{"entity": "label", "iuid": "da337992ca7b4bbfa35362d4ce4ed882", "timestamp": "2026-06-15T20:29:51.187Z", "links": {"self": {"href": "https://publications.scilifelab.se/label/Chemical%20Proteomics.json"}, "display": {"href": "https://publications.scilifelab.se/label/Chemical%20Proteomics"}}, "value": "Chemical Proteomics", "started": "2017", "ended": "", "created": "2020-01-20T13:33:09.869Z", "modified": "2021-03-15T14:15:56.260Z", "accounts": [{"entity": "account", "iuid": "2d21da4c779242ea801344e3ae973871", "timestamp": "2026-06-15T20:29:51.187Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/massimiliano.gaetani%40ki.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/massimiliano.gaetani%40ki.se"}}, "email": "massimiliano.gaetani@ki.se", "name": "Massimiliano Gaetani", "orcid": null, "role": "curator", "status": "enabled", "login": "2026-05-25T19:00:36.982Z", "created": "2017-10-04T13:37:34.475Z", "modified": "2026-05-25T19:00:36.982Z"}, {"entity": "account", "iuid": "32a436398938412b93e7ddcef018c708", "timestamp": "2026-06-15T20:29:51.187Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/christopher.erdmann%40scilifelab.uu.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/christopher.erdmann%40scilifelab.uu.se"}}, "email": "christopher.erdmann@scilifelab.uu.se", "name": "Christopher Erdmann", "orcid": "", "role": "curator", "status": "enabled", "login": "2024-08-16T11:56:57.787Z", "created": "2024-08-16T10:01:32.844Z", "modified": "2025-10-17T13:05:06.782Z"}, {"entity": "account", "iuid": "6a38350bd21f4fb6aeeb1530037a99ae", "timestamp": "2026-06-15T20:29:51.187Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/sune.joubert%40scilifelab.uu.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/sune.joubert%40scilifelab.uu.se"}}, "email": "sune.joubert@scilifelab.uu.se", "name": "Sun\u00e9 Joubert", "orcid": "", "role": "curator", "status": "enabled", "login": "2025-10-31T11:15:37.113Z", "created": "2024-08-16T10:01:02.800Z", "modified": "2025-10-31T11:15:37.113Z"}], "publications_count": 53, "publications": [{"entity": "publication", "iuid": "4a7100c23e144b7abdf8d58ddb80b6c6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4a7100c23e144b7abdf8d58ddb80b6c6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4a7100c23e144b7abdf8d58ddb80b6c6"}}, "title": "Above-Filter Digestion Proteomics Reveals Drug Targets and Localizes Ligand Binding Site.", "authors": [{"family": "Sokolova", "given": "Bohdana", "initials": "B", "orcid": "0000-0003-3751-7129", "researcher": {"href": "https://publications.scilifelab.se/researcher/6276043c6670459785d175983f625167.json"}}, {"family": "Gharibi", "given": "Hassan", "initials": "H", "orcid": "0000-0002-3072-4929", "researcher": {"href": "https://publications.scilifelab.se/researcher/b85179acfa7e4916ad40ae478d6dcc0a.json"}}, {"family": "Jafari", "given": "Maryam", "initials": "M"}, {"family": "Lyu", "given": "Hezheng", "initials": "H"}, {"family": "Lovera", "given": "Silvia", "initials": "S"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Saei", "given": "Amir Ata", "initials": "AA"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "journal article", "published": "2026-03-06", "journal": {"title": "J. Proteome Res.", "issn": "1535-3907", "volume": "25", "issue": "3", "pages": "1556-1570", "issn-l": "1535-3893"}, "abstract": "Identifying how drugs interact with proteins is fundamental to understanding their therapeutic effects and side effects. While numerous chemical proteomics methods exist for determining protein targets of drugs, each exhibits \"blind spots,\" necessitating complementary approaches. We introduce Above-Filter Digestion Proteomics (AFDIP), which monitors trypsin digestion rates that decrease at ligand-binding sites, while potentially increasing elsewhere. Molecular dynamics simulations showed that these changes relate to backbone flexibility. Using AFDIP, we identified targets of various drugs and metabolites, allowing two-dimensional analysis with the drug concentration as the second dimension. The method identifies binding sites within \u226410 \u00c5 of crystallography-determined locations with improved resolution (\u22645 \u00c5) for larger proteins. Compared with existing proteolysis approaches, AFDIP offers simpler sample preparation, deeper proteome analysis, and broader sequence coverage. AFDIP addresses the blind spots of current techniques and provides structural insights, enhancing the chemical proteomics toolkit.", "doi": "10.1021/acs.jproteome.5c00927", "pmid": "41653152", "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC12973292"}], "notes": [], "created": "2026-05-25T19:27:19.747Z", "modified": "2026-05-25T19:27:20.312Z"}, {"entity": "publication", "iuid": "c3f74b41f9be44d2ba332d6d5c86782a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c3f74b41f9be44d2ba332d6d5c86782a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c3f74b41f9be44d2ba332d6d5c86782a"}}, "title": "Copper ionophore elicits calpain-dependent paraptosis coincident with proteotoxic stress.", "authors": [{"family": "Sae-Fung", "given": "Apiwit", "initials": "A"}, {"family": "Fadeel", "given": "Bengt", "initials": "B"}], "type": "journal article", "published": "2025-12-12", "journal": {"title": "Cell Commun Signal", "issn": "1478-811X", "volume": "24", "issue": "1", "pages": "47", "issn-l": null}, "abstract": "Copper is essential to all living organisms. However, too much copper is deleterious, and cellular copper content is therefore subject to tight control. Excess copper was recently found to perturb a set of metabolic enzymes in mitochondria, leading to the aggregation of these proteins and the demise of the cell. However, our understanding of the mechanism of copper-dependent cell death remains incomplete. Here, we report that copper ionophore (elesclomol)-induced cell death is calpain-dependent, featuring dilation of the endoplasmic reticulum along with perinuclear clustering of mitochondria. Moreover, elesclomol evoked proteotoxic stress, manifested as a disruption of ubiquitin and proteasome homeostasis, coupled with a conserved heat shock response. Overall, these results have shown that elesclomol promotes calpain-dependent paraptosis with the involvement of both mitochondrial and extramitochondrial compartments of the cell.", "doi": "10.1186/s12964-025-02558-5", "pmid": "41388416", "labels": {"Chemical Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12837948"}, {"db": "pii", "key": "10.1186/s12964-025-02558-5"}], "notes": [], "created": "2026-01-31T17:47:09.857Z", "modified": "2026-01-31T17:47:09.861Z"}, {"entity": "publication", "iuid": "5aa825a515bd4748afa8d655ebf3d0ac", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5aa825a515bd4748afa8d655ebf3d0ac.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5aa825a515bd4748afa8d655ebf3d0ac"}}, "title": "NUDT5 regulates the global efficacy of nucleoside analog drugs by coordinating purine synthesis and PRPP allocation", "authors": [{"family": "Valerie", "given": "Nicholas C K", "initials": "NCK", "orcid": "0000-0002-9423-964X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f1d90c5a1f924c8b97409934dec74b0b.json"}}, {"family": "Alam", "given": "Seher", "initials": "S", "orcid": "0000-0002-8494-832X", "researcher": {"href": "https://publications.scilifelab.se/researcher/034588861fbc437bafe9cf7074ecd7ab.json"}}, {"family": "Hormann", "given": "Femke M", "initials": "FM", "orcid": "0000-0001-5164-3047", "researcher": {"href": "https://publications.scilifelab.se/researcher/79446287545b419aa569359af34b23ce.json"}}, {"family": "Martens", "given": "Ulf", "initials": "U"}, {"family": "Lundgren", "given": "Bo", "initials": "B"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Bostr\u00f6m", "given": "Johan", "initials": "J", "orcid": "0000-0001-5252-4023", "researcher": {"href": "https://publications.scilifelab.se/researcher/2af59464d2c74c27af7a43fb5d1a670e.json"}}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf1e23d9748e4868a4b5e966e423b1a9.json"}}, {"family": "Arvidsson", "given": "Per I", "initials": "PI", "orcid": "0000-0002-9453-6812", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae064b90b750457e80e974947f2dfc7a.json"}}, {"family": "Altun", "given": "Mikael", "initials": "M", "orcid": "0000-0002-6937-6124", "researcher": {"href": "https://publications.scilifelab.se/researcher/4317b773615e476694840e907b7b1a0c.json"}}], "type": "posted-content", "published": "2025-11-20", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2025.11.20.689348", "pmid": null, "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [], "notes": [], "created": "2025-11-25T16:34:20.317Z", "modified": "2025-12-18T18:33:55.727Z"}, {"entity": "publication", "iuid": "cb92a5fa72ae4cd6953839297ce2af22", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cb92a5fa72ae4cd6953839297ce2af22.