{"entity": "researcher", "timestamp": "2026-07-12T09:10:14.295Z", "family": "Fernandez-Capetillo", "given": "Oscar", "initials": "O", "orcid": "0000-0002-2690-6885", "affiliations": ["Science for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.", "Genomic Instability Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/7134c59abca24f96903fc50914311b40.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/7134c59abca24f96903fc50914311b40"}}, "publications": [{"entity": "publication", "iuid": "3d461197d4a141de8bdde6b2ce2bdfe5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3d461197d4a141de8bdde6b2ce2bdfe5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3d461197d4a141de8bdde6b2ce2bdfe5"}}, "title": "SETD8 inhibition targets cancer cells with increased rates of ribosome biogenesis.", "authors": [{"family": "Murga", "given": "Matilde", "initials": "M"}, {"family": "Lopez-Pernas", "given": "Gema", "initials": "G"}, {"family": "Soliva", "given": "Robert", "initials": "R"}, {"family": "Fueyo-Marcos", "given": "Elena", "initials": "E"}, {"family": "Amor", "given": "Corina", "initials": "C"}, {"family": "Faustino", "given": "Ignacio", "initials": "I"}, {"family": "Serna", "given": "Marina", "initials": "M"}, {"family": "Serrano", "given": "Alicia G", "initials": "AG"}, {"family": "D\u00edaz", "given": "Luc\u00eda", "initials": "L"}, {"family": "Mart\u00ednez", "given": "Sonia", "initials": "S"}, {"family": "Blanco-Aparicio", "given": "Carmen", "initials": "C", "orcid": "0000-0002-3249-6595", "researcher": {"href": "https://publications.scilifelab.se/researcher/e942b8cb061a438086a2824720a610da.json"}}, {"family": "Ant\u00f3n", "given": "Marta Elena", "initials": "ME"}, {"family": "Seashore-Ludlow", "given": "Brinton", "initials": "B"}, {"family": "Pastor", "given": "Joaqu\u00edn", "initials": "J"}, {"family": "Jafari", "given": "Rozbeh", "initials": "R", "orcid": "0000-0002-3396-4709", "researcher": {"href": "https://publications.scilifelab.se/researcher/481b2a2329634f9086cf52fb808edea5.json"}}, {"family": "Lafarga", "given": "Miguel", "initials": "M"}, {"family": "Llorca", "given": "Oscar", "initials": "O", "orcid": "0000-0001-5705-0699", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f79b00a799744b2b513ebd696b0f357.json"}}, {"family": "Orozco", "given": "Modesto", "initials": "M"}, {"family": "Fern\u00e1ndez-Capetillo", "given": "Oscar", "initials": "O", "orcid": "0000-0002-2690-6885", "researcher": {"href": "https://publications.scilifelab.se/researcher/7134c59abca24f96903fc50914311b40.json"}}], "type": "journal article", "published": "2024-09-28", "journal": {"title": "Cell Death Dis", "issn": "2041-4889", "volume": "15", "issue": "9", "pages": "694", "issn-l": "2041-4889"}, "abstract": "SETD8 is a methyltransferase that is overexpressed in several cancers, which monomethylates H4K20 as well as other non-histone targets such as PCNA or p53. We here report novel SETD8 inhibitors, which were discovered while trying to identify chemicals that prevent 53BP1 foci formation, an event mediated by H4K20 methylation. Consistent with previous reports, SETD8 inhibitors induce p53 expression, although they are equally toxic for p53 proficient or deficient cells. Thermal stability proteomics revealed that the compounds had a particular impact on nucleoli, which was confirmed by fluorescent and electron microscopy. Similarly, Setd8 deletion generated nucleolar stress and impaired ribosome biogenesis, supporting that this was an on-target effect of SETD8 inhibitors. Furthermore, a genome-wide CRISPR screen identified an enrichment of nucleolar factors among those modulating the toxicity of SETD8 inhibitors. Accordingly, the toxicity of SETD8 inhibition correlated with MYC or mTOR activity, key regulators of ribosome biogenesis. Together, our study provides a new class of SETD8 inhibitors and a novel biomarker to identify tumors most likely to respond to this therapy.", "doi": "10.1038/s41419-024-07106-6", "pmid": "39341827", "labels": {"Global Proteomics and Proteogenomics": "Service", "Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11438997"}, {"db": "pii", "key": "10.1038/s41419-024-07106-6"}], "notes": [], "created": "2024-11-27T13:00:41.430Z", "modified": "2025-10-17T13:04:27.192Z"}, {"entity": "publication", "iuid": "ca2b4c271c3044e4bd9b00a8da9cb717", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ca2b4c271c3044e4bd9b00a8da9cb717.