{"entity": "researcher", "timestamp": "2026-08-20T21:11:24.261Z", "family": "Marttila", "given": "Petra", "initials": "P", "orcid": "0000-0002-0115-8067", "affiliations": ["Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ed95784f80a45d9abb072fbb74fc225.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ed95784f80a45d9abb072fbb74fc225"}}, "publications": [{"entity": "publication", "iuid": "05055972eaff415c8f51b09d91d400fd", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/05055972eaff415c8f51b09d91d400fd.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/05055972eaff415c8f51b09d91d400fd"}}, "title": "The one-carbon metabolic enzyme MTHFD2 promotes resection and homologous recombination after ionizing radiation.", "authors": [{"family": "Marttila", "given": "Petra", "initials": "P", "orcid": "0000-0002-0115-8067", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ed95784f80a45d9abb072fbb74fc225.json"}}, {"family": "Bonagas", "given": "Nadilly", "initials": "N"}, {"family": "Chalkiadaki", "given": "Christina", "initials": "C"}, {"family": "Stigsdotter", "given": "Hannah", "initials": "H"}, {"family": "Schelzig", "given": "Korbinian", "initials": "K", "orcid": "0009-0001-3791-0716", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a5ffa105eeea4750a28fd7b1f4b3e4de.json"}}, {"family": "Shen", "given": "Jianyu", "initials": "J"}, {"family": "Farhat", "given": "Crystal M", "initials": "CM"}, {"family": "Hondema", "given": "Amber", "initials": "A"}, {"family": "Albers", "given": "Julian", "initials": "J"}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U"}, {"family": "Slipicevic", "given": "Ana", "initials": "A"}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O", "orcid": "0000-0002-4290-4994", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f546fe8f2c54824b942f7f88976e3bd.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": "2024-09-00", "journal": {"title": "Mol Oncol", "issn": "1878-0261", "volume": "18", "issue": "9", "pages": "2179-2195", "issn-l": "1574-7891"}, "abstract": "The one-carbon metabolism enzyme bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2 (MTHFD2) is among the most overexpressed proteins across tumors and is widely recognized as a promising anticancer target. While MTHFD2 is mainly described as a mitochondrial protein, a new nuclear function is emerging. Here, we observe that nuclear MTHFD2 protein levels and association with chromatin increase following ionizing radiation (IR) in an ataxia telangiectasia mutated (ATM)- and DNA-dependent protein kinase (DNA-PK)-dependent manner. Furthermore, repair of IR-induced DNA double-strand breaks (DSBs) is delayed upon MTHFD2 knockdown, suggesting a role for MTHFD2 in DSB repair. In support of this, we observe impaired recruitment of replication protein A (RPA), reduced resection, decreased IR-induced DNA repair protein RAD51 homolog 1 (RAD51) levels and impaired homologous recombination (HR) activity in MTHFD2-depleted cells following IR. In conclusion, we identify a key role for MTHFD2 in HR repair and describe an interdependency between MTHFD2 and HR proficiency that could potentially be exploited for cancer therapy.", "doi": "10.1002/1878-0261.13645", "pmid": "38533616", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11467796"}], "notes": [], "created": "2026-08-20T06:26:58.460Z", "modified": "2026-08-20T06:26:58.641Z"}, {"entity": "publication", "iuid": "11bd337961b949c598f6d80b3c94b726", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/11bd337961b949c598f6d80b3c94b726.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/11bd337961b949c598f6d80b3c94b726"}}, "title": "Inhibition of MYC translation through targeting of the newly identified PHB-eIF4F complex as a therapeutic strategy in CLL.", "authors": [{"family": "Largeot", "given": "Anne", "initials": "A", "orcid": "0000-0002-9388-8461", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/828e7e2d26c348f6bc2a52a963150300.json"}}, {"family": "Klapp", "given": "Vanessa", "initials": "V", "orcid": "0000-0001-5507-1963", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8c5b05c01f4241f7a3e96cf9447541d8.json"}}, {"family": "Viry", "given": "Elodie", "initials": "E", "orcid": "0000-0002-1226-1473", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/189ea4ea0b744b78ad305245eedd2957.json"}}, {"family": "Gonder", "given": "Susanne", "initials": "S"}, {"family": "Fernandez