCNs) 1, 2, 3. In a previous study, we analyzed in the teleost model organism zebrafish its transcript distribution embryonic brain. Here, describe full-length cDNAs encoding urotensin 1 (UTS1), UCN1 ortholog, UCN3 zebrafish. Major expression sites uts1 adult are caudal neurosecretory system By using RT-PCR analysis, show that mRNA is also present ovary, maternally contributed to embryo,...
Nucleotides in the free pool are more susceptible to nonenzymatic methylation than those protected DNA double helix. Methylated nucleotides like O6-methyl-dGTP can be mutagenic and toxic if incorporated into DNA. Removal of methylated from nucleotide may therefore important maintain genome integrity. We show that MutT homologue 1 (MTH1) efficiently catalyzes hydrolysis with a catalytic efficiency similar for 8-oxo-dGTP. activity is exclusive MTH1 among human NUDIX proteins conserved through...
Abstract Medulloblastoma (MB) is one of the most common malignant brain tumors in children. Current preclinical vivo model systems for MB have increased our understanding molecular mechanisms regulating development; however, they may not be suitable high-throughput screening efforts. We demonstrate here that transplantation seven different cell lines or patient-derived cells into blastula stage zebrafish embryos leads to orthotopic tumor growth can observed within 24 hours after...
Medulloblastoma (MB) is one of the most common malignant brain tumors in children. Current preclinical vivo model systems for MB have increased our understanding molecular mechanisms regulating development. However, they may not be suitable large-scale studies. The aim this study was to investigate if a zebrafish-based xenograft can recapitulate growth and enable rapid drug testing.