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ca2b4c271c3044e4bd9b00a8da9cb717"}}, "title": "The anti-leprosy drug clofazimine reduces polyQ toxicity through activation of PPAR", "authors": [{"family": "Li", "given": "Xuexin", "initials": "X"}, {"family": "Hernandez", "given": "Ivo", "initials": "I"}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M", "orcid": "0000-0002-3857-1437", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2b5f5d0486a4422b93a626a2cd1583f.json"}}, {"family": "Lidemalm", "given": "Louise", "initials": "L"}, {"family": "Brautigam", "given": "Lars", "initials": "L"}, {"family": "Lucas", "given": "Jose J", "initials": "JJ"}, {"family": "Carreras-Puigvert", "given": "Jordi", "initials": "J", "orcid": "0000-0002-7671-3707", "researcher": {"href": "https://publications.scilifelab.se/researcher/28ad5f6a1a064e52aca72780adc4bb96.json"}}, {"family": "H\u00fchn", "given": "Daniela", "initials": "D"}, {"family": "Fernandez-Capetillo", "given": "Oscar", "initials": "O", "orcid": "0000-0002-2690-6885", "researcher": {"href": "https://publications.scilifelab.se/researcher/7134c59abca24f96903fc50914311b40.json"}}], "type": "posted-content", "published": "2023-02-06", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2023.02.06.527298", "pmid": null, "labels": {"Chemical Biology Consortium Sweden": "Service"}, "xrefs": [], "notes": [], "created": "2023-10-18T18:42:14.701Z", "modified": "2025-12-18T19:55:52.283Z"}, {"entity": "publication", "iuid": "701785c017b4467aa1398c5cd72ffc34", "links": {"self": {"href": "https://publications.scilifelab.se/publication/701785c017b4467aa1398c5cd72ffc34.json"}, "display": {"href": "https://publications.scilifelab.se/publication/701785c017b4467aa1398c5cd72ffc34"}}, "title": "New regulators of the tetracycline\u2010inducible gene expression system identified by chemical and genetic screens", "authors": [{"family": "Colicchia", "given": "Valeria", "initials": "V", "orcid": "0000-0001-5290-5379", "researcher": {"href": "https://publications.scilifelab.se/researcher/7207b5c69fdc4b94a2b9edbf78725504.json"}}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M"}, {"family": "Sirozh", "given": "Oleksandra", "initials": "O"}, {"family": "Porebski", "given": "Bartlomiej", "initials": "B"}, {"family": "Balan", "given": "Mirela", "initials": "M"}, {"family": "Li", "given": "Xuexin", "initials": "X", "orcid": "0000-0001-5824-9720", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfd5f1e6e5644a9ab922a685167f868d.json"}}, {"family": "Lidemalm", "given": "Louise", "initials": "L"}, {"family": "Carreras\u2010Puigvert", "given": "Jordi", "initials": "J"}, {"family": "H\u00fchn", "given": "Daniela", "initials": "D"}, {"family": "Fernandez\u2010Capetillo", "given": "Oscar", "initials": "O", "orcid": "0000-0002-2690-6885", "researcher": {"href": "https://publications.scilifelab.se/researcher/7134c59abca24f96903fc50914311b40.json"}}], "type": "journal-article", "published": "2022-10-00", "journal": {"title": "FEBS Open Bio", "issn": "2211-5463", "issn-l": null, "volume": "12", "issue": "10", "pages": "1896-1908"}, "abstract": "The tetracycline repressor (tetR)-regulated system is a widely used tool to specifically control gene expression in mammalian cells. Based on this system, we generated a human osteosarcoma cell line, which allows for the inducible expression of an EGFP fusion of the TAR DNA-binding protein 43 (TDP-43), which has been linked to neurodegenerative diseases. Consistent with previous findings, TDP-43 overexpression led to the accumulation of aggregates and limited the viability of U2OS. Using this inducible system, we conducted a chemical screen with a library that included FDA-approved drugs. While the primary screen identified several compounds that prevented TDP-43 toxicity, further experiments revealed that these chemicals abrogated the doxycycline-dependent TDP-43 expression. This antagonistic effect was observed with both doxycycline and tetracycline, and in several Tet-On cell lines expressing different genes, confirming the general effect of these compounds as inhibitors of the tetR system. Using the same cell line, a genome-wide CRISPR/Cas9 screen identified epigenetic regulators such as the G9a methyltransferase and TRIM28 as potential modifiers of TDP-43 toxicity. Yet