{"entity": "researcher", "timestamp": "2026-08-11T14:11:10.989Z", "family": "H\u00e4ggblad", "given": "Maria", "initials": "M", "orcid": "0000-0002-3857-1437", "affiliations": ["Science for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/c2b5f5d0486a4422b93a626a2cd1583f.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/c2b5f5d0486a4422b93a626a2cd1583f"}}, "publications": [{"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": "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"}, {"entity": "publication", "iuid": "675347d3c50d42f196d814d845d3b268", "links": {"self": {"href": "https://publications.scilifelab.se/publication/675347d3c50d42f196d814d845d3b268.json"}, "display": {"href": "https://publications.scilifelab.se/publication/675347d3c50d42f196d814d845d3b268"}}, "title": "MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool.", "authors": [{"family": "Gad", "given": "Helge", "initials": "H", "orcid": "0000-0001-6530-1443", "researcher": {"href": "https://publications.scilifelab.se/researcher/6273ef3dd1574185af0a83e9ab31bfe5.json"}}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "A", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd07c6c543544af1a904e039f73ba857.json"}}, {"family": "Eshtad", "given": "Saeed", "initials": "S", "orcid": "0000-0001-6763-4700", "researcher": {"href": "https://publications.scilifelab.se/researcher/edf4a705cae045feb64d1d9c7f8d9646.json"}}, {"family": "Jacques", "given": "Sylvain A", "initials": "SA"}, {"family": "Str\u00f6m", "given": "Cecilia E", "initials": "CE"}, {"family": "Svensson", "given": "Linda M", "initials": "LM"}, {"family": "Schultz", "given": "Niklas", "initials": "N"}, {"family": "Lundb\u00e4ck", "given": "Thomas", "initials": "T", "orcid": "0000-0002-8145-7808", "researcher": {"href": "https://publications.scilifelab.se/researcher/e13df787cb884549bcf333aba4e6f010.json"}}, {"family": "Einarsdottir", "given": "Berglind Osk", "initials": "BO"}, {"family": "Saleh", "given": "Aljona", "initials": "A"}, {"family": "G\u00f6kt\u00fcrk", "given": "Camilla", "initials": "C", "orcid": "0000-0002-6272-9927", "researcher": {"href": "https://publications.scilifelab.se/researcher/9318cec5020f4c92b8393b20242c0d58.json"}}, {"family": "Baranczewski", "given": "Pawel", "initials": "P", "orcid": "0000-0001-5772-6791", "researcher": {"href": "https://publications.scilifelab.se/researcher/47f7af2466c14275a42aad4a431b2dcb.json"}}, {"family": "Svensson", "given": "Richard", "initials": "R"}, {"family": "Berntsson", "given": "Ronnie P-A", "initials": "RP"}, {"family": "Gustafsson", "given": "Robert", "initials": "R", "orcid": "0000-0002-4854-5531", "researcher": {"href": "https://publications.scilifelab.se/researcher/16dd7e73adad4f85972d1d546bfa6d2a.json"}}, {"family": "Str\u00f6mberg", "given": "Kia", "initials": "K"}, {"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Jacques-Cordonnier", "given": "Marie-Caroline", "initials": "M"}, {"family": "Desroses", "given": "Matthieu", "initials": "M", "orcid": "0000-0003-4152-3855", "researcher": {"href": "https://publications.scilifelab.se/researcher/b232b70751004e9ea6b547533f901376.json"}}, {"family": "Gustavsson", "given": "Anna-Lena", "initials": "A", "orcid": "0000-0003-4332-2336", "researcher": {"href": "https://publications.scilifelab.se/researcher/6b014ef7ea0d461b8e2ddb87506b1252.json"}}, {"family": "Olofsson", "given": "Roger", "initials": "R"}, {"family": "Johansson", "given": "Fredrik", "initials": "F", "orcid": "0000-0001-5160-9543", "researcher": {"href": "https://publications.scilifelab.se/researcher/0667c14b327f44fd8a802acd9c3f1fb2.json"}}, {"family": "Homan", "given": "Evert