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cb92a5fa72ae4cd6953839297ce2af22"}}, "title": "A generative deep learning approach to de novo antibiotic design.", "authors": [{"family": "Krishnan", "given": "Aarti", "initials": "A"}, {"family": "Anahtar", "given": "Melis N", "initials": "MN"}, {"family": "Valeri", "given": "Jacqueline A", "initials": "JA"}, {"family": "Jin", "given": "Wengong", "initials": "W"}, {"family": "Donghia", "given": "Nina M", "initials": "NM"}, {"family": "Sieben", "given": "Leif", "initials": "L"}, {"family": "Luttens", "given": "Andreas", "initials": "A"}, {"family": "Zhang", "given": "Yu", "initials": "Y"}, {"family": "Modaresi", "given": "Seyed Majed", "initials": "SM"}, {"family": "Hennes", "given": "Andrew", "initials": "A"}, {"family": "Fromer", "given": "Jenna", "initials": "J"}, {"family": "Bandyopadhyay", "given": "Parijat", "initials": "P"}, {"family": "Chen", "given": "Jonathan C", "initials": "JC"}, {"family": "Rehman", "given": "Danyal", "initials": "D"}, {"family": "Desai", "given": "Ronak", "initials": "R"}, {"family": "Edwards", "given": "Paige", "initials": "P"}, {"family": "Lach", "given": "Ryan S", "initials": "RS"}, {"family": "Aschtgen", "given": "Marie-St\u00e9phanie", "initials": "MS"}, {"family": "Gaborieau", "given": "Margaux", "initials": "M"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M"}, {"family": "Palace", "given": "Samantha G", "initials": "SG"}, {"family": "Omori", "given": "Satotaka", "initials": "S"}, {"family": "Khonde", "given": "Lutete", "initials": "L"}, {"family": "Moroz", "given": "Yurii S", "initials": "YS"}, {"family": "Blough", "given": "Bruce", "initials": "B"}, {"family": "Jin", "given": "Chunyang", "initials": "C"}, {"family": "Loh", "given": "Edmund", "initials": "E"}, {"family": "Grad", "given": "Yonatan H", "initials": "YH"}, {"family": "Saei", "given": "Amir Ata", "initials": "AA"}, {"family": "Coley", "given": "Connor W", "initials": "CW"}, {"family": "Wong", "given": "Felix", "initials": "F"}, {"family": "Collins", "given": "James J", "initials": "JJ"}], "type": "journal article", "published": "2025-10-16", "journal": {"title": "Cell", "issn": "1097-4172", "volume": "188", "issue": "21", "pages": "5962-5979.e22", "issn-l": "0092-8674"}, "abstract": "The antimicrobial resistance crisis necessitates structurally distinct antibiotics. While deep learning approaches can identify antibacterial compounds from existing libraries, structural novelty remains limited. Here, we developed a generative artificial intelligence framework for designing de novo antibiotics through two approaches: a fragment-based method to comprehensively screen >107 chemical fragments in silico against Neisseria gonorrhoeae or Staphylococcus aureus, subsequently expanding promising fragments, and an unconstrained de novo compound generation, each using genetic algorithms and variational autoencoders. Of 24 synthesized compounds, seven demonstrated selective antibacterial activity. Two lead compounds exhibited bactericidal efficacy against multidrug-resistant isolates with distinct mechanisms of action and reduced bacterial burden in vivo in mouse models of N. gonorrhoeae vaginal infection and methicillin-resistant S. aureus skin infection. We further validated structural analogs for both compound classes as antibacterial. Our approach enables the generative deep-learning-guided design of de novo antibiotics, providing a platform for mapping uncharted regions of chemical space.", "doi": "10.1016/j.cell.2025.07.033", "pmid": "40816267", "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0092-8674(25)00855-4"}], "notes": [], "created": "2025-11-25T16:41:24.655Z", "modified": "2025-11-25T16:41:24.698Z"}, {"entity": "publication", "iuid": "276f9dc9c9074208b65c0d97631c4af2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/276f9dc9c9074208b65c0d97631c4af2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/276f9dc9c9074208b65c0d97631c4af2"}}, "title": "Toward a Species Search Engine: KISSE Offers a Rigorous Statistical Framework for Bone Collagen Tandem Mass Spectrometry Data.", "authors": [{"family": "Gharibi", "given": "Hassan", "initials": "H", "orcid": "0000-0002-3072-4929", "researcher": {"href": "https://publications.scilifelab.se/researcher/b85179acfa7e4916ad40ae478d6dcc0a.json"}}, {"family": "Saei", "given": "Amir Ata", "initials": "AA", "orcid": "0000-0002-2639-6328", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1694ffdcd94a55b6c172a854706e0f.json"}}, {"family": "Chernobrovkin", "given": "Alexey L", "initials": "AL"}, {"family": "Lundstrom", "given": "Susanna L", "initials": "SL"}, {"family": "Lyu", "given": "Hezheng", "initials": "H", "orcid": "0009-0008-7995-6473", "researcher": {"href": "https://publications.scilifelab.se/researcher/de932cbcb2c341f7a6544104026c7b1c.json"}}, {"family": "Meng", "given": "Zhaowei", "initials": "Z", "orcid": "0000-0002-7721-2795", "researcher": {"href": "https://publications.scilifelab.se/researcher/60b3f220ebf947779d4b2638d2ccef1c.json"}}, {"family": "Vegvari", "given": "Akos", "initials": "A", "orcid": "0000-0002-1287-0906", "researcher": {"href": "https://publications.scilifelab.se/researcher/74be6e7c877e4f0da6c7ed3747f3ef9d.json"}}, {"family": "Gaetani", "given": "Massimilliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "journal article", "published": "2025-10-00", "journal": {"title": "Adv Sci (Weinh)", "issn": "2198-3844", "volume": "12", "issue": "40", "pages": "e03963", "issn-l": null}, "abstract": "DNA and bone collagen are two key sources of resilient molecular markers used to identify species from their remains. Collagen is more stable than DNA, and thus it is preferred for ancient and degraded samples. Current mass spectrometry-based collagen sequencing approaches are empirical and lack a rigorous statistical framework. Based on the well-developed approaches to protein identification in shotgun proteomics, a first approximation of the species search engine (SSE) is introduced. SSE named KISSE is based on a species-specific library of collagenous peptides that uses both peptide sequences and their relative abundances. The developed statistical model can identify the species and the probability of correct identification, as well as determine the likelihood of the analyzed species not being in the library. The advantages and limitations of the proposed approach, and the possibility of extending it to other tissues is discussed.", "doi": "10.1002/advs.202503963", "pmid": "40787835", "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC12561455"}], "notes": [], "created": "2025-11-25T16:41:57.206Z", "modified": "2025-11-25T16:41:57.260Z"}, {"entity": "publication", "iuid": "cdb29234ff42469f8e1910f10359d71c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cdb29234ff42469f8e1910f10359d71c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cdb29234ff42469f8e1910f10359d71c"}}, "title": "Proteome integral solubility alteration assay for monitoring antibody-antigen cell interactions", "authors": [{"family": "Lu", "given": "Weiqi", "initials": "W"}, {"family": "Lundstrom", "given": "Susanna L", "initials": "SL", "orcid": "0000-0003-2363-4287", "researcher": {"href": "https://publications.scilifelab.se/researcher/916e190e150e465c9e6afc11911bae04.json"}}, {"family": "Hou", "given": "Yaolin", "initials": "Y", "orcid": "0000-0002-2750-4167", "researcher": {"href": "https://publications.scilifelab.se/researcher/3c659cd3e4674b409d4d140adcd6a7dc.json"}}, {"family": "Mukherjee", "given": "Sourav", "initials": "S"}, {"family": "Haeggstr\u00f6m", "given": "Jesper Z", "initials": "JZ", "orcid": "0000-0002-1823-5153", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee1e25240017456f80599973397b4bd6.json"}}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "posted-content", "published": "2025-09-06", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2025.09.04.673944", "pmid": null, "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [], "notes": [], "created": "2025-11-25T16:24:40.307Z", "modified": "2025-12-18T19:09:30.114Z"}, {"entity": "publication", "iuid": "a8fbcd4a221c4de2a1151348bd4c9304", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a8fbcd4a221c4de2a1151348bd4c9304.