Botana", "given": "Iria", "initials": "I"}, {"family": "Blomme", "given": "Arnaud", "initials": "A", "orcid": "0000-0003-4183-8726", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ea5a495fdcc416a828363efd6011d97.json"}}, {"family": "Benzarti", "given": "Mohaned", "initials": "M", "orcid": "0000-0002-6413-3983", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/29d514e15e394c2a83e27016a71b762e.json"}}, {"family": "Pierson", "given": "Sandrine", "initials": "S"}, {"family": "Duculty", "given": "Chlo\u00e9", "initials": "C", "orcid": "0000-0001-7643-0515", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/705000ddd8f04533b332afdfa94f98a0.json"}}, {"family": "Marttila", "given": "Petra", "initials": "P", "orcid": "0000-0002-0115-8067", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ed95784f80a45d9abb072fbb74fc225.json"}}, {"family": "Wierz", "given": "Marina", "initials": "M"}, {"family": "Gargiulo", "given": "Ernesto", "initials": "E", "orcid": "0000-0002-4485-4599", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3dacf1c644bf46a3a0df572b79f5c5dc.json"}}, {"family": "Pagano", "given": "Giulia", "initials": "G"}, {"family": "An", "given": "Ning", "initials": "N", "orcid": "0000-0001-9512-6869", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5848723ac56741f2b7ea9c5a20cf75b1.json"}}, {"family": "El Hachem", "given": "Najla", "initials": "N", "orcid": "0000-0002-4180-3016", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a0a80cc502e944089255a496ca0cc466.json"}}, {"family": "Perez Hernandez", "given": "Daniel", "initials": "D", "orcid": "0000-0003-0266-9050", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fa97441fb1c549d9ad8f44253edd3950.json"}}, {"family": "Chakraborty", "given": "Supriya", "initials": "S"}, {"family": "Ysebaert", "given": "Lo\u00efc", "initials": "L"}, {"family": "Fran\u00e7ois", "given": "Jean-Hugues", "initials": "JH"}, {"family": "Cortez Clemente", "given": "Susan", "initials": "S"}, {"family": "Berchem", "given": "Guy", "initials": "G", "orcid": "0000-0003-0157-2257", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e1cc8e55c1464d8b965f8f3fed6380d1.json"}}, {"family": "Efremov", "given": "Dimitar G", "initials": "DG"}, {"family": "Dittmar", "given": "Gunnar", "initials": "G", "orcid": "0000-0003-3647-8623", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9650701058af4aada77bc4792e54d70d.json"}}, {"family": "Szpakowska", "given": "Martyna", "initials": "M", "orcid": "0000-0002-5659-8377", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cadde97d7ad74f1eb4aa1c6f008fddba.json"}}, {"family": "Chevign\u00e9", "given": "Andy", "initials": "A", "orcid": "0000-0003-4768-6743", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d2f69f672fc6406a90dd2d764c5757b3.json"}}, {"family": "Nazarov", "given": "Petr V", "initials": "PV", "orcid": "0000-0003-3443-0298", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f772e1971f0f4917880b6cee31e9d8fa.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Close", "given": "Pierre", "initials": "P", "orcid": "0000-0002-8844-9616", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e6393d477030427385fadba415a672fe.json"}}, {"family": "Meiser", "given": "Johannes", "initials": "J", "orcid": "0000-0002-9093-6210", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/260ee7e5eb4a40589abc3f2966081083.json"}}, {"family": "Stamatopoulos", "given": "Basile", "initials": "B"}, {"family": "D\u00e9saubry", "given": "Laurent", "initials": "L", "orcid": "0000-0002-1192-2970", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/818f4308ee0643b3a9b74b7f9a65fdf9.json"}}, {"family": "Paggetti", "given": "J\u00e9r\u00f4me", "initials": "J", "orcid": "0000-0001-9460-5876", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a234b2f8d806420287ac79368e0d8165.json"}}, {"family": "Moussay", "given": "Etienne", "initials": "E", "orcid": "0000-0002-0879-8067", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cd5e599ae5344791b13409d09fdcef58.json"}}], "type": "journal article", "published": "2023-06-29", "journal": {"title": "Blood", "issn": "1528-0020", "volume": "141", "issue": "26", "pages": "3166-3183", "issn-l": "0006-4971"}, "abstract": "Dysregulation