{"entity": "researcher", "timestamp": "2026-03-10T03:03:57.460Z", "family": "R\u00fabies Bed\u00f3s", "given": "Marta", "initials": "M", "orcid": "0000-0003-0949-4329", "affiliations": ["Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/c25fafe4ed644a1890f9981b85c54e3d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/c25fafe4ed644a1890f9981b85c54e3d"}}, "publications": [{"entity": "publication", "iuid": "d07b869d108e479b83a9f4334d611e25", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/d07b869d108e479b83a9f4334d611e25.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/d07b869d108e479b83a9f4334d611e25"}}, "title": "Epigenetic regulation of cell state by H2AFY governs immunogenicity in high-risk neuroblastoma.", "authors": [{"family": "Nagarajan", "given": "Divya", "initials": "D"}, {"family": "Parracho", "given": "Rebeca T", "initials": "RT"}, {"family": "Corujo", "given": "David", "initials": "D"}, {"family": "Xie", "given": "Minglu", "initials": "M"}, {"family": "Kutkaite", "given": "Ginte", "initials": "G", "orcid": "0000-0002-2918-294X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/be0f080def0942e782116dca3d89c148.json"}}, {"family": "Olsen", "given": "Thale K", "initials": "TK"}, {"family": "R\u00fabies Bed\u00f3s", "given": "Marta", "initials": "M", "orcid": "0000-0003-0949-4329", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c25fafe4ed644a1890f9981b85c54e3d.json"}}, {"family": "Salehi", "given": "Maede", "initials": "M"}, {"family": "Baryawno", "given": "Ninib", "initials": "N"}, {"family": "Menden", "given": "Michael P", "initials": "MP", "orcid": "0000-0003-0267-5792", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/907d386ca4114274babf4703c976ecbe.json"}}, {"family": "Chen", "given": "Xingqi", "initials": "X", "orcid": "0000-0002-3214-9075", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4a7d95a9799a4c23bb01bf05fa6351cc.json"}}, {"family": "Buschbeck", "given": "Marcus", "initials": "M"}, {"family": "Mao", "given": "Yumeng", "initials": "Y", "orcid": "0000-0001-6142-6628", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ed7a1f5fdd354dad848c5f856d21d152.json"}}], "type": "journal article", "published": "2024-09-10", "journal": {"title": "J. Clin. Invest.", "issn": "1558-8238", "issn-l": "0021-9738"}, "abstract": "Childhood neuroblastoma with MYCN-amplification is classified as high-risk and often relapses after intensive treatments. Immune checkpoint blockade therapy against the PD-1/L1 axis shows limited efficacy in neuroblastoma patients and the cancer intrinsic immune regulatory network is poorly understood. Here, we leverage genome-wide CRISPR/Cas9 screens and identify H2AFY as a resistance gene to the clinically approved PD-1 blocking antibody, nivolumab. Analysis of single-cell RNA sequencing datasets reveals that H2AFY mRNA is enriched in adrenergic cancer cells and is associated with worse patient survival. Genetic deletion of H2afy in MYCN-driven neuroblastoma cells reverts in vivo resistance to PD-1 blockade by eliciting activation of the adaptive and innate immunity. Mapping of the epigenetic and translational landscape demonstrates that H2afy deletion promotes cell transition to a mesenchymal-like state. With a multi-omics approach, we uncover H2AFY-associated genes that are functionally relevant and prognostic in patients. Altogether, our study elucidates the role of H2AFY as an epigenetic gatekeeper for cell states and immunogenicity in high-risk neuroblastoma.", "doi": "10.1172/JCI175310", "pmid": "39255035", "labels": {"Yumeng Mao": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pii", "key": "175310"}], "notes": [], "created": "2024-10-29T15:43:38.571Z", "modified": "2025-04-07T06:59:54.593Z"}, {"entity": "publication", "iuid": "1b502acb3bd04917ac1f78622f207723", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1b502acb3bd04917ac1f78622f207723.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1b502acb3bd04917ac1f78622f207723"}}, "title": "Loss of NEDD8 in cancer cells causes vulnerability to immune checkpoint blockade in triple-negative breast cancer.", "authors": [{"family": "Papakyriacou", "given": "Irineos", "initials": "I"}, {"family": "Kutkaite", "given": "Ginte", "initials": "G", "orcid": "0000-0002-2918-294X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/be0f080def0942e782116dca3d89c148.json"}}, {"family": "R\u00fabies Bed\u00f3s", "given": "Marta", "initials": "M", "orcid": "0000-0003-0949-4329", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c25fafe4ed644a1890f9981b85c54e3d.json"}}, {"family": "Nagarajan", "given": "Divya", "initials": "D"}, {"family": "Alford", "given": "Liam P", "initials": "LP"}, {"family": "Menden", "given": "Michael P", "initials": "MP", "orcid": "0000-0003-0267-5792", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/907d386ca4114274babf4703c976ecbe.json"}}, {"family": "Mao", "given": "Yumeng", "initials": "Y", "orcid": "0000-0001-6142-6628", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ed7a1f5fdd354dad848c5f856d21d152.json"}}], "type": "journal article", "published": "2024-04-27", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "3581", "issn-l": "2041-1723"}, "abstract": "Immune checkpoint blockade therapy aims to activate the immune system to eliminate cancer cells. However, clinical benefits are only recorded in a subset of patients. Here, we leverage genome-wide CRISPR/Cas9 screens in a Tumor-Immune co-Culture System focusing on triple-negative breast cancer (TNBC). We reveal that NEDD8 loss in cancer cells causes a vulnerability to nivolumab (anti-PD-1). Genetic deletion of NEDD8 only delays cell division initially but cell proliferation is unaffected after recovery. Since the NEDD8 gene is commonly essential, we validate this observation with additional CRISPR screens and uncover enhanced immunogenicity in NEDD8 deficient cells using proteomics. In female immunocompetent mice, PD-1 blockade lacks efficacy against established EO771 breast cancer tumors. In contrast, we observe tumor regression mediated by CD8+ T cells against Nedd8 deficient EO771 tumors after PD-1 blockade. In essence, we provide evidence that NEDD8 is conditionally essential in TNBC and presents as a synergistic drug target for PD-1/L1 blockade therapy.", "doi": "10.1038/s41467-024-47987-x", "pmid": "38678024", "labels": {"Yumeng Mao": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC11055868"}, {"db": "pii", "key": "10.1038/s41467-024-47987-x"}], "notes": [], "created": "2024-10-29T15:43:39.808Z", "modified": "2024-10-29T15:43:40.342Z"}]}