A5051763115- Biochemical and Molecular Research
- RNA modifications and cancer
- Pluripotent Stem Cells Research
- Cancer, Hypoxia, and Metabolism
- Virus-based gene therapy research
- Cytomegalovirus and herpesvirus research
- Neonatal Health and Biochemistry
- Genomics and Chromatin Dynamics
- Viral-associated cancers and disorders
- Animal Genetics and Reproduction
- Blood disorders and treatments
- HIV/AIDS drug development and treatment
- CRISPR and Genetic Engineering
- Angiogenesis and VEGF in Cancer
- Computational Drug Discovery Methods
- DNA and Nucleic Acid Chemistry
- GDF15 and Related Biomarkers
- Genetics and Neurodevelopmental Disorders
- Biotin and Related Studies
- Glycosylation and Glycoproteins Research
- Cancer Genomics and Diagnostics
- Animal Disease Management and Epidemiology
- Cellular Mechanics and Interactions
- Advanced Biosensing Techniques and Applications
- Retinoids in leukemia and cellular processes
Karolinska Institutet
2012-2023
Weatherford College
2022
Science for Life Laboratory
2021-2022
Background Epstein-Barr virus (EBV) encodes six nuclear transformation-associated proteins that induce extensive changes in cellular gene expression and signaling B-cell transformation. The role of HIF1A EBV-induced immortalization has not been previously studied. Methods Findings Using Western blotting Q-PCR, we found protein is stabilized EBV-transformed lymphoblastoid cells. blotting, GST pulldown assays, immunoprecipitation showed EBV-encoded antigens EBNA-5 EBNA-3 bind to...
Abstract The development of non-genotoxic therapies that activate wild-type p53 in tumors is great interest since the discovery as a tumor suppressor. Here we report identification over 100 small-molecules activating cells. We elucidate mechanism action chiral tetrahydroindazole (HZ00), and through target deconvolution, deduce its active enantiomer ( R )-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). specificity HZ05, more potent analog, revealed by crystal structure )-HZ05/DHODH...
Significance We here describe the essential roles of RB and MRPS18-2 (S18-2) in homeostasis cell stemness. Mouse primary cells expressing both S18-2 (designated as RH18RB) exhibited a stem phenotype. As proof principle, we demonstrated decreased expression stem-cell–related genes human mesenchymal upon down-regulation RB. Notably, loss protein resulted embryonic lethality zebrafish. To reveal putative molecular mechanisms, that S18-2, multimeric complex with RB, enhanced E3-ubiquitin ligase...
Background The Warburg effect is one of the hallmarks cancer and rapidly proliferating cells. It known that hypoxia-inducible factor 1-alpha (HIF1A) MYC proteins cooperatively regulate expression HK2 PDK1 genes, respectively, in Burkitt lymphoma (BL) cell line P493-6, carrying an inducible gene repression system. However, mechanism aerobic glycolysis BL cells has not yet been fully understood. Methods Findings Western blot analysis showed HIF1A protein was highly expressed Epstein–Barr virus...
We report that the overexpression of mitochondrial ribosomal protein MRPS18-2 (S18-2) can immortalize primary rat embryonic fibroblasts (REFs). The immortalized cells (18IM) lose contact inhibition, form foci, and are capable anchorage-independent growth. Concurrently, mesodermal markers, such as vimentin, smooth muscle actin, Fut4, disappear completely. 18IM express stem cell SSEA-1, Sox2, Oct3/4. In confluent cultures, a portion also ectoderm- endoderm-specific pan-keratin,...
We have recently found that primary rat embryonic fibroblasts (REFs) could be immortalized by overexpression of the human mitochondrial ribosomal protein MRPS18-2 (S18-2). A derived cell line, designated 18IM, expressed stem markers SSEA-1 and Sox2. Upon inoculation into severe combined immunodeficiency mice, 18IM cells differentiated to express pan-keratin. They were not tumorigenic. Here we report gene profiling compared with REF cells. Pathways involved in oxidative phosphorylation,...
