{"entity": "researcher", "timestamp": "2026-10-13T19:02:49.875Z", "family": "Miller", "given": "Peter G", "initials": "PG", "orcid": "0000-0002-6797-9335", "affiliations": ["Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.", "Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/0abfb0f5d3fb419dbcfc03afa2885d41.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/0abfb0f5d3fb419dbcfc03afa2885d41"}}, "publications": [{"entity": "publication", "iuid": "7d942355294b4b20a4b2ab4bfe5c98ab", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/7d942355294b4b20a4b2ab4bfe5c98ab.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/7d942355294b4b20a4b2ab4bfe5c98ab"}}, "title": "SRCAP mutations drive clonal hematopoiesis through epigenetic and DNA repair dysregulation.", "authors": [{"family": "Chen", "given": "Chun-Wei", "initials": "CW"}, {"family": "Zhang", "given": "Linda", "initials": "L", "orcid": "0000-0001-9552-3848", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/92213aa004e349f09baf5440c791897e.json"}}, {"family": "Dutta", "given": "Ravi", "initials": "R"}, {"family": "Niroula", "given": "Abhishek", "initials": "A", "orcid": "0000-0002-5904-0635", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/05df7afc7a494ba5af8a378e5ffa53f0.json"}}, {"family": "Miller", "given": "Peter G", "initials": "PG", "orcid": "0000-0002-6797-9335", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0abfb0f5d3fb419dbcfc03afa2885d41.json"}}, {"family": "Gibson", "given": "Christopher J", "initials": "CJ", "orcid": "0000-0002-3700-5310", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/71ce9f64755e483496f8c28a76a2a1ff.json"}}, {"family": "Bick", "given": "Alexander G", "initials": "AG", "orcid": "0000-0001-5824-9595", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d2da5a35a4984921b19dfafe64cea2de.json"}}, {"family": "Reyes", "given": "Jaime M", "initials": "JM"}, {"family": "Lee", "given": "Yi-Tang", "initials": "YT"}, {"family": "Tovy", "given": "Ayala", "initials": "A"}, {"family": "Gu", "given": "Tianpeng", "initials": "T"}, {"family": "Waldvogel", "given": "Sarah", "initials": "S"}, {"family": "Chen", "given": "Yi-Hung", "initials": "YH"}, {"family": "Venters", "given": "Bryan J", "initials": "BJ"}, {"family": "Est\u00e8ve", "given": "Pierre-Olivier", "initials": "PO"}, {"family": "Pradhan", "given": "Sriharsa", "initials": "S"}, {"family": "Keogh", "given": "Michael-Christopher", "initials": "MC"}, {"family": "Natarajan", "given": "Pradeep", "initials": "P", "orcid": "0000-0001-8402-7435", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fe8bd48c61c047cd8e61c35d9e9ac650.json"}}, {"family": "Takahashi", "given": "Koichi", "initials": "K"}, {"family": "Sperling", "given": "Adam S", "initials": "AS", "orcid": "0000-0002-9369-4413", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b8fef41b72dd464f9f0e46ddcd0a2434.json"}}, {"family": "Goodell", "given": "Margaret A", "initials": "MA"}], "type": "journal article", "published": "2023-11-02", "journal": {"title": "Cell Stem Cell", "issn": "1875-9777", "volume": "30", "issue": "11", "pages": "1503-1519.e8", "issn-l": null}, "abstract": "Somatic mutations accumulate in all cells with age and can confer a selective advantage, leading to clonal expansion over time. In hematopoietic cells, mutations in a subset of genes regulating DNA repair or epigenetics frequently lead to clonal hematopoiesis (CH). Here, we describe the context and mechanisms that lead to enrichment of hematopoietic stem cells (HSCs) with mutations in SRCAP, which encodes a chromatin remodeler that also influences DNA repair. We show that SRCAP mutations confer a selective advantage in human cells and in mice upon treatment with the anthracycline-class chemotherapeutic doxorubicin and bone marrow transplantation. Furthermore, Srcap mutations lead to a lymphoid-biased expansion, driven by loss of SRCAP-regulated H2A.Z deposition and increased DNA repair. Altogether, we demonstrate that SRCAP operates at the intersection of multiple pathways in stem and progenitor cells, offering a new perspective on the functional impact of genetic variants that promote stem cell competition in the hematopoietic system.", "doi": "10.1016/j.stem.2023.09.011", "pmid": "37863054", "labels": {"Abhishek Niroula": null, "DDLS Fellow": null}, "xrefs": [{"db": "pii", "key": "S1934-5909(23)00358-2"}], "notes": [], "created": "2023-11-20T11:39:42.101Z", "modified": "2025-04-11T07:24:15.568Z"}, {"entity": "publication", "iuid": "2a03ef9ebe88444eb1262850a45b7daa", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2a03ef9ebe88444eb1262850a45b7daa.