{"entity": "researcher", "timestamp": "2026-07-20T12:27:01.388Z", "family": "Treis", "given": "Diana", "initials": "D", "orcid": "0000-0002-7887-9436", "affiliations": ["Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, and Pediatric Oncology, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden"], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/c4ba612265714e60adca9d33db4bed9f.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/c4ba612265714e60adca9d33db4bed9f"}}, "publications": [{"entity": "publication", "iuid": "f9e0fcd794fd47fe9f5bb17cd10c2f79", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f9e0fcd794fd47fe9f5bb17cd10c2f79.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f9e0fcd794fd47fe9f5bb17cd10c2f79"}}, "title": "Targeted inhibition of WIP1 and histone H3K27 demethylase activity synergistically suppresses neuroblastoma growth.", "authors": [{"family": "Treis", "given": "Diana", "initials": "D", "orcid": "0000-0002-7887-9436", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4ba612265714e60adca9d33db4bed9f.json"}}, {"family": "Lundberg", "given": "Kristina Ihrmark", "initials": "KI"}, {"family": "Bell", "given": "Nicola", "initials": "N"}, {"family": "Polychronopoulos", "given": "Panagiotis Alkinoos", "initials": "PA"}, {"family": "T\u00fcmmler", "given": "Conny", "initials": "C", "orcid": "0000-0002-5530-4752", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a938c192b2d42a89ac210024bfab7a5.json"}}, {"family": "\u00c5kerlund", "given": "Emma", "initials": "E"}, {"family": "Aliverti", "given": "Stefania", "initials": "S"}, {"family": "Lilienthal", "given": "Ingrid", "initials": "I"}, {"family": "Pepich", "given": "Adena", "initials": "A"}, {"family": "Seashore-Ludlow", "given": "Brinton", "initials": "B", "orcid": "0000-0001-8658-5967", "researcher": {"href": "https://publications.scilifelab.se/researcher/4645bc97a8024c548111802101b83571.json"}}, {"family": "Sakaguchi", "given": "Kazuyasu", "initials": "K", "orcid": "0000-0002-8434-4171", "researcher": {"href": "https://publications.scilifelab.se/researcher/9ce1a573aec14041873a5a5700c224c9.json"}}, {"family": "Kogner", "given": "Per", "initials": "P", "orcid": "0000-0002-2202-9694", "researcher": {"href": "https://publications.scilifelab.se/researcher/e963274b921a4a2c8263f509334d4e22.json"}}, {"family": "Johnsen", "given": "John Inge", "initials": "JI", "orcid": "0000-0003-1277-812X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c5b7b4c780349afacf3063e311c334e.json"}}, {"family": "Wickstr\u00f6m", "given": "Malin", "initials": "M", "orcid": "0000-0001-5214-9956", "researcher": {"href": "https://publications.scilifelab.se/researcher/2bd8b895bc0a4dca89c4170f85d3ebb4.json"}}], "type": "journal article", "published": "2025-04-19", "journal": {"title": "Cell Death Dis", "issn": "2041-4889", "volume": "16", "issue": "1", "pages": "318", "issn-l": "2041-4889"}, "abstract": "High-risk neuroblastoma frequently exhibits segmental gain of chromosome 17q, including the locus of PPM1D, which encodes the phosphatase WIP1, a regulator of p53 activity, DNA repair, and apoptosis. High expression of PPM1D is correlated to poor prognosis, and genetic or pharmacologic inhibition of WIP1 suppresses neuroblastoma growth. Here, we show that combining drugs that target WIP1 and H3K27 demethylation induces synergistic cytotoxicity in neuroblastoma. We screened 527 different compounds together with inhibitors of WIP1 and identified a strong cytotoxic synergism between the WIP1 inhibitor SL-176 and GSK-J4, a specific inhibitor of the H3K27 demethylase JMJD3. Viability assays in neuroblastoma cell lines and treatment of tumor spheroids confirmed the synergistic effect of combining SL-176 with GSK-J4. Immunoblot experiments demonstrated a marked effect on WIP1 downstream targets and apoptosis markers, while qPCR showed a synergistic upregulation