{"entity": "researcher", "timestamp": "2026-08-20T20:53:17.063Z", "family": "Karsten", "given": "Stella", "initials": "S", "orcid": "0000-0001-6191-4314", "affiliations": ["Science for Life LaboratoryDepartment of Oncology and PathologyKarolinska InstitutetStockholmSweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/3a27ec21e4a34600aa24a7213372e19c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/3a27ec21e4a34600aa24a7213372e19c"}}, "publications": [{"entity": "publication", "iuid": "5c5bfa7eea964cf7961bdec3453b5d92", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5c5bfa7eea964cf7961bdec3453b5d92.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5c5bfa7eea964cf7961bdec3453b5d92"}}, "title": "Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function.", "authors": [{"family": "Michel", "given": "Maurice", "initials": "M", "orcid": "0000-0003-3261-2493", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f4696e361fe4aa3823d263674d1a498.json"}}, {"family": "Ben\u00edtez-Buelga", "given": "Carlos", "initials": "C"}, {"family": "Calvo", "given": "Patricia A", "initials": "PA"}, {"family": "Hanna", "given": "Bishoy M F", "initials": "BMF", "orcid": "0000-0001-7027-6553", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/61301102836e44d189f5628bb33c1335.json"}}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O", "orcid": "0000-0002-4290-4994", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f546fe8f2c54824b942f7f88976e3bd.json"}}, {"family": "Masuyer", "given": "Geoffrey", "initials": "G", "orcid": "0000-0002-9527-2310", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c62ba219d3e34662aaa458dbd361cf31.json"}}, {"family": "Davies", "given": "Jonathan", "initials": "J", "orcid": "0000-0002-4986-8594", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e74e0781a72d480c8e705a9a824e5e5a.json"}}, {"family": "Wallner", "given": "Olov", "initials": "O", "orcid": "0000-0002-6481-237X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3601a5a4d88f4452b6d1ac5f22c79d9f.json"}}, {"family": "Sanjiv", "given": "Kumar", "initials": "K", "orcid": "0000-0002-5415-9952", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f96227a0cfd8467ca6e8ac1146dda00a.json"}}, {"family": "Albers", "given": "Julian J", "initials": "JJ", "orcid": "0000-0001-9579-6360", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8278cc4e9e7e4bde823f672b1982591d.json"}}, {"family": "Casta\u00f1eda-Zegarra", "given": "Sergio", "initials": "S", "orcid": "0000-0002-2808-6788", "researcher": {"href": 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"0000-0003-4806-4233", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5c3ee8bcb2ee41f1982b48bfed84b76f.json"}}, {"family": "Rajagopal", "given": "Varshni", "initials": "V"}, {"family": "M\u00fcller", "given": "Sarah", "initials": "S", "orcid": "0000-0002-9923-3298", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5012b873ff66448eb2e0ae2e284f7b5b.json"}}, {"family": "Hank", "given": "Emily C", "initials": "EC", "orcid": "0000-0002-3777-4697", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2b412977f2364bef9ec63aa5e552331a.json"}}, {"family": "Varga", "given": "Marek", "initials": "M", "orcid": "0000-0002-9685-8145", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/707532fc225c49d1b2d4f9bec632e13f.json"}}, {"family": "Scaletti", "given": "Emma R", "initials": "ER", "orcid": "0000-0002-8741-8981", "researcher": {"href": 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"Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Henriksson", "given": "Martin", "initials": "M"}, {"family": "Michel", "given": "Dana", "initials": "D"}, {"family": "de Ory", "given": "Ana", "initials": "A"}, {"family": "Acero", "given": "Lucia", "initials": "L", "orcid": "0000-0001-8101-5412", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/af80832b8d8c4019bea17c15fa7651e2.json"}}, {"family": "Calvete", "given": "Oriol", "initials": "O", "orcid": "0000-0002-2623-2876", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0ee0251167344b24b97b971b8c750795.json"}}, {"family": "Scobie", "given": "Martin", "initials": "M", "orcid": "0000-0002-7073-8495", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bdce0df415d54e9d84a4fcbb4d1350e5.json"}}, {"family": "Hertweck", "given": "Christian", "initials": "C", "orcid": "0000-0002-0367-337X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2b1f3fa37a7d4378b06381c2e68a10cb.json"}}, {"family": "Vilotijevic", "given": "Ivan", "initials": "I", "orcid": "0000-0001-6199-0632", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/eec3fc0f230046ccbe7ff46b2da70792.json"}}, {"family": "Kalder\u00e9n", "given": "Christina", "initials": "C", "orcid": "0000-0001-7004-7048", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e9c7121a5e14414b8bace2708e8add2f.json"}}, {"family": "Osorio", "given": "Ana", "initials": "A", "orcid": "0000-0001-8124-3984", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6ecd4cc9c17d43009703efb95d979e09.json"}}, {"family": "Perona", "given": "Rosario", "initials": "R", "orcid": "0000-0002-2973-5153", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5b116837f5c346d49e70ad5eb28d7afb.json"}}, {"family": "Stolz", "given": "Alexandra", "initials": "A", "orcid": "0000-0002-3340-439X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4bde36f21953479a8762c1c858b4c451.