again, further experiments revealed that G9a inhibition or TRIM28 loss prevented doxycycline-dependent expression of TDP-43. In summary, we have identified new chemical and genetic regulators of the tetR system, thereby raising awareness of the limitations of this approach to conduct chemical or genetic screening in mammalian cells.", "doi": "10.1002/2211-5463.13482", "pmid": "36062323", "labels": {"CRISPR Functional Genomics": "Service", "Chemical Biology Consortium Sweden": "Service"}, "xrefs": [], "notes": [], "created": "2022-09-13T07:22:59.485Z", "modified": "2025-10-17T13:04:27.818Z"}, {"entity": "publication", "iuid": "b2805e31dce94755af4fde64db297814", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b2805e31dce94755af4fde64db297814.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b2805e31dce94755af4fde64db297814"}}, "title": "Prolonged estrogen deprivation triggers a broad immunosuppressive phenotype in breast cancer cells", "authors": [{"family": "H\u00fchn", "given": "Daniela", "initials": "D"}, {"family": "Mart\u00ed\u2010Rodrigo", "given": "Pablo", "initials": "P", "orcid": "0000-0002-1049-0918", "researcher": {"href": "https://publications.scilifelab.se/researcher/e63e9b1775f046ed8c8feb106f8cebca.json"}}, {"family": "Mouron", "given": "Silvana", "initials": "S"}, {"family": "Hansel", "given": "Catherine", "initials": "C"}, {"family": "Tschapalda", "given": "Kirsten", "initials": "K"}, {"family": "Porebski", "given": "Bartlomiej", "initials": "B"}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M"}, {"family": "Lidemalm", "given": "Louise", "initials": "L"}, {"family": "Quintela\u2010Fandino", "given": "Miguel", "initials": "M"}, {"family": "Carreras\u2010Puigvert", "given": "Jordi", "initials": "J"}, {"family": "Fernandez\u2010Capetillo", "given": "Oscar", "initials": "O", "orcid": "0000-0002-2690-6885", "researcher": {"href": "https://publications.scilifelab.se/researcher/7134c59abca24f96903fc50914311b40.json"}}], "type": "journal-article", "published": "2022-01-00", "journal": {"title": "Mol Oncol", "issn": "1574-7891", "issn-l": null, "volume": "16", "issue": "1", "pages": "148-165"}, "abstract": null, "doi": "10.1002/1878-0261.13083", "pmid": null, "labels": {"Chemical Biology Consortium Sweden": "Service"}, "xrefs": [], "notes": [], "created": "2019-11-28T13:54:09.398Z", "modified": "2025-10-17T13:04:27.970Z"}, {"entity": "publication", "iuid": "99bbc9211a014ec2a9ee1106611e757c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/99bbc9211a014ec2a9ee1106611e757c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/99bbc9211a014ec2a9ee1106611e757c"}}, "title": "Prolonged estrogen deprivation triggers a broad immunosuppressive phenotype in breast cancer cells.", "authors": [{"family": "H\u00fchn", "given": "Daniela", "initials": "D"}, {"family": "Mart\u00ed-Rodrigo", "given": "Pablo", "initials": "P", "orcid": "0000-0002-1049-0918", "researcher": {"href": "https://publications.scilifelab.se/researcher/e63e9b1775f046ed8c8feb106f8cebca.json"}}, {"family": "Mouron", "given": "Silvana", "initials": "S"}, {"family": "Hansel", "given": "Catherine", "initials": "C"}, {"family": "Tschapalda", "given": "Kirsten", "initials": "K"}, {"family": "Porebski", "given": "Bartlomiej", "initials": "B"}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M"}, {"family": "Lidemalm", "given": "Louise", "initials": "L"}, {"family": "Quintela-Fandino", "given": "Miguel", "initials": "M"}, {"family": "Carreras-Puigvert", "given": "Jordi", "initials": "J"}, {"family": "Fernandez-Capetillo", "given": "Oscar", "initials": "O", "orcid": "0000-0002-2690-6885", "researcher": {"href": "https://publications.scilifelab.se/researcher/7134c59abca24f96903fc50914311b40.json"}}], "type": "journal article", "published": "2021-08-15", "journal": {"title": "Mol Oncol", "issn": "1878-0261", "issn-l": "1574-7891", "volume": null, "issue": null, "pages": null}, "abstract": "Among others, expression levels of programmed cell death 1 ligand 1 (PD-L1) have been explored as biomarkers of the response to immune checkpoint inhibitors in cancer therapy. Here, we present the results of a chemical screen that interrogated how medically approved drugs influence PD-L1 expression. As expected, corticosteroids and inhibitors of Janus kinases were among the top PD-L1 downregulators. In addition, we identified