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a8fbcd4a221c4de2a1151348bd4c9304"}}, "title": "Diverse oncogenes use common mechanisms to drive growth of major forms of human cancer.", "authors": [{"family": "Kauko", "given": "Otto", "initials": "O", "orcid": "0000-0001-8948-9452", "researcher": {"href": "https://publications.scilifelab.se/researcher/c5390cad42a0409f8b66f56ab23ca232.json"}}, {"family": "Turunen", "given": "Mikko", "initials": "M"}, {"family": "Pihlajamaa", "given": "P\u00e4ivi", "initials": "P", "orcid": "0000-0001-9725-6907", "researcher": {"href": "https://publications.scilifelab.se/researcher/1171591a6a724f50a631d34948c6f14a.json"}}, {"family": "H\u00e4kkinen", "given": "Antti", "initials": "A", "orcid": "0000-0002-8081-1588", "researcher": {"href": "https://publications.scilifelab.se/researcher/b00bca666f344d4980a97bbdba20361e.json"}}, {"family": "Queiroz", "given": "Rayner M L", "initials": "RML"}, {"family": "P\u00e4\u00e4kk\u00f6nen", "given": "Mirva", "initials": "M"}, {"family": "Ventel\u00e4", "given": "Sami", "initials": "S"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Lundstr\u00f6m", "given": "Susanna L", "initials": "SL", "orcid": "0000-0003-2363-4287", "researcher": {"href": "https://publications.scilifelab.se/researcher/916e190e150e465c9e6afc11911bae04.json"}}, {"family": "Murgia", "given": "Antonio", "initials": "A"}, {"family": "Sahu", "given": "Biswajyoti", "initials": "B", "orcid": "0000-0001-6576-5440", "researcher": {"href": "https://publications.scilifelab.se/researcher/283b12ad225d4fb2b4e38b7f10c026d4.json"}}, {"family": "Routila", "given": "Johannes", "initials": "J", "orcid": "0000-0001-5385-7065", "researcher": {"href": "https://publications.scilifelab.se/researcher/71ee18226e6e4a42ae83b7106ca8b343.json"}}, {"family": "Wei", "given": "Gong-Hong", "initials": "G"}, {"family": "Irjala", "given": "Heikki", "initials": "H", "orcid": "0000-0003-3054-4677", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf759b807e9640aab8fcadbad0c60662.json"}}, {"family": "Griffin", "given": "Julian L", "initials": "JL", "orcid": "0000-0003-1336-7744", "researcher": {"href": "https://publications.scilifelab.se/researcher/98e91146412f4bd2a0bed9331efee8d2.json"}}, {"family": "Lilley", "given": "Kathryn S", "initials": "KS", "orcid": "0000-0003-0594-6543", "researcher": {"href": "https://publications.scilifelab.se/researcher/77b4e7e18a88455199308070d6da7ea3.json"}}, {"family": "Kivioja", "given": "Teemu", "initials": "T", "orcid": "0000-0002-7732-2177", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c318f57c5ce4f4bb747e19514caa907.json"}}, {"family": "Hautaniemi", "given": "Sampsa", "initials": "S", "orcid": "0000-0002-7749-2694", "researcher": {"href": "https://publications.scilifelab.se/researcher/a29cabf8ec5e4f78b9d14984a60c3e84.json"}}, {"family": "Taipale", "given": "Jussi", "initials": "J", "orcid": "0000-0003-4204-0951", "researcher": {"href": "https://publications.scilifelab.se/researcher/43111333f8a84b2cbbceb64d4e1e3bc5.json"}}], "type": "journal article", "published": "2025-08-22", "journal": {"title": "Sci Adv", "issn": "2375-2548", "issn-l": "2375-2548", "volume": "11", "issue": "34", "pages": "eadt1798"}, "abstract": "Mutations in numerous genes contribute to human cancer, with different oncogenic lesions prevalent in different cancer types. However, the malignant phenotype is simple, characterized by unrestricted cell growth, invasion, and often metastasis. One possible hypothesis explaining this dichotomy is that cancer genes regulate common targets, which then function as master regulators of essential cancer phenotypes. To identify mechanisms that drive the most fundamental feature shared by all tumors-unrestricted cell proliferation-we used a multiomic approach, which identified translation and ribosome biogenesis as common targets of major oncogenic pathways across cancer types. Proteomic analysis of tumors and functional studies of cell cultures established nucleolar and coiled-body phosphoprotein 1 as a key node, whose convergent regulation, both transcriptionally and posttranslationally, is critical for tumor cell proliferation. Our results indicate that lineage-specific oncogenic pathways regulate the same set of targets for growth control, revealing key downstream nodes that could be targeted for therapy or chemoprevention.", "doi": "10.1126/sciadv.adt1798", "pmid": "40834066", "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC13155486"}], "notes": [], "created": "2025-11-25T16:41:01.046Z", "modified": "2026-05-25T19:26:02.282Z"}, {"entity": "publication", "iuid": "6bfd9db1c38b49c49158044c0155d00d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6bfd9db1c38b49c49158044c0155d00d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6bfd9db1c38b49c49158044c0155d00d"}}, "title": "Thioredoxin Reductase 1 inhibition triggers ferroptosis in KRAS-independent lung cancers.", "authors": [{"family": "Andreani", "given": "Cristina", "initials": "C", "orcid": "0000-0003-3245-670X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ac8d24e06e2949b59784539dc93e9a1e.json"}}, {"family": "Bartolacci", "given": "Caterina", "initials": "C", "orcid": "0000-0003-2002-7721", "researcher": {"href": "https://publications.scilifelab.se/researcher/4876eab40d6f496da30ea338ede8e8e1.json"}}, {"family": "Melegari", "given": "Margherita", "initials": "M", "orcid": "0000-0003-3565-5560", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ad61d725ed8433c9e4469312bcce77f.json"}}, {"family": "Sargentoni", "given": "Nicola", "initials": "N", "orcid": "0009-0009-2735-3440", "researcher": {"href": "https://publications.scilifelab.se/researcher/e478ff01e2e24fe8bbbf3331b125d093.json"}}, {"family": "Luciani", "given": "Lorenzo", "initials": "L", "orcid": "0000-0002-9000-7454", "researcher": {"href": "https://publications.scilifelab.se/researcher/806ba2ac1b9f461eb25549b4b81fd1d9.json"}}, {"family": "Marucci", "given": "Agnese", "initials": "A"}, {"family": "Galeazzi", "given": "Roberta", "initials": "R", "orcid": "0000-0003-1792-654X", "researcher": {"href": "https://publications.scilifelab.se/researcher/891fb9c56107468a8cce385d8bb402b6.json"}}, {"family": "DeNicola", "given": "Gina M", "initials": "GM", "orcid": "0000-0001-6611-6696", "researcher": {"href": "https://publications.scilifelab.se/researcher/e19a7cc8adae4fd482db8d1e44adbf23.json"}}, {"family": "Kilgore", "given": "Jessica", "initials": "J", "orcid": "0000-0001-9138-2099", "researcher": {"href": "https://publications.scilifelab.se/researcher/340f210063894be2b5a7a3edc73a9f64.json"}}, {"family": "Williams", "given": "Noelle", "initials": "N", "orcid": "0000-0003-1894-5742", "researcher": {"href": "https://publications.scilifelab.se/researcher/69f9dcee6ec441abbf0bc8d19b1cdeb2.json"}}, {"family": "Berto", "given": "Stefano", "initials": "S", "orcid": "0000-0001-9028-9458", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e144d40db50454caf117f24e57a320a.json"}}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Pattabhi", "given": "Prasad", "initials": "P", "orcid": "0000-0002-8437-7838", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ff340a9b68a46f7b87225a63767f6b9.json"}}, {"family": "Osman", "given": "Sagid S", "initials": "SS"}, {"family": "Mansour", "given": "Ahmad T", "initials": "AT"}, {"family": "Pucciarelli", "given": "Stefania", "initials": "S", "orcid": "0000-0003-2137-5517", "researcher": {"href": "https://publications.scilifelab.se/researcher/6ee3c9bf3ffc485a8686a08aef7e4ca8.json"}}, {"family": "Galassi", "given": "Rossana", "initials": "R", "orcid": "0000-0002-8025-9615", "researcher": {"href": "https://publications.scilifelab.se/researcher/97a7ad071ad4410dad92fe45c56e61e4.json"}}, {"family": "Scaglioni", "given": "Pier Paolo", "initials": "PP", "orcid": "0000-0002-6036-5138", "researcher": {"href": "https://publications.scilifelab.se/researcher/898e0ff87b6949129b39faae85c5346c.json"}}], "type": "journal article", "published": "2025-07-30", "journal": {"title": "bioRxiv", "issn": "2692-8205", "issn-l": null}, "abstract": "Lung cancers that harbor wild type KRAS (KRAS-WT) represent a molecularly diverse subset of tumors that often lack targeted therapeutic options. Using synthesized gold(I)-based inhibitors, a multi-omics approach, and functional validation, we identified Thioredoxin reductase 1 (TXNRD1), encoding as a selective vulnerability in KRAS-WT and oncogenic KRAS mutant (KM)-independent lung cancer (LC). Mechanistically, TRXR1 blockade induces ferroptosis through glutathione depletion, lipid reactive oxygen species (ROS) accumulation, and HMOX1-dependent iron overload in KRAS-WT LC both in vitro and in vivo. Furthermore, while KM LC cells are intrinsically resistant to TRXR1 inhibition, KMLC cells that acquire resistance to KRAS inhibitors (KRASi) undergo a redox shift that renders them sensitive to TRXR1 inhibition, uncovering a potential novel therapeutic vulnerability in KRASi-refractory tumors. These findings establish TRXR1 as a targetable redox checkpoint in KRAS-WT and KRASi-resistant lung cancers and support further development of TRXR1 inhibitors.", "doi": "10.1101/2025.07.25.666783", "pmid": "40766571", "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC12324224"}, {"db": "pii", "key": "2025.07.25.666783"}, {"db": "figshare", "key": "10.25452/figshare.plus.24667905.v2"}], "notes": [], "created": "2025-11-25T16:35:13.732Z", "modified": "2025-11-25T16:42:16.937Z"}, {"entity": "publication", "iuid": "8e3c080a6b6f4c1494f64bbfe3ee1dc4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8e3c080a6b6f4c1494f64bbfe3ee1dc4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8e3c080a6b6f4c1494f64bbfe3ee1dc4"}}, "title": "Identification