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}, {"family": "Berglund", "given": "Ulrika Warpman", "initials": "UW", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8b6cab92fb2c4597a0c04777095f80db.json"}}, {"family": "de Vega", "given": "Miguel", "initials": "M", "orcid": "0000-0003-1285-7549", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6196fa790b4645c3acef45a87cdac3d0.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}], "type": "journal article", "published": "2022-06-24", "journal": {"title": "Science (New York, N.Y.)", "issn": "1095-9203", "volume": "376", "issue": "6600", "pages": "1471-1476", "issn-l": "0036-8075"}, "abstract": "Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed \u03b2,\u03b4-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging.", "doi": "10.1126/science.abf8980", "pmid": "35737787", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:59:29.051Z", "modified": "2026-08-20T11:59:30.134Z"}, {"entity": "publication", "iuid": "fd738e4f8a3840b1820a97c8deebf787", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/fd738e4f8a3840b1820a97c8deebf787.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/fd738e4f8a3840b1820a97c8deebf787"}}, "title": "MutT Homolog 1 Inhibitor Karonudib Attenuates Autoimmune Hepatitis by Inhibiting DNA Repair in Activated T Cells.", "authors": [{"family": "Chen", "given": "Yong", "initials": "Y"}, {"family": "Hua", "given": "Xiangwei", "initials": "X"}, {"family": "Huang", "given": "Bingyuan", "initials": "B"}, {"family": "Karsten", "given": "Stella", "initials": "S", "orcid": "0000-0001-6191-4314", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3a27ec21e4a34600aa24a7213372e19c.json"}}, {"family": "You", "given": "Zhengrui", "initials": "Z"}, {"family": "Li", "given": "Bo", "initials": "B"}, {"family": "Li", "given": "You", "initials": "Y"}, {"family": "Li", "given": "Yikang", "initials": "Y"}, {"family": "Liang", "given": "Jubo", "initials": "J"}, {"family": "Zhang", "given": "Jun", "initials": "J"}, {"family": "Wei", "given": "Yiran", "initials": "Y"}, {"family": "Chen", "given": "Ruiling", "initials": "R"}, {"family": "Lyu", "given": "Zhuwan", "initials": "Z", "orcid": "0000-0002-8437-8777", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/107db31746bf48cda42890aa3ef7b6ee.json"}}, {"family": "Xiao", "given": "Xiao", "initials": "X"}, {"family": "Lian", "given": "Min", "initials": "M"}, {"family": "Wei", "given": "Jue", "initials": "J"}, {"family": "Fang", "given": "Jingyuan", "initials": "J"}, {"family": "Miao", "given": "Qi", "initials": "Q"}, {"family": "Wang", "given": "Qixia", "initials": "Q"}, {"family": "Berglung", "given": "Ulrika Warpman", "initials": "UW"}, {"family": "Tang", "given": "Ruqi", "initials": "R"}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Ma", "given": "Xiong", "initials": "X", "orcid": "0000-0001-9616-4672", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b13d1a5dd21946fba0cbc41923315f01.json"}}], "type": "journal article", "published": "2022-05-00", "journal": {"title": "Hepatol Commun", "issn": "2471-254X", "volume": "6", "issue": "5", "pages": "1016-1031", "issn-l": null}, "abstract": "Autoimmune hepatitis (AIH) is an inflammatory liver disease driven by the hyperactivation of various intrahepatic antigen-specific T cells due to a breach of immune tolerance. Studies in immunometabolism demonstrate that activated T cells harbor increased levels of reactive oxygen species that cause oxidative DNA damage. In this study, we assessed the potential of DNA damage repair enzyme MutT homolog 1 (MTH1) as a therapeutic target in AIH and karonudib as a novel drug for patients with AIH. We report herein that MTH1 expression was significantly increased in liver samples from patients with AIH compared to patients with chronic hepatitis B and nonalcoholic fatty liver disease and from healthy controls. In addition, the expression of MTH1 was positively correlated with AIH disease severity. We further found abundant T cells that expressed MTH1 in AIH. Next, we found that karonudib significantly