that PD-L1 expression is induced by antiestrogenic compounds. Transcriptomic analyses indicate that chronic estrogen receptor alpha (ER\u03b1) inhibition triggers a broad immunosuppressive program in ER-positive breast cancer cells, which is subsequent to their growth arrest and involves the activation of multiple immune checkpoints together with the silencing of the antigen-presenting machinery. Accordingly, estrogen-deprived MCF7 cells are resistant to T-cell-mediated cell killing, in a manner that is independent of PD-L1, but which is reverted by estradiol. Our study reveals that while antiestrogen therapies efficiently limit the growth of ER-positive breast cancer cells, they concomitantly trigger a transcriptional program that favors their immune evasion.", "doi": "10.1002/1878-0261.13083", "pmid": "34392603", "labels": {"Chemical Biology Consortium Sweden": "Service"}, "xrefs": [], "notes": [], "created": "2021-11-18T11:57:22.385Z", "modified": "2025-10-17T13:04:28.053Z"}, {"entity": "publication", "iuid": "2408a212215347ec8d1116439307bfbc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2408a212215347ec8d1116439307bfbc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2408a212215347ec8d1116439307bfbc"}}, "title": "A chemical screen for modulators of mRNA translation identifies a distinct mechanism of toxicity for sphingosine kinase inhibitors.", "authors": [{"family": "Corman", "given": "Alba", "initials": "A", "orcid": "0000-0001-8133-8967", "researcher": {"href": "https://publications.scilifelab.se/researcher/0a5a2d2944fb424d8a5e10c3f82ca35f.json"}}, {"family": "Kanellis", "given": "Dimitris C", "initials": "DC"}, {"family": "Michalska", "given": "Patrycja", "initials": "P"}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M", "orcid": "0000-0002-3857-1437", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2b5f5d0486a4422b93a626a2cd1583f.json"}}, {"family": "Lafarga", "given": "Vanesa", "initials": "V"}, {"family": "Bartek", "given": "Jiri", "initials": "J"}, {"family": "Carreras-Puigvert", "given": "Jordi", "initials": "J", "orcid": "0000-0002-7671-3707", "researcher": {"href": "https://publications.scilifelab.se/researcher/28ad5f6a1a064e52aca72780adc4bb96.json"}}, {"family": "Fernandez-Capetillo", "given": "Oscar", "initials": "O", "orcid": "0000-0002-2690-6885", "researcher": {"href": "https://publications.scilifelab.se/researcher/7134c59abca24f96903fc50914311b40.json"}}], "type": "journal article", "published": "2021-05-00", "journal": {"title": "PLoS Biol.", "issn": "1545-7885", "issn-l": "1544-9173", "volume": "19", "issue": "5", "pages": "e3001263"}, "abstract": "We here conducted an image-based chemical screen to evaluate how medically approved drugs, as well as drugs that are currently under development, influence overall translation levels. None of the compounds up-regulated translation, which could be due to the screen being performed in cancer cells grown in full media where translation is already present at very high levels. Regarding translation down-regulators, and consistent with current knowledge, inhibitors of the mechanistic target of rapamycin (mTOR) signaling pathway were the most represented class. In addition, we identified that inhibitors of sphingosine kinases (SPHKs) also reduce mRNA translation levels independently of mTOR. Mechanistically, this is explained by an effect of the compounds on the membranes of the endoplasmic reticulum (ER), which activates the integrated stress response (ISR) and contributes to the toxicity of SPHK inhibitors. Surprisingly, the toxicity and activation of the ISR triggered by 2 independent SPHK inhibitors, SKI-II and ABC294640, the latter in clinical trials, are also observed in cells lacking SPHK1 and SPHK2. In summary, our study provides a useful resource on the effects of medically used drugs on translation, identified compounds capable of reducing translation independently of mTOR and has revealed that the cytotoxic properties of SPHK inhibitors being developed as anticancer agents are independent of SPHKs.", "doi": "10.1371/journal.pbio.3001263", "pmid": "34033645", "labels": {"Chemical Biology Consortium Sweden": "Service"}, "xrefs": [{"db": "pii", "key": "PBIOLOGY-D-20-02267"}, {"db": "pmc", "key": "PMC8183993"}], "notes": [], "created": "2021-11-18T11:58:16.393Z", "modified": "2025-10-17T13:04:28.111Z"}]}