of a small molecule targeting EPLIN as a novel strategy for the treatment of pediatric neuroblastoma and medulloblastoma.", "authors": [{"family": "Lindell", "given": "Emma", "initials": "E", "orcid": "0009-0001-2785-946X", "researcher": {"href": "https://publications.scilifelab.se/researcher/667fca56e7c74aa7984daf5dac4bbc2e.json"}}, {"family": "Guo", "given": "Jing", "initials": "J", "orcid": "0000-0002-6399-3877", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e778f67395b491daec1b80d805ab6bd.json"}}, {"family": "Zhao", "given": "Miao", "initials": "M", "orcid": "0000-0002-4895-1177", "researcher": {"href": "https://publications.scilifelab.se/researcher/b9c4e2515b414dee94aaeca71569699b.json"}}, {"family": "Rameika", "given": "Natallia", "initials": "N"}, {"family": "Lu", "given": "Xi", "initials": "X"}, {"family": "Wacker", "given": "Tabea", "initials": "T"}, {"family": "Zhong", "given": "Lei", "initials": "L"}, {"family": "Bergstr\u00f6m", "given": "Tobias", "initials": "T"}, {"family": "Svanberg", "given": "Sara", "initials": "S"}, {"family": "Chowdhury", "given": "Azazul I", "initials": "AI"}, {"family": "Bergsten", "given": "Peter", "initials": "P"}, {"family": "Chen", "given": "Xingqi", "initials": "X", "orcid": "0000-0002-5657-2839", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef7ddc09e57745909175e41ac2d1b647.json"}}, {"family": "Bexell", "given": "Daniel", "initials": "D"}, {"family": "Swartling", "given": "Fredrik J", "initials": "FJ", "orcid": "0000-0002-8460-4367", "researcher": {"href": "https://publications.scilifelab.se/researcher/69679cebbc90496f9c5b32f56d966654.json"}}, {"family": "Sj\u00f6blom", "given": "Tobias", "initials": "T", "orcid": "0000-0001-6668-4140", "researcher": {"href": "https://publications.scilifelab.se/researcher/909f00a5bf6e465f9ff560b12bcd863a.json"}}, {"family": "Zhang", "given": "Xiaonan", "initials": "X", "orcid": "0000-0003-4359-9079", "researcher": {"href": "https://publications.scilifelab.se/researcher/306b1ef8c6904d6b936e11442b4515f4.json"}}], "type": "journal article", "published": "2025-07-23", "journal": {"title": "Cell Death Dis", "issn": "2041-4889", "issn-l": "2041-4889", "volume": "16", "issue": "1", "pages": "554"}, "abstract": "Amplification of the MYCN proto-oncogene serves as a key marker of aggressive disease and poor treatment outcomes in certain pediatric tumors originating from the nervous system, including neuroblastoma and medulloblastoma. However, the complex nature of the challenging MYCN protein underscores the urgent need for additional targets and therapies to tackle neuroblastoma and medulloblastoma. In this study, with a primary focus on neuroblastoma and the aim of also benefiting children with medulloblastoma, we identified FLIX5, a small compound that exhibits broad cytotoxicity against both neuroblastoma and medulloblastoma cells, primarily by triggering apoptosis. Furthermore, FLIX5 enhances the cholesterol dependency of neuroblastoma cells under conditions where mitochondrial function is impaired. FLIX5 as well shows a synergistic effect when combined with vincristine, a conventional anticancer drug, against neuroblastoma cells and organoids. Through proteome integral solubility alteration, computational molecular docking predictions, and cellular thermal shift assays for target identification and validation, FLIX5 reveals EPLIN (Epithelial Protein Lost In Neoplasm) as a previously unexplored drug target. EPLIN is involved in several cellular processes, including cholesterol uptake and mitochondrial function. The discovery of FLIX5 targeting EPLIN presents new opportunities for treating malignant pediatric tumors, with the potential to target chemoresistant dormant cancer cells and broaden its therapeutic applications to other tumor types.", "doi": "10.1038/s41419-025-07876-7", "pmid": "40701975", "labels": {"NGI Single cell": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Chemical Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12287531"}, {"db": "pii", "key": "10.1038/s41419-025-07876-7"}], "notes": [], "created": "2025-09-30T09:25:55.225Z", "modified": "2025-11-25T17:06:41.935Z"}, {"entity": "publication", "iuid": "3a5b4226b65d4c05a3c20c75d6d2d57f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3a5b4226b65d4c05a3c20c75d6d2d57f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3a5b4226b65d4c05a3c20c75d6d2d57f"}}, "title": "HigH-ratiO partiaL proteolysiS with carriER proteome (HOLSER) Enables Global Structure Profiling and Site-resolved Elucidation of Ligand-Protein Interactions", "authors": [{"family": "Zhang", "given": "Xuepei", "initials": "X"}, {"family": "Sokolova", "given": "Bohdana", "initials": "B"}, {"family": "Meng", "given": "Zhaowei", "initials": "Z", "orcid": "0000-0002-7721-2795", "researcher": {"href": "https://publications.scilifelab.se/researcher/60b3f220ebf947779d4b2638d2ccef1c.json"}}, {"family": "Gharibi", "given": "Hassan", "initials": "H", "orcid": "0000-0002-3072-4929", "researcher": {"href": "https://publications.scilifelab.se/researcher/b85179acfa7e4916ad40ae478d6dcc0a.json"}}, {"family": "Lyu", "given": "Hezheng", "initials": "H", "orcid": "0009-0008-7995-6473", "researcher": {"href": "https://publications.scilifelab.se/researcher/de932cbcb2c341f7a6544104026c7b1c.json"}}, {"family": "Ata Saei", "given": "Amir", "initials": "A"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "posted-content", "published": "2025-07-15", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2025.07.11.664381", "pmid": null, "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [], "notes": [], "created": "2025-11-25T16:22:59.508Z", "modified": "2025-12-18T19:12:11.165Z"}, {"entity": "publication", "iuid": "6e499e6478cc4696a5a0a6a7534b3c6c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6e499e6478cc4696a5a0a6a7534b3c6c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6e499e6478cc4696a5a0a6a7534b3c6c"}}, "title": "A cell-based degrader assessment platform facilitates discovery of functional NUDT5 PROTACs", "authors": [{"family": "Alam", "given": "Seher", "initials": "S", "orcid": "0000-0002-8494-832X", "researcher": {"href": "https://publications.scilifelab.se/researcher/034588861fbc437bafe9cf7074ecd7ab.json"}}, {"family": "Pires", "given": "Maria J", "initials": "MJ", "orcid": "0009-0007-0384-091X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e7a891756624e5583914ea7b2d3176e.json"}}, {"family": "Tidestav", "given": "Gabriel", "initials": "G"}, {"family": "Jemth", "given": "Ann Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd07c6c543544af1a904e039f73ba857.json"}}, {"family": "Eklund", "given": "Julia", "initials": "J", "orcid": "0009-0000-7449-2456", "researcher": {"href": "https://publications.scilifelab.se/researcher/96b04b6202964265b671901bcf4b66b4.json"}}, {"family": "Klingeg\u00e5rd", "given": "Fredrik", "initials": "F", "orcid": "0000-0001-6280-3894", "researcher": {"href": "https://publications.scilifelab.se/researcher/87593a4ce9ba4b3d8d1e3bc6836d42af.json"}}, {"family": "Caraballo", "given": "R\u00e9mi", "initials": "R", "orcid": "0000-0001-5912-8429", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e3194cd076e4eac95e029cfe4adefbc.json"}}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Rotilli", "given": "Dante", "initials": "D", "orcid": "0000-0002-8428-8763", "researcher": {"href": "https://publications.scilifelab.se/researcher/4939561c24b14fbbbdd82aa08a9e1ab5.json"}}, {"family": "van den Elzen", "given": "Siebe", "initials": "S"}, {"family": "van Berkum", "given": "Eri", "initials": "E"}, {"family": "Wallner", "given": "Olov", "initials": "O", "orcid": "0000-0002-6481-237X", "researcher": {"href": "https://publications.scilifelab.se/researcher/83eb2f7ee2f34f2cbacaae2dadcd90e9.json"}}, {"family": "Malmstr\u00f6m", "given": "Jonas", "initials": "J"}, {"family": "Arvidsson", "given": "Per I", "initials": "PI", "orcid": "0000-0002-9453-6812", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae064b90b750457e80e974947f2dfc7a.json"}}, {"family": "Valerie", "given": "Nicholas C K", "initials": "NCK", "orcid": "0000-0002-9423-964X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f1d90c5a1f924c8b97409934dec74b0b.json"}}, {"family": "Altun", "given": "Mikael", "initials": "M", "orcid": "0000-0002-6937-6124", "researcher": {"href": "https://publications.scilifelab.se/researcher/4317b773615e476694840e907b7b1a0c.json"}}], "type": "posted-content", "published": "2025-06-19", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2025.06.13.659494", "pmid": null, "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [], "notes": [], "created": "2025-11-25T16:38:01.820Z", "modified": "2025-12-18T19:14:22.271Z"}, {"entity": "publication", "iuid": "87b7ae2910fe4078a07ec298cbfaae7c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/87b7ae2910fe4078a07ec298cbfaae7c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/87b7ae2910fe4078a07ec298cbfaae7c"}}, "title": "Above-Filter