{"entity": "researcher", "timestamp": "2026-08-26T23:12:11.495Z", "family": "Gursky", "given": "J", "initials": "J", "orcid": "0000-0002-5761-7066", "affiliations": ["Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/e6c2eb2724144401b00a5b0c21fbfa38.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/e6c2eb2724144401b00a5b0c21fbfa38"}}, "publications": [{"entity": "publication", "iuid": "e76fe6005a4849ed99b9e64b55342a2d", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e76fe6005a4849ed99b9e64b55342a2d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e76fe6005a4849ed99b9e64b55342a2d"}}, "title": "Disulfiram's anti-cancer activity reflects targeting NPL4, not inhibition of aldehyde dehydrogenase.", "authors": [{"family": "Skrott", "given": "Zdenek", "initials": "Z"}, {"family": "Majera", "given": "Dusana", "initials": "D"}, {"family": "Gursky", "given": "Jan", "initials": "J", "orcid": "0000-0002-5761-7066", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e6c2eb2724144401b00a5b0c21fbfa38.json"}}, {"family": "Buchtova", "given": "Tereza", "initials": "T"}, {"family": "Hajduch", "given": "Marian", "initials": "M", "orcid": "0000-0002-4834-908X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fc2ce16232a24979a6e2a18b154fbc13.json"}}, {"family": "Mistrik", "given": "Martin", "initials": "M"}, {"family": "Bartek", "given": "Jiri", "initials": "J"}], "type": "journal article", "published": "2019-10-00", "journal": {"title": "Oncogene", "issn": "1476-5594", "volume": "38", "issue": "40", "pages": "6711-6722", "issn-l": "0950-9232"}, "abstract": "Aldehyde dehydrogenase (ALDH) is a proposed biomarker and possible target to eradicate cancer stem cells. ALDH inhibition as a treatment approach is supported by anti-cancer effects of the alcohol-abuse drug disulfiram (DSF, Antabuse). Given that metabolic products of DSF, rather than DSF itself inhibit ALDH in vivo, and that DSF's anti-cancer activity is potentiated by copper led us to investigate the relevance of ALDH as the suggested molecular cancer-relevant target of DSF. Here we show that DSF does not directly inhibit ALDH activity in diverse human cell types, while DSF's in vivo metabolite, S-methyl-N,N-diethylthiocarbamate-sulfoxide inhibits ALDH activity yet does not impair cancer cell viability. Our data indicate that the anti-cancer activity of DSF does not involve ALDH inhibition, and rather reflects the impact of DSF's copper-containing metabolite (CuET), that forms spontaneously in vivo and in cell culture media, and kills cells through aggregation of NPL4, a subunit of the p97/VCP segregase. We also show that the CuET-mediated, rather than any ALDH-inhibitory activity of DSF underlies the preferential cytotoxicity of DSF towards BRCA1- and BRCA2-deficient cells. These findings provide evidence clarifying the confusing literature about the anti-cancer mechanism of DSF, a drug currently tested in clinical trials for repositioning in oncology.", "doi": "10.1038/s41388-019-0915-2", "pmid": "31391554", "labels": [], "xrefs": [{"db": "pii", "key": "10.1038/s41388-019-0915-2"}], "notes": [], "created": "2026-08-20T08:48:17.365Z", "modified": "2026-08-20T08:48:17.462Z"}, {"entity": "publication", "iuid": "1bf7084a70bd4d28b96b43088ce659e7", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1bf7084a70bd4d28b96b43088ce659e7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1bf7084a70bd4d28b96b43088ce659e7"}}, "title": "Addiction to DUSP1 protects JAK2V617F-driven polycythemia vera progenitors against inflammatory stress and DNA damage, allowing chronic proliferation.", "authors": [{"family": "Stetka", "given": "J", "initials": "J", "orcid": "0000-0003-4301-2856", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ef1e30ff8c9f47efa1bf5e4454281b90.json"}}, {"family": "Vyhlidalova", "given": "P", "initials": "P", "orcid": "0000-0002-2522-6749", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6e6c2c42653c418bb27a01e32fbe9eb4.json"}}, {"family": "Lanikova", "given": "L", "initials": "L"}, {"family": "Koralkova", "given": "P", "initials": "P"}, {"family": "Gursky", "given": "J", "initials": "J", "orcid": "0000-0002-5761-7066", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e6c2eb2724144401b00a5b0c21fbfa38.json"}}, {"family": "Hlusi", "given": "A", "initials": "A"}, {"family": "Flodr", "given": "P", "initials": "P"}, {"family": "Hubackova", "given": "S", "initials": "S"}, {"family": "Bartek", "given": "J", "initials": "J"}, {"family": "Hodny", "given": "Z", "initials": "Z"}, {"family": "Divoky", "given": "V", "initials": "V"}], "type": "journal article", "published": "2019-07-00", "journal": {"title": "Oncogene", "issn": "1476-5594", "volume": "38", "issue": "28", "pages": "5627-5642", "issn-l": "0950-9232"}, "abstract": "Inflammatory and oncogenic signaling converge in disease evolution of BCR-ABL-negative myeloproliferative neoplasms, clonal hematopoietic stem cell disorders characterized by gain-of-function mutation in JAK2 kinase (JAK2V617F), with highest prevalence in patients with polycythemia vera (PV). Despite the high risk, DNA-damaging inflammatory microenvironment, PV progenitors tend to preserve their genomic stability over decades until their progression to post-PV myelofibrosis/acute myeloid leukemia. Using induced pluripotent stem cells-derived CD34+ progenitor-enriched cultures from JAK2V617F+ PV patient and from JAK2 wild-type healthy control, CRISPR-modified HEL cells and patients' bone marrow sections from different disease stages, we demonstrate that JAK2V617F induces an intrinsic IFN\u03b3- and NF-\u03baB-associated inflammatory program, while suppressing inflammation-evoked DNA damage both in vitro and in vivo. We show that cells with JAK2V617F tightly regulate levels of inflammatory cytokines-induced reactive oxygen species, do not fully activate the ATM/p53/p21waf1 checkpoint and p38/JNK MAPK stress pathway signaling when exposed to inflammatory cytokines, suppress DNA single-strand break repair genes' expression yet overexpress the dual-specificity phosphatase (DUSP) 1. RNAi-mediated knock-down and pharmacological inhibition of DUSP1, involved in p38/JNK deactivation, in HEL cells reveals growth addiction to DUSP1, consistent with enhanced DNA damage response and apoptosis in DUSP1-inhibited parental JAK2V617F+ cells, but not in CRISPR-modified JAK2 wild-type cells. Our results indicate that the JAK2V617F+ PV progenitors utilize DUSP1 activity as a protection mechanism against DNA damage accumulation, promoting their proliferation and survival in the inflammatory microenvironment, identifying DUSP1 as a potential therapeutic target in PV.", "doi": "10.1038/s41388-019-0813-7", "pmid": "30967632", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6756199"}, {"db": "pii", "key": "10.1038/s41388-019-0813-7"}], "notes": [], "created": "2026-08-20T08:48:15.442Z", "modified": "2026-08-20T08:48:15.631Z"}]}