altered T-cell receptor signaling in human T cells and robustly inhibited proliferation of human T cells in vitro. Interestingly, our data reflected a preferential inhibition of DNA damage repair in activated T cells by karonudib. Moreover, MTH1 was required to develop liver inflammation and damage because specific deletion of MTH1 in T cells ameliorated liver injury in the concanavalin A (Con A)-induced hepatitis model by inhibiting T-cell activation and proliferation. Lastly, we validated the protective effect of karonudib on the Con A-induced hepatitis model. Conclusion: MTH1 functions as a critical regulator in the development of AIH, and its inhibition in activated T cells reduces liver inflammation and damage.", "doi": "10.1002/hep4.1862", "pmid": "34894107", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9035570"}, {"db": "pii", "key": "02009842-202205000-00008"}], "notes": [], "created": "2026-08-20T06:33:04.642Z", "modified": "2026-08-20T06:33:04.817Z"}, {"entity": "publication", "iuid": "bad6d71e7fb0452197c9d75414250a45", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/bad6d71e7fb0452197c9d75414250a45.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/bad6d71e7fb0452197c9d75414250a45"}}, "title": "MTH1 as a target to alleviate T cell driven diseases by selective suppression of activated T cells.", "authors": [{"family": "Karsten", "given": "Stella", "initials": "S", "orcid": "0000-0001-6191-4314", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3a27ec21e4a34600aa24a7213372e19c.json"}}, {"family": "Fiskesund", "given": "Roland", "initials": "R"}, {"family": "Zhang", "given": "Xing-Mei", "initials": "XM"}, {"family": "Marttila", "given": "Petra", "initials": "P", "orcid": "0000-0002-0115-8067", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ed95784f80a45d9abb072fbb74fc225.json"}}, {"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Pham", "given": "Therese", "initials": "T"}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "Br\u00e4utigam", "given": "Lars", "initials": "L"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Marcusson-St\u00e5hl", "given": "Maritha", "initials": "M"}, {"family": "Sandman", "given": "Carolina", "initials": "C"}, {"family": "Platzack", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Harris", "given": "Robert A", "initials": "RA"}, {"family": "Kalder\u00e9n", "given": "Christina", "initials": "C"}, {"family": "Cederbrant", "given": "Karin", "initials": "K"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U"}], "type": "journal article", "published": "2022-01-00", "journal": {"title": "Cell Death Differ.", "issn": "1476-5403", "volume": "29", "issue": "1", "pages": "246-261", "issn-l": "1350-9047"}, "abstract": "T cell-driven diseases account for considerable morbidity and disability globally and there is an urgent need for new targeted therapies. Both cancer cells and activated T cells have an altered redox balance, and up-regulate the DNA repair protein MTH1 that sanitizes the oxidized nucleotide pool to avoid DNA damage and cell death. Herein we suggest that the up-regulation of MTH1 in activated T cells correlates with their redox status, but occurs before the ROS levels increase, challenging the established conception of MTH1 increasing as a direct response to an increased ROS status. We also propose a heterogeneity in MTH1 levels among activated T cells, where a smaller subset of activated T cells does not up-regulate MTH1 despite activation and proliferation. The study suggests that the vast majority of activated T cells have high MTH1 levels and are sensitive to the MTH1 inhibitor TH1579 (Karonudib) via induction of DNA damage and cell cycle arrest. TH1579 further drives the surviving cells to the MTH1low phenotype with altered redox status. TH1579 does not affect resting T cells, as opposed to the established immunosuppressor Azathioprine, and no sensitivity among other major immune cell types regarding their function can be observed. Finally, we demonstrate a therapeutic effect in a murine model of experimental autoimmune encephalomyelitis. In conclusion, we show proof of concept of the existence of MTH1high and MTH1low activated T cells, and that MTH1 inhibition by TH1579 selectively suppresses pro-inflammatory activated T cells. Thus, MTH1 inhibition by TH1579 may serve as a novel treatment option against autoreactive T cells in autoimmune diseases, such as multiple sclerosis.", "doi": "10.1038/s41418-021-00854-4", "pmid": "34453118", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8738733"}, {"db": "pii", "key": "10.1038/s41418-021-00854-4"}], "notes": [], "created": "2026-08-20T08:49:19.589Z", "modified": "2026-08-20T08:49:19.664Z"}]}