of messenger RNA (mRNA) translation, including preferential translation of mRNA with complex 5' untranslated regions such as the MYC oncogene, is recognized as an important mechanism in cancer. Here, we show that both human and murine chronic lymphocytic leukemia (CLL) cells display a high translation rate, which is inhibited by the synthetic flavagline FL3, a prohibitin (PHB)-binding drug. A multiomics analysis performed in samples from patients with CLL and cell lines treated with FL3 revealed the decreased translation of the MYC oncogene and of proteins involved in cell cycle and metabolism. Furthermore, inhibiting translation induced a proliferation arrest and a rewiring of MYC-driven metabolism. Interestingly, contrary to other models, the RAS-RAF-(PHBs)-MAPK pathway is neither impaired by FL3 nor implicated in translation regulation in CLL cells. Here, we rather show that PHBs are directly associated with the eukaryotic initiation factor (eIF)4F translation complex and are targeted by FL3. Knockdown of PHBs resembled FL3 treatment. Importantly, inhibition of translation controlled CLL development in vivo, either alone or combined with immunotherapy. Finally, high expression of translation initiation-related genes and PHBs genes correlated with poor survival and unfavorable clinical parameters in patients with CLL. Overall, we demonstrated that translation inhibition is a valuable strategy to control CLL development by blocking the translation of several oncogenic pathways including MYC. We also unraveled a new and direct role of PHBs in translation initiation, thus creating new therapeutic opportunities for patients with CLL.", "doi": "10.1182/blood.2022017839", "pmid": "37084385", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10646824"}, {"db": "pii", "key": "S0006-4971(23)00983-7"}], "notes": [], "created": "2026-08-20T12:17:59.415Z", "modified": "2026-08-20T12:18:00.233Z"}, {"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": "https://publications-affiliated.scilifelab.se/researcher/3438015dbc1d41b797a02c25a37fef60.json"}}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51f26d370fb74994b8e2b4fa1c9c2f7a.json"}}, {"family": "Visnes", "given": "Torkild", "initials": "T", "orcid": "0000-0003-1047-988X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9fef10d6a8604971a6ad1849b9f8b029.json"}}, {"family": "Sastre-Perona", "given": "Ana", "initials": "A", "orcid": "0000-0002-4502-3025", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7d1f1df32dbd449c8f10a5ce0872a6b3.json"}}, {"family": "Danda", "given": "Akhilesh N", "initials": "AN"}, {"family": "Homan", "given": "Evert J", "initials": "EJ", "orcid": "0000-0002-9057-1848", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3a68aa16414c4c159c52a5e75d5537c1.json"}}, {"family": "Marimuthu", "given": "Karthick", "initials": "K"}, {"family": "Zhenjun", "given": "Zhao", "initials": "Z", "orcid": "0000-0003-1976-0790", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/019926f6c3d649ea9b04b7b37956dfda.json"}}, {"family": "Chi", "given": "Celestine N", "initials": "CN"}, {"family": "Sarno", "given": "Antonio", "initials": "A", "orcid": "0000-0002-9308-8018", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/22883e442f534ba99f2917cf45d95b3d.json"}}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "von Nicolai", "given": "Catharina", "initials": "C", "orcid": "0000-0002-7116-2635", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b6a7ea3d84de4bcb9366c5dcb5b36779.json"}}, {"family": "Komor", "given": "Anna J", "initials": "AJ", "orcid": "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": "https://publications-affiliated.scilifelab.se/researcher/77be7f5d51564a75a753579e976c7c72.json"}}, {"family": "Pandey", "given": "Monica", "initials": "M", "orcid": "0000-0002-5783-5995", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1d5af32166634f20b29a5f1ed9e12c43.json"}}, {"family": "Karsten", "given": "Stella", "initials": "S", "orcid": "0000-0001-6191-4314", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3a27ec21e4a34600aa24a7213372e19c.json"}}, {"family": "Haslene-Hox", "given": "Hanne", "initials": "H"}, {"family": "Loevenich", "given": "Simon", "initials": "S", "orcid": "0000-0001-5424-8755", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