// Suhas D. Darekar 1 , Muhammad Mushtaq Sreeharsha Gurrapu Larysa Kovalevska 2 Catherine Drummond Maria Petruchek Luca Tirinato 1,3 Enzo Di Fabrizio 3 Ennio Carbone 1,4 and Elena Kashuba 1,2 Department of Microbiology, Tumor Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden R.E. Kavetsky Institute Experimental Pathology, Oncology Radiobiology, NASU, Kiev, Ukraine King Abdullah University Science Technology, PSE BESE Divisions, Thuwal, Kingdom Saudi Arabia 4 "Magna Græcia"...
Dihydroorotate dehydrogenase (DHODH) is essential for the de novo synthesis of pyrimidine ribonucleotides, and as such, its inhibitors have been long used to treat autoimmune diseases are in clinical trials cancer viral infections. Interestingly, DHODH located inner mitochondrial membrane contributes provide ubiquinol respiratory chain. Thus, provides link between nucleotide metabolism function. Here we show that pharmacological inhibition reduces respiration, promotes glycolysis, enhances...
Traditional methods of analytical chemistry to detect an interaction between certain proteins in multicomponent mixtures (e.g. cell lysates, etc.) have limitations. This is due difficulties identification a specific signal analyte (a molecule be detected) against the background. In present work, we propose new protocol for transducer-based sensors with restricted sensitive area. It uses combination analyte–receptor complex precipitation serial additions receptor (CARSAR). To test this...
Human mitochondrial ribosomal protein MRPS18-2 (S18-2) is encoded by a cellular gene that located on the human chromosome 6p21.3. We discovered overexpression of S18-2 led to immortalization and de-differentiation primary rat embryonic fibroblasts. Cells showed anchorage-independent growth pattern. Moreover, pathways characteristic for rapidly proliferating cells were upregulated then. It possible induced disturbance in cell cycle regulation. found cancer lines an appearance multinucleated...
Highly specific and potent inhibitors of dihydroorotate dehydrogenase (DHODH), an essential enzyme the de novo pyrimidine ribonucleotide synthesis pathway, are in clinical trials for autoimmune diseases, viral infections cancer. However, because DHODH (DHODHi) immunosuppressants they may reduce anticancer activity immune system. Therefore, there be a need to improve therapeutic index DHODHi cancer patients. The aim this study was find strategies protect activated T cells from identify types...
Retinoblastoma is an eye cancer that commonly affects young children. Despite significant advances, current treatments cause side effects even when administered locally, and patients may still have to undergo enucleation. This particularly disheartening in cases of bilateral retinoblastoma. Hence, there urgent need for novel therapeutic strategies. Inhibitors the enzyme dihydroorotate dehydrogenase (DHODH), which involved
// Muhammad Mushtaq 1 , Pradeepa N. Pangigadde 1,2 Suhas Darekar Erik Dissen 3 and Elena Kashuba 1,4 Department of Microbiology, Tumor Cell Biology, Karolinska Institutet, Stockholm, Sweden 2 University “Magna Græcia” Catanzaro, Viale Europa, Italy Anatomy, Institute Basic Medical Sciences, Oslo, Norway 4 R.E. Kavetsky Experimental Pathology, Oncology Radiobiology, NASU, Ukraine Correspondence to: Kashuba, email: Keywords : mitochondrial ribosomal protein MRPS18-2, cell...
Abstract Two enzymes involved in the synthesis of pyrimidine and purine nucleotides, CTP synthase (CTPS) IMP dehydrogenase (IMPDH), can assemble into a single or very few large filaments called rods rings (RR) cytoophidia. Most recently, asymmetric cytoplasmic distribution organelles during cell division has been described as decisive event hematopoietic stem fate. We propose that cytoophidia, which could be considered membrane‐less organelles, may also distributed asymmetrically mammalian...
Abstract Highly specific and potent inhibitors of dihydroorotate dehydrogenase (DHODH), an essential enzyme the de novo pyrimidine ribonucleotide synthesis pathway, are in clinical trials for autoimmune diseases, viral infections cancer. However, because DHODH (DHODHi) immunosuppressants they may reduce anticancer activity immune system. Therefore, there be a need to improve therapeutic index DHODHi cancer patients. The aim this study was find strategies protect activated T cells from...