{"entity": "researcher", "timestamp": "2026-08-20T20:48:58.451Z", "family": "Herold", "given": "Nikolas", "initials": "N", "orcid": "0000-0001-9468-4543", "affiliations": ["Division of Pediatric Oncology and Surgery, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.", "Pediatric Oncology, Astrid Lindgren's Children's Hospital, Karolinska University Hospital, Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/749eedaa5f69414aa315bb875eef9475.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/749eedaa5f69414aa315bb875eef9475"}}, "publications": [{"entity": "publication", "iuid": "4fa302a131c347a4967d5d96e978a559", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/4fa302a131c347a4967d5d96e978a559.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/4fa302a131c347a4967d5d96e978a559"}}, "title": "SF3B1-mutant models of RNA mis-splicing uncover UBA1 as a therapeutic target in myelodysplastic neoplasms.", "authors": [{"family": "Thier", "given": "Jonas", "initials": "J", "orcid": "0009-0007-5226-0372", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2670901806e94464820ea6749c625a41.json"}}, {"family": "Hofmann", "given": "Sophia", "initials": "S", "orcid": "0009-0006-6625-8348", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5299df88b9d04e93b39f5a2ec32f4e26.json"}}, {"family": "Kirchhof", "given": "Katharina M", "initials": "KM", "orcid": "0000-0001-8412-4585", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6fd0174077664b6c94b948c4b6f97346.json"}}, {"family": "Todisco", "given": "Gabriele", "initials": "G", "orcid": "0000-0001-6583-3829", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/769f70d382bc46cfbfffa0b5cd16710f.json"}}, {"family": "Mortera-Blanco", "given": "Teresa", "initials": "T", "orcid": "0000-0002-8399-1430", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2afa2c9bceb44bd7aa4810e7846b5607.json"}}, {"family": "Lilienthal", "given": "Ingrid", "initials": "I", "orcid": "0000-0001-5270-7268", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5831c58c547d47f9826997c52763a30b.json"}}, {"family": "Kanellis", "given": "Dimitris C", "initials": "DC", "orcid": "0000-0001-8690-2010", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/14307e4299ce40a49d2e45265398676c.json"}}, {"family": "Barbosa", "given": "Indira", "initials": "I", "orcid": "0009-0004-1171-2932", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2c92d74875a9433fafc001f47e3f48c3.json"}}, {"family": "Bj\u00f6rklund", "given": "Ann-Charlotte", "initials": "AC", "orcid": "0009-0008-3745-503X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2646432d278e40b79a75cbb5222ceb39.json"}}, {"family": "Deslauriers", "given": "Andr\u00e9 G", "initials": "AG", "orcid": "0000-0002-2854-5681", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2bcb1a0e3ce6438ab3aec7e24a383d3a.json"}}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/288939950c0c4c6393d35c84e5128b5f.json"}}, {"family": "Herold", "given": "Nikolas", "initials": "N", "orcid": "0000-0001-9468-4543", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/749eedaa5f69414aa315bb875eef9475.json"}}, {"family": "Papaemmanuil", "given": "Elli", "initials": "E", "orcid": "0000-0003-1709-8983", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6ea61c4aa9324a398fffe747c0e7824d.json"}}, {"family": "Papapetrou", "given": "Eirini P", "initials": "EP", "orcid": "0000-0001-7002-417X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7951631751334226bc25259c6af73da8.json"}}, {"family": "Hellstr\u00f6m-Lindberg", "given": "Eva", "initials": "E", "orcid": "0000-0002-7839-3743", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/66eecd3e3886496cb7f7dcaefa5e6a36.json"}}, {"family": "Moura", "given": "Pedro L", "initials": "PL", "orcid": "0000-0002-0493-5394", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ac418bab887f4153b20d77dfc455b3a7.json"}}, {"family": "Lundin", "given": "Vanessa", "initials": "V", "orcid": "0000-0003-2335-3370", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9b746851c7044c7f8563cc39ed9f457e.json"}}], "type": "journal article", "published": "2025-11-00", "journal": {"title": "Leukemia", "issn": "1476-5551", "volume": "39", "issue": "11", "pages": "2801-2811", "issn-l": "0887-6924"}, "abstract": "Myelodysplastic syndromes with somatic mutations in the splicing factor SF3B1 gene (MDS-SF3B1) result in RNA mis-splicing, erythroid dysplasia and ultimately refractory anemia. Precision medicine approaches for MDS-SF3B1 remain challenging due to both the complexity of the mis-splicing landscape and its evaluation in disease-accurate models. To uncover novel RNA mis-splicing events, isogenic SF3B1K700E and SF3B1WT iPSC lines from an MDS-SF3B1 patient were differentiated into hematopoietic cells and analyzed via unsupervised splicing event profiling using full-length RNA sequencing. This identified SF3B1K700E-specific mis-splicing of ubiquitin-like modifier activating enzyme 1 (UBA1), which encodes a key E1 protein at the apex of the ubiquitination cascade. UBA1 mis-splicing (UBA1ms) introduced protein instability and decreased