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2a03ef9ebe88444eb1262850a45b7daa"}}, "title": "TET2-mutant clonal hematopoiesis and risk of gout.", "authors": [{"family": "Agrawal", "given": "Mridul", "initials": "M"}, {"family": "Niroula", "given": "Abhishek", "initials": "A"}, {"family": "Cunin", "given": "Pierre", "initials": "P", "orcid": "0000-0001-8550-2306", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/363ef392810f4098843bf0c40ec53a0d.json"}}, {"family": "McConkey", "given": "Marie", "initials": "M"}, {"family": "Shkolnik", "given": "Veronica", "initials": "V"}, {"family": "Kim", "given": "Peter G", "initials": "PG"}, {"family": "Wong", "given": "Waihay J", "initials": "WJ", "orcid": "0000-0003-2023-6590", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3a4e1a5be5c54646ab5881bc338bf6cd.json"}}, {"family": "Weeks", "given": "Lachelle D", "initials": "LD", "orcid": "0000-0001-8726-6212", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ec1c3cd65e44fdb9f5cc2c2bf09bbc1.json"}}, {"family": "Lin", "given": "Amy E", "initials": "AE", "orcid": "0000-0002-0554-2832", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca94bff0b2bf49fda6fd77a16e6ef0fd.json"}}, {"family": "Miller", "given": "Peter G", "initials": "PG", "orcid": "0000-0002-6797-9335", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0abfb0f5d3fb419dbcfc03afa2885d41.json"}}, {"family": "Gibson", "given": "Christopher J", "initials": "CJ"}, {"family": "Sekar", "given": "Aswin", "initials": "A"}, {"family": "Schaefer", "given": "Inga-Marie", "initials": "IM", "orcid": "0000-0001-9710-5500", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8a87f32d6ccf4bfd8947b7ed9531aed7.json"}}, {"family": "Neuberg", "given": "Donna", "initials": "D"}, {"family": "Stone", "given": "Richard M", "initials": "RM"}, {"family": "Bick", "given": "Alexander G", "initials": "AG"}, {"family": "Uddin", "given": "Md Mesbah", "initials": "MM", "orcid": "0000-0003-1846-0411", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/42f1ac7010c34ba997a3fd9e56c6a56a.json"}}, {"family": "Griffin", "given": "Gabriel K", "initials": "GK"}, {"family": "Jaiswal", "given": "Siddhartha", "initials": "S", "orcid": "0000-0002-9597-0477", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a1901e08f989434fb01dfa17b0a85470.json"}}, {"family": "Natarajan", "given": "Pradeep", "initials": "P", "orcid": "0000-0001-8402-7435", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fe8bd48c61c047cd8e61c35d9e9ac650.json"}}, {"family": "Nigrovic", "given": "Peter A", "initials": "PA", "orcid": "0000-0002-2126-3702", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/06a54c6610794e30a29945f032c4c6bb.json"}}, {"family": "Rao", "given": "Deepak A", "initials": "DA", "orcid": "0000-0001-9672-7746", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/769f937bc2864984abc0718f548f6265.json"}}, {"family": "Ebert", "given": "Benjamin L", "initials": "BL", "orcid": "0000-0003-0197-5451", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/56e4f1c53a4348e2b0ceb44a38850a17.json"}}], "type": "journal article", "published": "2022-09-08", "journal": {"title": "Blood", "issn": "1528-0020", "volume": "140", "issue": "10", "pages": "1094-1103", "issn-l": "0006-4971"}, "abstract": "Gout is a common inflammatory arthritis caused by precipitation of monosodium urate (MSU) crystals in individuals with hyperuricemia. Acute flares are accompanied by secretion of proinflammatory cytokines, including interleukin-1\u03b2 (IL-1\u03b2). Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition predisposing to hematologic cancers and cardiovascular disease. CHIP is associated with elevated IL-1\u03b2, thus we investigated CHIP as a risk factor for gout. To test the clinical association between CHIP and gout, we analyzed whole exome sequencing data from 177 824 individuals in the MGB Biobank (MGBB) and UK Biobank (UKB). In both cohorts, the frequency of gout was higher among individuals with CHIP than without CHIP (MGBB, CHIP with variant allele fraction [VAF] \u22652%: odds ratio [OR], 1.69; 95% CI, 1.09-2.61; P = .0189; UKB, CHIP with VAF \u226510%: OR, 1.25; 95% CI, 1.05-1.50; P = .0133). Moreover, individuals with CHIP and a VAF \u226510% had an increased risk of incident gout (UKB: hazard ratio [HR], 1.28; 95% CI, 1.06-1.55; P = .0107). In murine models of gout pathogenesis, animals with Tet2 knockout hematopoietic cells had exaggerated IL-1\u03b2 secretion and paw edema upon administration of MSU crystals. Tet2 knockout macrophages elaborated higher levels of IL-1\u03b2 in response to MSU crystals in vitro, which was ameliorated through genetic and pharmacologic Nlrp3 inflammasome inhibition. These studies show that TET2-mutant CHIP is associated with an increased risk of gout in humans and that MSU crystals lead to elevated IL-1\u03b2 levels in Tet2 knockout murine models. We identify CHIP as an amplifier of NLRP3-dependent inflammatory responses to MSU crystals in patients with gout.", "doi": "10.1182/blood.2022015384", "pmid": "35714308", "labels": {"Abhishek Niroula": null, "DDLS Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC9461470"}, {"db": "pii", "key": "S0006-4971(22)00804-7"}], "notes": [], "created": "2023-11-20T11:36:20.793Z", "modified": "2023-11-20T11:36:21.146Z"}]}