J", "initials": "EJ"}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Br\u00e4utigam", "given": "Lars", "initials": "L"}, {"family": "Johansson", "given": "Lars", "initials": "L", "orcid": "0000-0001-7071-4699", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b9129e8ce7846e5b35b50f1ff4493e2.json"}}, {"family": "H\u00f6glund", "given": "Andreas", "initials": "A", "orcid": "0000-0002-1130-374X", "researcher": {"href": "https://publications.scilifelab.se/researcher/70a484451caf40f2a1a196b36bb9c423.json"}}, {"family": "Hagenkort", "given": "Anna", "initials": "A"}, {"family": "Pham", "given": "Therese", "initials": "T"}, {"family": "Altun", "given": "Mikael", "initials": "M", "orcid": "0000-0002-6937-6124", "researcher": {"href": "https://publications.scilifelab.se/researcher/4317b773615e476694840e907b7b1a0c.json"}}, {"family": "Gaugaz", "given": "Fabienne Z", "initials": "FZ"}, {"family": "Vikingsson", "given": "Svante", "initials": "S"}, {"family": "Evers", "given": "Bastiaan", "initials": "B"}, {"family": "Henriksson", "given": "Martin", "initials": "M"}, {"family": "Vallin", "given": "Karl S A", "initials": "KSA"}, {"family": "Wallner", "given": "Olov A", "initials": "OA"}, {"family": "Hammarstr\u00f6m", "given": "Lars G J", "initials": "LGJ"}, {"family": "Wiita", "given": "Elisee", "initials": "E"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Kalder\u00e9n", "given": "Christina", "initials": "C"}, {"family": "Axelsson", "given": "Hanna", "initials": "H", "orcid": "0000-0003-2365-1749", "researcher": {"href": "https://publications.scilifelab.se/researcher/63b88c4d11c443f39121c6d93fcff1f0.json"}}, {"family": "Djureinovic", "given": "Tatjana", "initials": "T"}, {"family": "Puigvert", "given": "Jordi Carreras", "initials": "JC"}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M", "orcid": "0000-0002-3857-1437", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2b5f5d0486a4422b93a626a2cd1583f.json"}}, {"family": "Jeppsson", "given": "Fredrik", "initials": "F"}, {"family": "Martens", "given": "Ulf", "initials": "U"}, {"family": "Lundin", "given": "Cecilia", "initials": "C"}, {"family": "Lundgren", "given": "Bo", "initials": "B"}, {"family": "Granelli", "given": "Ingrid", "initials": "I"}, {"family": "Jensen", "given": "Annika Jenmalm", "initials": "AJ"}, {"family": "Artursson", "given": "Per", "initials": "P", "orcid": "0000-0002-3708-7395", "researcher": {"href": "https://publications.scilifelab.se/researcher/31575936c2714e1eb2f35c12df9a65a8.json"}}, {"family": "Nilsson", "given": "Jonas A", "initials": "JA", "orcid": "0000-0003-0346-6837", "researcher": {"href": "https://publications.scilifelab.se/researcher/27f0581f25124e98b0bd0eef8c3f3331.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97eba9f5edf4d76a5259c4baa8366c5.json"}}, {"family": "Scobie", "given": "Martin", "initials": "M", "orcid": "0000-0002-7073-8495", "researcher": {"href": "https://publications.scilifelab.se/researcher/87c041a8b3414f5db02873dc8013806b.json"}}, {"family": "Berglund", "given": "Ulrika Warpman", "initials": "UW", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications.scilifelab.se/researcher/a74c79d4b11346a4918f536b5a678e12.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}], "type": "journal article", "published": "2014-04-10", "journal": {"volume": "508", "issn": "1476-4687", "issue": "7495", "pages": "215-221", "title": "Nature", "issn-l": "0028-0836"}, "abstract": "Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bind in the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.", "doi": "10.1038/nature13181", "pmid": "24695224", "labels": {"Protein Science Facility (PSF)": null, "Chemical Biology Consortium Sweden": "Collaborative", "Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pii", "key": "nature13181"}], "notes": "Uppsala Drug Optimization and Pharmaceutical Profiling (UDOPP)\r\nADME of Therapeutics (UDOPP)\r\nBiochemical and Cellular Screening", "created": "2017-05-04T14:56:52.658Z", "modified": "2025-10-23T08:56:28.795Z"}, {"entity": "publication", "iuid": "e9c9a297dc294e8a9b7a9be667c54458", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e9c9a297dc294e8a9b7a9be667c54458.