Digestion Proteomics reveals drug targets and localizes ligand binding site", "authors": [{"family": "Sokolova", "given": "Bohdana", "initials": "B"}, {"family": "Gharibi", "given": "Hassan", "initials": "H", "orcid": "0000-0002-3072-4929", "researcher": {"href": "https://publications.scilifelab.se/researcher/b85179acfa7e4916ad40ae478d6dcc0a.json"}}, {"family": "Jafari", "given": "Maryam", "initials": "M"}, {"family": "Lyu", "given": "Hezheng", "initials": "H", "orcid": "0009-0008-7995-6473", "researcher": {"href": "https://publications.scilifelab.se/researcher/de932cbcb2c341f7a6544104026c7b1c.json"}}, {"family": "Lovera", "given": "Silvia", "initials": "S"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Saei", "given": "Amir Ata", "initials": "AA", "orcid": "0000-0002-2639-6328", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1694ffdcd94a55b6c172a854706e0f.json"}}, {"family": "Zubarev", "given": "Roman", "initials": "R", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "posted-content", "published": "2025-03-13", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2025.03.11.642584", "pmid": null, "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [], "notes": [], "created": "2025-11-25T16:34:50.393Z", "modified": "2025-12-18T19:19:00.493Z"}, {"entity": "publication", "iuid": "b1f09543ec4041a8b1f9fbddd90cf8e3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b1f09543ec4041a8b1f9fbddd90cf8e3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b1f09543ec4041a8b1f9fbddd90cf8e3"}}, "title": "One-Pot Time-Induced Proteome Integral Solubility Alteration Assay for Automated and Sensitive Drug-Target Identification.", "authors": [{"family": "Meng", "given": "Zhaowei", "initials": "Z", "orcid": "0000-0002-7721-2795", "researcher": {"href": "https://publications.scilifelab.se/researcher/60b3f220ebf947779d4b2638d2ccef1c.json"}}, {"family": "Saei", "given": "Amir Ata", "initials": "AA"}, {"family": "Lyu", "given": "Hezheng", "initials": "H"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "journal article", "published": "2024-11-20", "journal": {"title": "Anal. Chem.", "issn": "1520-6882", "issn-l": "0003-2700", "volume": null, "issue": null, "pages": null}, "abstract": "The proteome integral solubility alteration (PISA) assay is widely used for identifying drug targets, but it is labor-intensive and time-consuming and requires a substantial amount of biological sample. Aiming at enabling automation and greatly reducing the sample amount, we developed one-pot time-induced (OPTI)-PISA. Here, we demonstrate OPTI-PISA performance on identifying targets of multiple drugs in cell lysate and scaling down the sample amount to sub-microgram levels, making the PISA method suitable for NanoProteomics. OPTI-PISA can be implemented using only the standard equipment of a proteomics lab.", "doi": "10.1021/acs.analchem.4c05127", "pmid": "39567183", "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [], "notes": [], "created": "2024-11-22T13:35:33.664Z", "modified": "2024-11-22T13:35:52.123Z"}, {"entity": "publication", "iuid": "885b80bceacf4a2bbebcd0b600cc9ccd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/885b80bceacf4a2bbebcd0b600cc9ccd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/885b80bceacf4a2bbebcd0b600cc9ccd"}}, "title": "Merging multi-omics with proteome integral solubility alteration unveils antibiotic mode of action.", "authors": [{"family": "Maity", "given": "Ritwik", "initials": "R", "orcid": "0000-0003-4058-2888", "researcher": {"href": "https://publications.scilifelab.se/researcher/18d6c3d2bf5644c9912e1f70515436ef.json"}}, {"family": "Zhang", "given": "Xuepei", "initials": "X"}, {"family": "Liberati", "given": "Francesca Romana", "initials": "FR"}, {"family": "Scribani Rossi", "given": "Chiara", "initials": "C", "orcid": "0000-0003-4855-4240", "researcher": {"href": "https://publications.scilifelab.se/researcher/daf0d849f9db44798a85e486b6892b7f.json"}}, {"family": "Cutruzzol\u00e1", "given": "Francesca", "initials": "F"}, {"family": "Rinaldo", "given": "Serena", "initials": "S", "orcid": "0000-0003-0682-023X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a396dc50da1442c8ad4efee8c8cac003.json"}}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M"}, {"family": "A\u00ednsa", "given": "Jos\u00e9 Antonio", "initials": "JA", "orcid": "0000-0003-2076-844X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c0b596fdedba47968a713c4f3484c93d.json"}}, {"family": "Sancho", "given": "Javier", "initials": "J", "orcid": "0000-0002-2879-9200", "researcher": {"href": "https://publications.scilifelab.se/researcher/0a191843b677445f9ffec338aaff9453.json"}}], "type": "journal article", "published": "2024-09-27", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "13", "issn-l": "2050-084X"}, "abstract": "Antimicrobial resistance is responsible for an alarming number of deaths, estimated at 5 million per year. To combat priority pathogens, like Helicobacter pylori, the development of novel therapies is of utmost importance. Understanding the molecular alterations induced by medications is critical for the design of multi-targeting treatments capable of eradicating the infection and mitigating its pathogenicity. However, the application of bulk omics approaches for unraveling drug molecular mechanisms of action is limited by their inability to discriminate between target-specific modifications and off-target effects. This study introduces a multi-omics method to overcome the existing limitation. For the first time, the Proteome Integral Solubility Alteration (PISA) assay is utilized in bacteria in the PISA-Express format to link proteome solubility with different and potentially immediate responses to drug treatment, enabling us the resolution to understand target-specific modifications and off-target effects. This study introduces a comprehensive method for understanding drug mechanisms and optimizing the development of multi-targeting antimicrobial therapies.", "doi": "10.7554/eLife.96343", "pmid": "39329363", "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11434622"}, {"db": "pii", "key": "96343"}], "notes": [], "created": "2024-09-30T08:01:03.163Z", "modified": "2024-09-30T08:01:13.365Z"}, {"entity": "publication", "iuid": "7469a2b8bd88408a99fdf9074d6dce9e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7469a2b8bd88408a99fdf9074d6dce9e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7469a2b8bd88408a99fdf9074d6dce9e"}}, "title": "Gel-Assisted Proteome Position Integral Shift Assay Returns Molecular Weight to Shotgun Proteomics and Identifies Caspase 3 Substrates.", "authors": [{"family": "Meng", "given": "Zhaowei", "initials": "Z"}, {"family": "Saei", "given": "Amir Ata", "initials": "AA", "orcid": "0000-0002-2639-6328", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1694ffdcd94a55b6c172a854706e0f.json"}}, {"family": "Gharibi", "given": "Hassan", "initials": "H", "orcid": "0000-0002-3072-4929", "researcher": {"href": "https://publications.scilifelab.se/researcher/b85179acfa7e4916ad40ae478d6dcc0a.json"}}, {"family": "Zhang", "given": "Xuepei", "initials": "X"}, {"family": "Lyu", "given": "Hezheng", "initials": "H"}, {"family": "Lundstr\u00f6m", "given": "Susanna L", "initials": "SL"}, {"family": "V\u00e9gv\u00e1ri", "given": "\u00c1kos", "initials": "\u00c1", "orcid": "0000-0002-1287-0906", "researcher": {"href": "https://publications.scilifelab.se/researcher/74be6e7c877e4f0da6c7ed3747f3ef9d.json"}}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "journal article", "published": "2024-08-20", "journal": {"title": "Anal. Chem.", "issn": "1520-6882", "volume": "96", "issue": "33", "pages": "13533-13541", "issn-l": "0003-2700"}, "abstract": "Here, we present a high-throughput virtual top-down proteomics approach that restores the molecular weight (MW) information in shotgun proteomics and demonstrates its utility in studying proteolytic events in programmed cell death. With gel-assisted proteome position integral shift (GAPPIS), we quantified over 7000 proteins in staurosporine-induced apoptotic HeLa cells and identified 84 proteins exhibiting in a statistically significant manner at least two of the following features: (i) a negative MW shift; (ii) an elevated ratio in a pair of a semitryptic and tryptic peptide, (iii) a negative shift in the standard deviation of MW estimated for different peptides, and (iv) a negative shift in skewness of the same data. Of these proteins, 58 molecules were