{"entity": "researcher", "timestamp": "2026-09-25T23:39:49.492Z", "family": "Onireti", "given": "Jacob", "initials": "J", "orcid": "0009-0003-9745-4446", "affiliations": ["Science for Life Laboratory, Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, SE-141 52, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/074e191bf6424acd85df1a249e8b3c6c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/074e191bf6424acd85df1a249e8b3c6c"}}, "publications": [{"entity": "publication", "iuid": "1beeb04989624be796da0f09ff3788d8", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1beeb04989624be796da0f09ff3788d8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1beeb04989624be796da0f09ff3788d8"}}, "title": "Coupling cellular drug-target engagement to downstream pharmacology with CeTEAM.", "authors": [{"family": "Valerie", "given": "Nicholas C K", "initials": "NCK", "orcid": "0000-0002-9423-964X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/48bb9c8ab8a5465a8a4da1997f1af56d.json"}}, {"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O", "orcid": "0000-0002-4290-4994", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f546fe8f2c54824b942f7f88976e3bd.json"}}, {"family": "Zhang", "given": "Si Min", "initials": "SM", "orcid": "0000-0001-7763-603X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/755a7ac0bd8c4e869428927871cead93.json"}}, {"family": "Alam", "given": "Seher", "initials": "S"}, {"family": "Pires", "given": "Maria J", "initials": "MJ"}, {"family": "Stigsdotter", "given": "Hannah", "initials": "H"}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "Langelier", "given": "Marie-France", "initials": "MF", "orcid": "0000-0001-9815-1840", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/79beb7ce9d3b46528f35b1cf9038cf65.json"}}, {"family": "Rehling", "given": "Daniel", "initials": "D"}, {"family": "Throup", "given": "Adam", "initials": "A", "orcid": "0000-0001-6512-8679", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1d7373aaa685464492b615ea4152b843.json"}}, {"family": "Purewal-Sidhu", "given": "Oryn", "initials": "O"}, {"family": "Desroses", "given": "Matthieu", "initials": "M"}, {"family": "Onireti", "given": "Jacob", "initials": "J", "orcid": "0009-0003-9745-4446", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/074e191bf6424acd85df1a249e8b3c6c.json"}}, {"family": "Wakchaure", "given": "Prasad", "initials": "P"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Bostr\u00f6m", "given": "Johan", "initials": "J"}, {"family": "Bevc", "given": "Luka", "initials": "L"}, {"family": "Benzi", "given": "Giorgia", "initials": "G"}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}, {"family": "Pascal", "given": "John M", "initials": "JM", "orcid": "0000-0002-2714-4317", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/82a900bd9df84da594641911c65750f1.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}, {"family": "Page", "given": "Brent D G", "initials": "BDG"}, {"family": "Altun", "given": "Mikael", "initials": "M", "orcid": "0000-0002-6937-6124", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d77b74fe6e7d44f4800fe8bb4404ad8f.json"}}], "type": "journal article", "published": "2024-12-06", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "10347", "issn-l": "2041-1723"}, "abstract": "Cellular target engagement technologies enable quantification of intracellular drug binding; however, simultaneous assessment of drug-associated phenotypes has proven challenging. Here, we present cellular target engagement by accumulation of mutant as a platform that can concomitantly evaluate drug-target interactions and phenotypic responses using conditionally stabilized drug biosensors. We observe that drug-responsive proteotypes are prevalent among reported mutants of known drug targets. Compatible mutants appear to follow structural and biophysical logic that permits intra-protein and paralogous expansion of the biosensor pool. We then apply our method to uncouple target engagement from divergent cellular activities of MutT homolog 1 (MTH1) inhibitors, dissect Nudix hydrolase 15 (NUDT15)-associated thiopurine metabolism with the R139C pharmacogenetic variant, and profile the dynamics of poly(ADP-ribose) polymerase 1/2 (PARP1/2) binding and DNA trapping by PARP inhibitors (PARPi). Further, PARP1-derived biosensors facilitated high-throughput screening for PARP1 binders, as well as multimodal ex vivo analysis and non-invasive tracking of PARPi binding in live animals. This approach can facilitate holistic assessment of drug-target engagement by bridging drug binding events and their biological consequences.", "doi": "10.1038/s41467-024-54415-7", "pmid": "39643609", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11624193"}, {"db": "pii", "key": "10.1038/s41467-024-54415-7"}], "notes": [], "created": "2026-09-23T11:32:00.387Z", "modified": "2026-09-23T11:32:00.579Z"}]}