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e9c9a297dc294e8a9b7a9be667c54458"}}, "title": "Comparative drug pair screening across multiple glioblastoma cell lines reveals novel drug-drug interactions.", "authors": [{"family": "Schmidt", "given": "Linn\u00e9a", "initials": "L"}, {"family": "Kling", "given": "Teresia", "initials": "T"}, {"family": "Monsefi", "given": "Naser", "initials": "N"}, {"family": "Olsson", "given": "Maja", "initials": "M"}, {"family": "Hansson", "given": "Caroline", "initials": "C", "orcid": "0000-0001-6738-6495", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f707f6560ae4e948196bf0f5abfa36f.json"}}, {"family": "Baskaran", "given": "Sathishkumar", "initials": "S"}, {"family": "Lundgren", "given": "Bo", "initials": "B"}, {"family": "Martens", "given": "Ulf", "initials": "U"}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M", "orcid": "0000-0002-3857-1437", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2b5f5d0486a4422b93a626a2cd1583f.json"}}, {"family": "Westermark", "given": "Bengt", "initials": "B", "orcid": "0000-0001-7153-5545", "researcher": {"href": "https://publications.scilifelab.se/researcher/dbaf3a1cdd7d48e5ba9e147bfb5055b6.json"}}, {"family": "Forsberg Nilsson", "given": "Karin", "initials": "K"}, {"family": "Uhrbom", "given": "Lene", "initials": "L", "orcid": "0000-0001-8595-5698", "researcher": {"href": "https://publications.scilifelab.se/researcher/67bb8672ad514a9bb5f86c8d6b494269.json"}}, {"family": "Karlsson-Lindahl", "given": "Linda", "initials": "L"}, {"family": "Gerlee", "given": "Philip", "initials": "P"}, {"family": "Nelander", "given": "Sven", "initials": "S", "orcid": "0000-0003-1758-1262", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d684fc3b26d4741b850790ba0571c96.json"}}], "type": "journal article", "published": "2013-11-00", "journal": {"volume": "15", "issn": "1523-5866", "issue": "11", "pages": "1469-1478", "title": "Neuro-oncology", "issn-l": "1522-8517"}, "abstract": "Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults, and despite state-of-the-art treatment, survival remains poor and novel therapeutics are sorely needed. The aim of the present study was to identify new synergistic drug pairs for GBM. In addition, we aimed to explore differences in drug-drug interactions across multiple GBM-derived cell cultures and predict such differences by use of transcriptional biomarkers.\r\n\r\nWe performed a screen in which we quantified drug-drug interactions for 465 drug pairs in each of the 5 GBM cell lines U87MG, U343MG, U373MG, A172, and T98G. Selected interactions were further tested using isobole-based analysis and validated in 5 glioma-initiating cell cultures. Furthermore, drug interactions were predicted using microarray-based transcriptional profiling in combination with statistical modeling.\r\n\r\nOf the 5 \u00d7 465 drug pairs, we could define a subset of drug pairs with strong interaction in both standard cell lines and glioma-initiating cell cultures. In particular, a subset of pairs involving the pharmaceutical compounds rimcazole, sertraline, pterostilbene, and gefitinib showed a strong interaction in a majority of the cell cultures tested. Statistical modeling of microarray and interaction data using sparse canonical correlation analysis revealed several predictive biomarkers, which we propose could be of importance in regulating drug pair responses.\r\n\r\nWe identify novel candidate drug pairs for GBM and suggest possibilities to prospectively use transcriptional biomarkers to predict drug interactions in individual cases.", "doi": "10.1093/neuonc/not111", "pmid": "24101737", "labels": {"Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pii", "key": "not111"}, {"db": "pmc", "key": "PMC3813417"}], "notes": "Biochemical and Cellular Screening", "created": "2017-05-04T14:57:02.204Z", "modified": "2025-10-23T08:55:35.813Z"}]}