previously unreported caspase 3 substrates. Further analysis identified the preferred cleavage sites consistent with the known caspase cleavages after the DXXD motif. As a powerful tool for high-throughput MW analysis simultaneously with the conventional expression analysis, the GAPPIS assay can prove useful in studying a broad range of biological processes involving proteolytic events.", "doi": "10.1021/acs.analchem.4c02051", "pmid": "39110629", "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [], "notes": [], "created": "2024-08-21T16:03:52.664Z", "modified": "2024-08-21T16:03:52.890Z"}, {"entity": "publication", "iuid": "53bc595db3134818b46d92120a3baa78", "links": {"self": {"href": "https://publications.scilifelab.se/publication/53bc595db3134818b46d92120a3baa78.json"}, "display": {"href": "https://publications.scilifelab.se/publication/53bc595db3134818b46d92120a3baa78"}}, "title": "Multifaceted Proteome Analysis at Solubility, Redox, and Expression Dimensions for Target Identification.", "authors": [{"family": "Saei", "given": "Amir A", "initials": "AA"}, {"family": "Lundin", "given": "Albin", "initials": "A"}, {"family": "Lyu", "given": "Hezheng", "initials": "H"}, {"family": "Gharibi", "given": "Hassan", "initials": "H"}, {"family": "Luo", "given": "Huqiao", "initials": "H"}, {"family": "Teppo", "given": "Jaakko", "initials": "J"}, {"family": "Zhang", "given": "Xuepei", "initials": "X"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M"}, {"family": "V\u00e9gv\u00e1ri", "given": "\u00c1kos", "initials": "\u00c1"}, {"family": "Holmdahl", "given": "Rikard", "initials": "R"}, {"family": "Gygi", "given": "Steven P", "initials": "SP"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "journal article", "published": "2024-08-09", "journal": {"title": "Adv Sci (Weinh)", "issn": "2198-3844", "pages": "e2401502", "issn-l": null}, "abstract": "Multifaceted interrogation of the proteome deepens the system-wide understanding of biological systems; however, mapping the redox changes in the proteome has so far been significantly more challenging than expression and solubility/stability analyses. Here, the first high-throughput redox proteomics approach integrated with expression analysis (REX) is devised and combined with the Proteome Integral Solubility Alteration (PISA) assay. The whole PISA-REX experiment with up to four biological replicates can be multiplexed into a single tandem mass tag TMTpro set. For benchmarking this compact tool, HCT116 cells treated with auranofin are analyzed, showing great improvement compared with previous studies. PISA-REX is then applied to study proteome remodeling upon stimulation of human monocytes by interferon \u03b1 (IFN-\u03b1). Applying this tool to study the proteome changes in plasmacytoid dendritic cells (pDCs) isolated from wild-type versus Ncf1-mutant mice treated with interferon \u03b1, shows that NCF1 deficiency enhances the STAT1 pathway and modulates the expression, solubility, and redox state of interferon-induced proteins. Providing comprehensive multifaceted information on the proteome, the compact PISA-REX has the potential to become an industry standard in proteomics and to open new windows into the biology of health and disease.", "doi": "10.1002/advs.202401502", "pmid": "39120068", "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [], "notes": [], "created": "2024-08-21T16:04:05.803Z", "modified": "2024-08-21T16:04:05.836Z"}, {"entity": "publication", "iuid": "2cd83bb48a16401c9977dbc5ffaf2627", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2cd83bb48a16401c9977dbc5ffaf2627.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2cd83bb48a16401c9977dbc5ffaf2627"}}, "title": "A chemical inhibitor of IST1-CHMP1B interaction impairs endosomal recycling and induces noncanonical LC3 lipidation.", "authors": [{"family": "Knyazeva", "given": "Anastasia", "initials": "A"}, {"family": "Li", "given": "Shuang", "initials": "S", "orcid": "0000-0001-7708-0166", "researcher": {"href": "https://publications.scilifelab.se/researcher/b0a0ec3547924f43854a957662cd5089.json"}}, {"family": "Corkery", "given": "Dale P", "initials": "DP", "orcid": "0000-0001-7930-0134", "researcher": {"href": "https://publications.scilifelab.se/researcher/42e668ad5ea8458b8d0eebc3c653a62e.json"}}, {"family": "Shankar", "given": "Kasturika", "initials": "K", "orcid": "0000-0002-0011-3756", "researcher": {"href": "https://publications.scilifelab.se/researcher/4487e20554dc47688cd5d930c2ca1f74.json"}}, {"family": "Herzog", "given": "Laura K", "initials": "LK", "orcid": "0000-0002-3322-7864", "researcher": {"href": "https://publications.scilifelab.se/researcher/b1e8cfcb24a144d196251f02ab95db4d.json"}}, {"family": "Zhang", "given": "Xuepei", "initials": "X"}, {"family": "Singh", "given": "Birendra", "initials": "B", "orcid": "0000-0002-7246-1442", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a37eae28b0b45678502b7be34dbae99.json"}}, {"family": "Niggemeyer", "given": "Georg", "initials": "G"}, {"family": "Grill", "given": "David", "initials": "D"}, {"family": "Gilthorpe", "given": "Jonathan D", "initials": "JD", "orcid": "0000-0002-6884-4774", "researcher": {"href": "https://publications.scilifelab.se/researcher/7eb2a4f38fdc4e0db2516a17d9abdf06.json"}}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Carlson", "given": "Lars-Anders", "initials": "LA", "orcid": "0000-0003-2342-6488", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba0e366ce21e49b48212bbed5a0a7bd1.json"}}, {"family": "Waldmann", "given": "Herbert", "initials": "H", "orcid": "0000-0002-9606-7247", "researcher": {"href": "https://publications.scilifelab.se/researcher/54124c0b6aaa4711ab41a2492264fd9a.json"}}, {"family": "Wu", "given": "Yao-Wen", "initials": "YW", "orcid": "0000-0002-2573-8736", "researcher": {"href": "https://publications.scilifelab.se/researcher/d7fe2a390f534022b4e9a85f986747c7.json"}}], "type": "journal article", "published": "2024-04-23", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "issn-l": "0027-8424", "volume": "121", "issue": "17", "pages": "e2317680121"}, "abstract": "The endosomal sorting complex required for transport (ESCRT) machinery constitutes multisubunit protein complexes that play an essential role in membrane remodeling and trafficking. ESCRTs regulate a wide array of cellular processes, including cytokinetic abscission, cargo sorting into multivesicular bodies (MVBs), membrane repair, and autophagy. Given the versatile functionality of ESCRTs, and the intricate organizational structure of the ESCRT machinery, the targeted modulation of distinct ESCRT complexes is considerably challenging. This study presents a pseudonatural product targeting IST1-CHMP1B within the ESCRT-III complexes. The compound specifically disrupts the interaction between IST1 and CHMP1B, thereby inhibiting the formation of IST1-CHMP1B copolymers essential for normal-topology membrane scission events. While the compound has no impact on cytokinesis, MVB sorting, or biogenesis of extracellular vesicles, it rapidly inhibits transferrin receptor recycling in cells, resulting in the accumulation of transferrin in stalled sorting endosomes. Stalled endosomes become decorated by lipidated LC3, suggesting a link between noncanonical LC3 lipidation and inhibition of the IST1-CHMP1B complex.", "doi": "10.1073/pnas.2317680121", "pmid": "38635626", "labels": {"Chemical Proteomics": "Collaborative", "Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11047075"}], "notes": [], "created": "2024-07-25T13:10:40.169Z", "modified": "2024-11-27T11:33:55.833Z"}, {"entity": "publication", "iuid": "ead69b2d5e3744979b7927407e758443", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ead69b2d5e3744979b7927407e758443.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ead69b2d5e3744979b7927407e758443"}}, "title": "Dual molecule targeting HDAC6 leads to intratumoral CD4+ cytotoxic lymphocytes recruitment through MHC-II upregulation on lung cancer cells.", "authors": [{"family": "Ducellier", "given": "Sarah", "initials": "S"}, {"family": "Demeules", "given": "M\u00e9lanie", "initials": "M"}, {"family": "Letribot", "given": "Boris", "initials": "B"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M"}, {"family": "Michaudel", "given": "Chlo\u00e9", "initials": "C"}, {"family": "Sokol", "given": "Harry", "initials": "H"}, {"family": "Hamze", "given": "Abdallah", "initials": "A"}, {"family": "Alami", "given": "Mouad", "initials": "M"}, {"family": "Nascimento", "given": "M\u00e9gane", "initials": "M", "orcid": "0000-0001-9106-9596", "researcher": {"href": "https://publications.scilifelab.se/researcher/4bd9e31781164c06bbca54f3eb99f12d.json"}}, {"family": "Apcher", "given": "S\u00e9bastien", "initials": "S", "orcid": "0000-0002-4434-5022", "researcher": {"href": "https://publications.scilifelab.se/researcher/cc4dc7f630ee4f74ba654cdab4d90468.json"}}], "type": "journal article", "published": "2024-04-11", "journal": {"title": "J Immunother Cancer", "issn": "2051-1426", "volume": "12", "issue": "4", "issn-l": null}, "abstract": "Despite the current therapeutic treatments including surgery, chemotherapy, radiotherapy and more recently immunotherapy, the mortality rate of lung cancer stays high. Regarding lung cancer, epigenetic modifications altering cell cycle, angiogenesis and programmed cancer cell death are therapeutic targets to combine with immunotherapy to improve treatment success. In a recent study, we uncovered that a molecule called QAPHA ((E)-3-(5-((2-cyanoquinolin-4-yl)(methyl)amino)-2-methoxyphenyl)-N-hydroxyacrylamide) has a dual function as both a tubulin polymerization and HDAC inhibitors. Here, we investigate the impact of this novel dual inhibitor on the immune response to lung cancer.