of p53 downstream targets PUMA and p21. RNA sequencing revealed a vast number of differentially expressed genes, suggesting a pervasive effect of this drug combination on transcription, with enrichment of pathways involved in DNA damage response. Finally, this drug combination was confirmed to reduce tumor growth in zebrafish xenograft experiments. In conclusion, the combination of the WIP1 inhibitor SL-176 and the epigenetic modifier GSK-J4 induces synergistic cytotoxicity in neuroblastoma cells by potentiating p53 downstream effects.", "doi": "10.1038/s41419-025-07658-1", "pmid": "40253363", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12009370"}, {"db": "pii", "key": "10.1038/s41419-025-07658-1"}], "notes": [], "created": "2025-11-28T10:45:07.721Z", "modified": "2025-11-28T10:45:08.055Z"}, {"entity": "publication", "iuid": "5777a937f5bc4433bd4fc6efc8aec0a0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5777a937f5bc4433bd4fc6efc8aec0a0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5777a937f5bc4433bd4fc6efc8aec0a0"}}, "title": "Multifocal Neuroblastoma and Central Hypoventilation in An Infant with Germline ALK F1174I Mutation.", "authors": [{"family": "Djos", "given": "Anna", "initials": "A", "orcid": "0000-0002-5250-2163", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f5b7b38c97d484cabc7013354b16fb5.json"}}, {"family": "Treis", "given": "Diana", "initials": "D", "orcid": "0000-0002-7887-9436", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4ba612265714e60adca9d33db4bed9f.json"}}, {"family": "Fransson", "given": "Susanne", "initials": "S", "orcid": "0000-0002-9713-3074", "researcher": {"href": "https://publications.scilifelab.se/researcher/e3f155163dae47478aae39b9c47fdadc.json"}}, {"family": "Gordon Murkes", "given": "Lena", "initials": "L"}, {"family": "Wessman", "given": "Sandra", "initials": "S", "orcid": "0000-0002-2035-2092", "researcher": {"href": "https://publications.scilifelab.se/researcher/f4680125750b4d949d691a745818a6f7.json"}}, {"family": "\u00c1smundsson", "given": "Jurate", "initials": "J", "orcid": "0000-0001-9104-9413", "researcher": {"href": "https://publications.scilifelab.se/researcher/6c2eba1eb8974c6caaf0e0a9680edfa3.json"}}, {"family": "Markstr\u00f6m", "given": "Agneta", "initials": "A"}, {"family": "Kogner", "given": "Per", "initials": "P", "orcid": "0000-0002-2202-9694", "researcher": {"href": "https://publications.scilifelab.se/researcher/e963274b921a4a2c8263f509334d4e22.json"}}, {"family": "Martinsson", "given": "Tommy", "initials": "T", "orcid": "0000-0002-9403-3123", "researcher": {"href": "https://publications.scilifelab.se/researcher/90deb3f5dd5446e5853da797411dfd5d.json"}}], "type": "case reports", "published": "2022-09-19", "journal": {"title": "Diagnostics", "issn": "2075-4418", "issn-l": "2075-4418", "volume": "12", "issue": "9", "pages": null}, "abstract": "A preterm infant with central hypoventilation was diagnosed with multifocal neuroblastoma. Congenital anomalies of the autonomic nervous system in association with neuroblastoma are commonly associated with germline mutations in PHOX2B. Further, the ALK gene is frequently mutated in both familial and sporadic neuroblastoma. Sanger sequencing of ALK and PHOX2B, SNP microarray of three tumor samples and whole genome sequencing of tumor and blood were performed. Genetic testing revealed a germline ALK F1174I mutation that was present in all tumor samples as well as in normal tissue samples from the patient. Neither of the patient's parents presented the ALK variant. Array profiling of the three tumor samples showed that two of them had only numerical aberrations, whereas one sample displayed segmental alterations, including a gain at chromosome 2p, resulting in two copies of the ALK-mutated allele. Whole genome sequencing confirmed the presence of the ALK variant and did not detect any aberrations