6a06b60008414ef09b0c1e360ae1d10f.json"}}, {"family": "Marttila", "given": "Petra", "initials": "P", "orcid": "0000-0002-0115-8067", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ed95784f80a45d9abb072fbb74fc225.json"}}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "Mamonov", "given": "Kirill", "initials": "K", "orcid": "0000-0001-5971-4305", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2aeb36f9611f4c03883b8def30565da1.json"}}, {"family": "Ortis", "given": "Florian", "initials": "F", "orcid": "0000-0002-0458-5187", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a2e13b716bc349eb9dac083d7f801549.json"}}, {"family": "Sch\u00f6mberg", "given": "Fritz", "initials": "F", "orcid": "0000-0003-0092-0627", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7f10b06057e94d03a44967cce431c1a8.json"}}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Stewart", "given": "Josephine", "initials": "J"}, {"family": "D'Arcy-Evans", "given": "Nicholas", "initials": "N"}, {"family": "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": "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"}, {"entity": "publication", "iuid": "85dfc86719fd4e699a0a07008f7b0f67", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/85dfc86719fd4e699a0a07008f7b0f67.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/85dfc86719fd4e699a0a07008f7b0f67"}}, "title": "Crystal structures of human PAICS reveal substrate and product binding of an emerging cancer target.", "authors": [{"family": "\u0160kerlov\u00e1", "given": "Jana", "initials": "J", "orcid": "0000-0002-9579-4047", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2981680ce6de48ca84cfee5f74a94f27.json"}}, {"family": "Unterlass", "given": "Judith", "initials": "J"}, {"family": "G\u00f6ttmann", "given": "Mona", "initials": "M"}, {"family": "Marttila", "given": "Petra", "initials": "P", "orcid": "0000-0002-0115-8067", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ed95784f80a45d9abb072fbb74fc225.json"}}, {"family": "Homan", "given": "Evert", "initials": "E"}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51f26d370fb74994b8e2b4fa1c9c2f7a.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}], "type": "journal article", "published": "2020-08-14", "journal": {"title": "J Biol Chem", "issn": "1083-351X", "volume": "295", "issue": "33", "pages": "11656-11668", "issn-l": "0021-9258"}, "abstract": "The bifunctional human enzyme phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthetase (PAICS) catalyzes two essential steps in the de novo purine biosynthesis pathway. PAICS is overexpressed in many cancers and could be a promising target for the development of cancer therapeutics. Here, using gene knockdowns and clonogenic survival and cell viability assays, we demonstrate that PAICS is required for growth and survival of prostate cancer cells. PAICS catalyzes the carboxylation of aminoimidazole ribonucleotide (AIR) and the subsequent conversion of carboxyaminoimidazole ribonucleotide (CAIR) and l-aspartate to N-succinylcarboxamide-5-aminoimidazole ribonucleotide (SAICAR). Of note, we present the first structures of human octameric PAICS in complexes with native ligands. In particular, we report the structure of PAICS with CAIR bound in the active sites of both domains and SAICAR bound in one of the SAICAR synthetase domains. Moreover, we report the PAICS structure with SAICAR and an ATP analog occupying the SAICAR synthetase active site. These structures provide insight into substrate and product binding and the architecture of the active sites, disclosing important structural information for rational design of PAICS inhibitors as potential anticancer drugs.", "doi": "10.1074/jbc.RA120.013695", "pmid": "32571877", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7450103"}, {"db": "pii", "key": "S0021-9258(17)48465-1"}, {"db": "PDB", "key": "5clj"}, {"db": "PDB", "key": "2h31"}, {"db": "PDB", "key": "4ja0"}, {"db": "PDB", "key": "3rgg"}, {"db": "PDB", "key": "2nsl"}, {"db": "PDB", "key": "2gqs"}, {"db": "PDB", "key": "4fe2"}, {"db": "PDB", "key": "4o7w"}, {"db": "PDB", "key": "2z02"}, {"db": "PDB", "key": "2cnv"}, {"db": "PDB", "key": "2cnu"}, {"db": "PDB", "key": "1obd"}], "notes": [], "created": "2026-08-20T09:32:23.628Z", "modified": "2026-08-20T09:32:23.752Z"}]}