\n\nTo elucidate the mechanism of action of QAPHA, we conducted a chemical proteomics analysis. Using an in vivo mouse model of lung cancer (TC-1 tumor cells), we assessed the effects of QAPHA on tumor regression. Tumor infiltrating immune cells were characterized by flow cytometry.\n\nIn this study, we first showed that QAPHA effectively inhibited histone deacetylase 6, leading to upregulation of HSP90, cytochrome C and caspases, as revealed by proteomic analysis. We confirmed that QAPHA induces immunogenic cell death (ICD) by expressing calreticulin at cell surface in vitro and demonstrated its efficacy as a vaccine in vivo. Remarkably, even at a low concentration (0.5 mg/kg), QAPHA achieved complete tumor regression in approximately 60% of mice treated intratumorally, establishing a long-lasting anticancer immune response. Additionally, QAPHA treatment promoted the infiltration of M1-polarized macrophages in treated mice, indicating the induction of a pro-inflammatory environment within the tumor. Very interestingly, our findings also revealed that QAPHA upregulated major histocompatibility complex class II (MHC-II) expression on TC-1 tumor cells both in vitro and in vivo, facilitating the recruitment of cytotoxic CD4+T cells (CD4+CTL) expressing CD4+, NKG2D+, CRTAM+, and Perforin+. Finally, we showed that tumor regression strongly correlates to MHC-II expression level on tumor cell and CD4+ CTL infiltrate.\n\nCollectively, our findings shed light on the discovery of a new multitarget inhibitor able to induce ICD and MHC-II upregulation in TC-1 tumor cell. These two processes participate in enhancing a specific CD4+ cytotoxic T cell-mediated antitumor response in vivo in our model of lung cancer. This breakthrough suggests the potential of QAPHA as a promising agent for cancer treatment.", "doi": "10.1136/jitc-2023-007588", "pmid": "38609101", "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11015306"}, {"db": "pii", "key": "jitc-2023-007588"}], "notes": [], "created": "2024-07-25T13:12:33.533Z", "modified": "2024-07-25T13:12:33.778Z"}, {"entity": "publication", "iuid": "3f9e00dcad1b4d0780de93789c2d712c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3f9e00dcad1b4d0780de93789c2d712c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3f9e00dcad1b4d0780de93789c2d712c"}}, "title": "Ultralight Ultrafast Enzymes.", "authors": [{"family": "Zhang", "given": "Xuepei", "initials": "X"}, {"family": "Meng", "given": "Zhaowei", "initials": "Z"}, {"family": "Beusch", "given": "Christian M", "initials": "CM"}, {"family": "Gharibi", "given": "Hassan", "initials": "H"}, {"family": "Cheng", "given": "Qing", "initials": "Q"}, {"family": "Lyu", "given": "Hezheng", "initials": "H"}, {"family": "Di Stefano", "given": "Luciano", "initials": "L"}, {"family": "Wang", "given": "Jijing", "initials": "J"}, {"family": "Saei", "given": "Amir A", "initials": "AA"}, {"family": "V\u00e9gv\u00e1ri", "given": "\u00c1kos", "initials": "\u00c1"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "journal article", "published": "2024-01-15", "journal": {"title": "Angew. Chem. Int. Ed. Engl.", "issn": "1521-3773", "issn-l": "1433-7851", "volume": "63", "issue": "3", "pages": "e202316488"}, "abstract": "Inorganic materials depleted of heavy stable isotopes are known to deviate strongly in some physicochemical properties from their isotopically natural counterparts. Here we explored for the first time the effect of simultaneous depletion of the heavy carbon, hydrogen, oxygen and nitrogen isotopes on the bacterium E. coli and the enzymes expressed in it. Bacteria showed faster growth, with most proteins exhibiting higher thermal stability, while for recombinant enzymes expressed in depleted media, faster kinetics was discovered. At room temperature, luciferase, thioredoxin and dihydrofolate reductase and Pfu DNA polymerase showed up to a 250 % increase in activity compared to the native counterparts, with an additional \u223c50 % increase at 10 \u00b0C. Diminished conformational and vibrational entropy is hypothesized to be the cause of the accelerated kinetics. Ultralight enzymes may find an application where extreme reaction rates are required.", "doi": "10.1002/anie.202316488", "pmid": "38009610", "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [], "notes": [], "created": "2023-12-03T20:27:00.593Z", "modified": "2024-08-21T16:03:08.108Z"}, {"entity": "publication", "iuid": "00072a8a51be485d8561ad051125f9ff", "links": {"self": {"href": "https://publications.scilifelab.se/publication/00072a8a51be485d8561ad051125f9ff.json"}, "display": {"href": "https://publications.scilifelab.se/publication/00072a8a51be485d8561ad051125f9ff"}}, "title": "Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis.", "authors": [{"family": "Hung", "given": "Sze Wan", "initials": "SW", "orcid": "0000-0003-0576-4707", "researcher": {"href": "https://publications.scilifelab.se/researcher/e266327d66194491bd01d35d15e998e8.json"}}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M"}, {"family": "Li", "given": "Yiran", "initials": "Y"}, {"family": "Tan", "given": "Zhouyurong", "initials": "Z"}, {"family": "Zheng", "given": "Xu", "initials": "X"}, {"family": "Zhang", "given": "Ruizhe", "initials": "R"}, {"family": "Ding", "given": "Yang", "initials": "Y"}, {"family": "Man", "given": "Gene Chi Wai", "initials": "GCW"}, {"family": "Zhang", "given": "Tao", "initials": "T", "orcid": "0000-0002-8644-8468", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b42e387dd2d4794a3251fc36b41edd3.json"}}, {"family": "Song", "given": "Yi", "initials": "Y"}, {"family": "Wang", "given": "Yao", "initials": "Y", "orcid": "0000-0003-0010-2819", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef1a16171ea94d0e91bdc7b3be0b8493.json"}}, {"family": "Chung", "given": "Jacqueline Pui Wah", "initials": "JPW"}, {"family": "Chan", "given": "Tak Hang", "initials": "TH"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA"}, {"family": "Wang", "given": "Chi Chiu", "initials": "CC", "orcid": "0000-0002-3928-7278", "researcher": {"href": "https://publications.scilifelab.se/researcher/0991744c64d64ffcbc9576d59f9b2bb4.json"}}], "type": "journal article", "published": "2024-01-00", "journal": {"title": "J Pharm Anal", "issn": "2214-0883", "issn-l": null, "volume": "14", "issue": "1", "pages": "100-114"}, "abstract": "Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus. Angiogenesis is a major pathophysiology in endometriosis. Our previous studies have demonstrated that the prodrug of epigallocatechin gallate (ProEGCG) exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate (EGCG). However, their direct binding targets and underlying mechanisms for the differential effects remain unknown. In this study, we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis. Additionally, 1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin (MTDH) and PX domain containing serine/threonine kinase-like (PXK) as novel binding targets of EGCG and ProEGCG, respectively. Computational simulation and BioLayer interferometry were used to confirm their binding affinity. Our results showed that MTDH-EGCG inhibited protein kinase B (Akt)-mediated angiogenesis, while PXK-ProEGCG inhibited epidermal growth factor (EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor (HIF-1a)/vascular endothelial growth factor (VEGF) pathway. In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways. Moreover, our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.", "doi": "10.1016/j.jpha.2023.09.005", "pmid": "38352946", "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10859541"}, {"db": "pii", "key": "S2095-1779(23)00217-4"}], "notes": [], "created": "2023-09-19T18:18:23.893Z", "modified": "2024-08-21T16:03:31.307Z"}, {"entity": "publication", "iuid": "73b9af32e38543cba8ac15a4d1d9f5e6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/73b9af32e38543cba8ac15a4d1d9f5e6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/73b9af32e38543cba8ac15a4d1d9f5e6"}}, "title": "Chemogenetic