total UBA1 levels, rendering mutated cells susceptible to the small-molecule UBA1 inhibitor TAK-243. Analysis of CD34+ RNA sequencing data from an MDS patient cohort confirmed unique and ubiquitous UBA1ms in MDS-SF3B1 patients, absent in other splicing factor-mutated MDS cases or healthy controls. TAK-243 selectively targeted MDS-SF3B1 primary CD34+ cells and reduced mutant cell numbers in colony-forming assays. In contrast, normal hematopoietic progenitor cells were unaffected. Altogether, we here define UBA1ms as a novel therapeutic vulnerability in SF3B1-mutant cells, introducing UBA1 inhibition as a potential avenue for future MDS-SF3B1 treatments.", "doi": "10.1038/s41375-025-02740-1", "pmid": "40858805", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12589102"}, {"db": "pii", "key": "10.1038/s41375-025-02740-1"}], "notes": [], "created": "2026-08-20T08:47:24.962Z", "modified": "2026-08-20T08:47:51.017Z"}, {"entity": "publication", "iuid": "ad8c0e59f9c1458793d5a1182228a464", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/ad8c0e59f9c1458793d5a1182228a464.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/ad8c0e59f9c1458793d5a1182228a464"}}, "title": "Nucleobase and Nucleoside Analogues: Resistance and Re-Sensitisation at the Level of Pharmacokinetics, Pharmacodynamics and Metabolism.", "authors": [{"family": "Tsesmetzis", "given": "Nikolaos", "initials": "N"}, {"family": "Paulin", "given": "Cynthia B J", "initials": "CBJ"}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}, {"family": "Herold", "given": "Nikolas", "initials": "N", "orcid": "0000-0001-9468-4543", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/749eedaa5f69414aa315bb875eef9475.json"}}], "type": "journal article", "published": "2018-07-23", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "10", "issue": "7", "issn-l": "2072-6694"}, "abstract": "Antimetabolites, in particular nucleobase and nucleoside analogues, are cytotoxic drugs that, starting from the small field of paediatric oncology, in combination with other chemotherapeutics, have revolutionised clinical oncology and transformed cancer into a curable disease. However, even though combination chemotherapy, together with radiation, surgery and immunotherapy, can nowadays cure almost all types of cancer, we still fail to achieve this for a substantial proportion of patients. The understanding of differences in metabolism, pharmacokinetics, pharmacodynamics, and tumour biology between patients that can be cured and patients that cannot, builds the scientific basis for rational therapy improvements. Here, we summarise current knowledge of how tumour-specific and patient-specific factors can dictate resistance to nucleobase/nucleoside analogues, and which strategies of re-sensitisation exist. We revisit well-established hurdles to treatment efficacy, like the blood-brain barrier and reduced deoxycytidine kinase activity, but will also discuss the role of novel resistance factors, such as SAMHD1. A comprehensive appreciation of the complex mechanisms that underpin the failure of chemotherapy will hopefully inform future strategies of personalised medicine.", "doi": "10.3390/cancers10070240", "pmid": "30041457", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6071274"}, {"db": "pii", "key": "cancers10070240"}], "notes": [], "created": "2026-08-20T13:39:10.206Z", "modified": "2026-08-20T13:39:10.275Z"}, {"entity": "publication", "iuid": "239b778e2e954ecf8a5d32bbc4735453", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/239b778e2e954ecf8a5d32bbc4735453.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/239b778e2e954ecf8a5d32bbc4735453"}}, "title": "SAMHD1 is a barrier to antimetabolite-based cancer therapies.", "authors": [{"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}, {"family": "Schaller", "given": "Torsten", "initials": "T", "orcid": "0000-0001-9597-4112", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/93d3003ec7854be68f4e38283bca1da0.json"}}, {"family": "Herold", "given": "Nikolas", "initials": "N", "orcid": "0000-0001-9468-4543", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/749eedaa5f69414aa315bb875eef9475.json"}}], "type": "journal article", "published": "2017-02-03", "journal": {"title": "Mol Cell Oncol", "issn": "2372-3556", "volume": "4", "issue": "2", "pages": "e1287554", "issn-l": null}, "abstract": "The outcome of acute myelogenous leukemia (AML) therapy depends on the propensity of leukemic blasts to accumulate ara-CTP, the active triphosphate of cytarabine (ara-C). We identified sterile \u03b1 motif and HD domain-containing protein 1 (SAMHD1) as an ara-CTPase that protects cancer cells from cytarabine-induced toxicity. Therefore, we propose targeting SAMHD1 as a strategy to potentiate cytarabine and possibly other antimetabolite-based therapies.", "doi": "10.1080/23723556.2017.1287554", "pmid": "28401188", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC5383367"}, {"db": "pii", "key": "1287554"}], "notes": [], "created": "2026-08-20T09:37:44.566Z", "modified": "2026-08-20T09:37:44.676Z"}]}