in the coding or promotor region of PHOX2B. This study is to our knowledge the first to report a de novoALK F1174I germline mutation. This may not only predispose to congenital multifocal neuroblastoma but may also contribute to the respiratory dysfunction seen in this patient.", "doi": "10.3390/diagnostics12092260", "pmid": "36140661", "labels": {"Clinical Genomics Gothenburg": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9498070"}, {"db": "pii", "key": "diagnostics12092260"}], "notes": [], "created": "2022-12-02T12:22:39.427Z", "modified": "2024-01-16T13:48:34.997Z"}, {"entity": "publication", "iuid": "bde930e1ab6a48cba150fbe29c2900b2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bde930e1ab6a48cba150fbe29c2900b2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bde930e1ab6a48cba150fbe29c2900b2"}}, "title": "Sustained Response to Entrectinib in an Infant With a Germline ALKAL2 Variant and Refractory Metastatic Neuroblastoma With Chromosomal 2p Gain and Anaplastic Lymphoma Kinase and Tropomyosin Receptor Kinase Activation.", "authors": [{"family": "Treis", "given": "Diana", "initials": "D", "orcid": "0000-0002-7887-9436", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4ba612265714e60adca9d33db4bed9f.json"}}, {"family": "Umapathy", "given": "Ganesh", "initials": "G", "orcid": "0000-0003-2324-8300", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc307910309d481f8a5c5446fce4ef60.json"}}, {"family": "Fransson", "given": "Susanne", "initials": "S", "orcid": "0000-0002-9713-3074", "researcher": {"href": "https://publications.scilifelab.se/researcher/e3f155163dae47478aae39b9c47fdadc.json"}}, {"family": "Guan", "given": "Jikui", "initials": "J", "orcid": "0000-0003-1723-0307", "researcher": {"href": "https://publications.scilifelab.se/researcher/a39044157aa7475485fb489a003b63d1.json"}}, {"family": "Mendoza-Garc\u00eda", "given": "Patricia", "initials": "P", "orcid": "0000-0002-6084-7962", "researcher": {"href": "https://publications.scilifelab.se/researcher/52b479a94b9e4406aada9911c0505268.json"}}, {"family": "Siaw", "given": "Joachim T", "initials": "JT", "orcid": "0000-0002-1286-4485", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a4ce00b5a4b4ebb9ee746de59e2e943.json"}}, {"family": "Wessman", "given": "Sandra", "initials": "S"}, {"family": "Gordon Murkes", "given": "Lena", "initials": "L"}, {"family": "Stenman", "given": "Jakob J E", "initials": "JJE"}, {"family": "Djos", "given": "Anna", "initials": "A", "orcid": "0000-0002-5250-2163", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f5b7b38c97d484cabc7013354b16fb5.json"}}, {"family": "Elfman", "given": "Lotta H M", "initials": "LHM"}, {"family": "Johnsen", "given": "John Inge", "initials": "JI"}, {"family": "Hallberg", "given": "Bengt", "initials": "B"}, {"family": "Palmer", "given": "Ruth H", "initials": "RH", "orcid": "0000-0002-2735-8470", "researcher": {"href": "https://publications.scilifelab.se/researcher/808281ecc2634b66a274895e58a122bd.json"}}, {"family": "Martinsson", "given": "Tommy", "initials": "T", "orcid": "0000-0002-9403-3123", "researcher": {"href": "https://publications.scilifelab.se/researcher/90deb3f5dd5446e5853da797411dfd5d.json"}}, {"family": "Kogner", "given": "Per", "initials": "P", "orcid": "0000-0002-2202-9694", "researcher": {"href": "https://publications.scilifelab.se/researcher/e963274b921a4a2c8263f509334d4e22.json"}}], "type": "case reports", "published": "2022-01-00", "journal": {"title": "JCO Precision Oncology", "issn": "2473-4284", "issue": "6", "volume": "6", "pages": "e2100271", "issn-l": "2473-4284"}, "abstract": null, "doi": "10.1200/PO.21.00271", "pmid": "35085006", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics Gothenburg": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8830523"}], "notes": [], "created": "2022-02-13T16:40:34.583Z", "modified": "2022-12-02T12:22:28.986Z"}]}