inhibition of IST1-CHMP1B interaction impairs endosomal recycling and promotes unconventional LC3 lipidation at stalled endosomes", "authors": [{"family": "Knyazeva", "given": "Anastasia", "initials": "A", "orcid": "0000-0001-8504-9126", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a35aa837d114bbc9cab91622d1d7e13.json"}}, {"family": "Li", "given": "Shuang", "initials": "S"}, {"family": "Corkery", "given": "Dale P", "initials": "DP", "orcid": "0000-0001-7930-0134", "researcher": {"href": "https://publications.scilifelab.se/researcher/42e668ad5ea8458b8d0eebc3c653a62e.json"}}, {"family": "Shankar", "given": "Kasturika", "initials": "K", "orcid": "0000-0002-0011-3756", "researcher": {"href": "https://publications.scilifelab.se/researcher/4487e20554dc47688cd5d930c2ca1f74.json"}}, {"family": "Herzog", "given": "Laura K", "initials": "LK", "orcid": "0000-0002-3322-7864", "researcher": {"href": "https://publications.scilifelab.se/researcher/b1e8cfcb24a144d196251f02ab95db4d.json"}}, {"family": "Zhang", "given": "Xuepei", "initials": "X", "orcid": "0000-0001-8304-8437", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8a70e282ff2484d8acd3daa84c480b4.json"}}, {"family": "Singh", "given": "Birendra", "initials": "B", "orcid": "0000-0002-7246-1442", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a37eae28b0b45678502b7be34dbae99.json"}}, {"family": "Niggemeyer", "given": "Georg", "initials": "G"}, {"family": "Grill", "given": "David", "initials": "D"}, {"family": "Gilthorpe", "given": "Jonathan D", "initials": "JD", "orcid": "0000-0002-6884-4774", "researcher": {"href": "https://publications.scilifelab.se/researcher/7eb2a4f38fdc4e0db2516a17d9abdf06.json"}}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Carlson", "given": "Lars Anders", "initials": "LA", "orcid": "0000-0003-2342-6488", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba0e366ce21e49b48212bbed5a0a7bd1.json"}}, {"family": "Waldmann", "given": "Herbert", "initials": "H", "orcid": "0000-0002-9606-7247", "researcher": {"href": "https://publications.scilifelab.se/researcher/54124c0b6aaa4711ab41a2492264fd9a.json"}}, {"family": "Wu", "given": "Yao Wen", "initials": "YW", "orcid": "0000-0002-2573-8736", "researcher": {"href": "https://publications.scilifelab.se/researcher/d7fe2a390f534022b4e9a85f986747c7.json"}}], "type": "posted-content", "published": "2023-08-28", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2023.08.28.555152", "pmid": null, "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [], "notes": [], "created": "2023-12-11T16:34:09.210Z", "modified": "2025-12-18T19:46:51.120Z"}, {"entity": "publication", "iuid": "2f3d05e326e7439481463ab2e3aaf46d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2f3d05e326e7439481463ab2e3aaf46d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2f3d05e326e7439481463ab2e3aaf46d"}}, "title": "Proteome integral solubility alteration high-throughput proteomics assay identifies Collectin-12 as a non-apoptotic microglial caspase-3 substrate.", "authors": [{"family": "Grabert", "given": "Kathleen", "initials": "K", "orcid": "0000-0002-5628-9400", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8fa8c2094cb43f98b5466cf977c307f.json"}}, {"family": "Engskog-Vlachos", "given": "Pinelopi", "initials": "P"}, {"family": "\u0160kand\u00edk", "given": "Martin", "initials": "M"}, {"family": "Vazquez-Cabrera", "given": "Guillermo", "initials": "G"}, {"family": "Murgoci", "given": "Adriana-Natalia", "initials": "A"}, {"family": "Keane", "given": "Lily", "initials": "L", "orcid": "0000-0001-7418-3434", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe6e0fb3bd7347bcb1f2464be431c66d.json"}}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Joseph", "given": "Bertrand", "initials": "B", "orcid": "0000-0001-5655-9979", "researcher": {"href": "https://publications.scilifelab.se/researcher/4cbb8902d726446fa0a3b25b649f82aa.json"}}, {"family": "Cheray", "given": "Mathilde", "initials": "M", "orcid": "0000-0002-7551-6357", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0f0d5fdd40b4113a4fb3222107d4dc9.json"}}], "type": "journal article", "published": "2023-03-11", "journal": {"title": "Cell Death Dis", "issn": "2041-4889", "issn-l": "2041-4889", "volume": "14", "issue": "3", "pages": "192"}, "abstract": "Caspases are a family of proteins mostly known for their role in the activation of the apoptotic pathway leading to cell death. In the last decade, caspases have been found to fulfill other tasks regulating the cell phenotype independently to cell death. Microglia are the immune cells of the brain responsible for the maintenance of physiological brain functions but can also be involved in disease progression when overactivated. We have previously described non-apoptotic roles of caspase-3 (CASP3) in the regulation of the inflammatory phenotype of microglial cells or pro-tumoral activation in the context of brain tumors. CASP3 can regulate protein functions by cleavage of their target and therefore could have multiple substrates. So far, identification of CASP3 substrates has been performed mostly in apoptotic conditions where CASP3 activity is highly upregulated and these approaches do not have the capacity to uncover CASP3 substrates at the physiological level. In our study, we aim at discovering novel substrates of CASP3 involved in the normal regulation of the cell. We used an unconventional approach by chemically reducing the basal level CASP3-like activity (by DEVD-fmk treatment) coupled to a Mass Spectrometry screen (PISA) to identify proteins with different soluble amounts, and consequently, non-cleaved proteins in microglia cells. PISA assay identified several proteins with significant change in their solubility after DEVD-fmk treatment, including a few already known CASP3 substrates which validated our approach. Among them, we focused on the Collectin-12 (COLEC12 or CL-P1) transmembrane receptor and uncovered a potential role for CASP3 cleavage of COLEC12 in the regulation of the phagocytic capacity of microglial cells. Taken together, these findings suggest a new way to uncover non-apoptotic substrates of CASP3 important for the modulation of microglia cell physiology.", "doi": "10.1038/s41419-023-05714-2", "pmid": "36906641", "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10008626"}, {"db": "pii", "key": "10.1038/s41419-023-05714-2"}], "notes": [], "created": "2023-09-19T16:23:03.453Z", "modified": "2024-01-18T23:27:09.612Z"}, {"entity": "publication", "iuid": "fb7b1365091f42f6b512e2669e8f5a93", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fb7b1365091f42f6b512e2669e8f5a93.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fb7b1365091f42f6b512e2669e8f5a93"}}, "title": "NCF1-dependent production of ROS protects against lupus by regulating plasmacytoid dendritic cell development and functions.", "authors": [{"family": "Luo", "given": "Huqiao", "initials": "H"}, {"family": "Urbonaviciute", "given": "Vilma", "initials": "V"}, {"family": "Saei", "given": "Amir Ata", "initials": "AA"}, {"family": "Lyu", "given": "Hezheng", "initials": "H"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M"}, {"family": "V\u00e9gv\u00e1ri", "given": "\u00c1kos", "initials": "\u00c1"}, {"family": "Li", "given": "Yanpeng", "initials": "Y"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA"}, {"family": "Holmdahl", "given": "Rikard", "initials": "R"}], "type": "journal article", "published": "2023-02-28", "journal": {"title": "JCI Insight", "issn": "2379-3708", "issn-l": "2379-3708", "volume": null, "issue": null, "pages": null}, "abstract": "Low capacity to produce reactive oxygen species (ROS) due to mutations in neutrophil cytosolic factor 1 (NCF1/p47phox), a component of NADPH oxidase 2 (NOX2) complex, is strongly associated with systemic lupus erythematosus in both humans and mouse models. Here, we aim to identify the key immune cell type(s) and cellular mechanisms driving lupus pathogenesis under the condition of NCF1-dependent ROS deficiency. Using a set of cell-specific Cre-deleter, the human NCF1-339 variant knock-in, and transgenic mouse strains, we show that low ROS production in plasmacytoid dendritic cells (pDCs) exacerbates both pristane-induced lupus and a newly established Yaa-related spontaneous model by promoting pDC accumulation in multiple organs during lupus development, accompanied by elevated IFN\u03b1 levels and expression of IFN-stimulated genes. Mechanistic studies reveal that ROS deficiency enhances pDC generation through the AKT/mTOR pathway and CCR2-mediated migration to tissues, which together with hyperactivation of the redox-sensitive STING/IFN\u03b1/JAK1/STAT1 cascade further augments type I IFN responses. More importantly, by suppressing these pathways, restoration of NOX2-derived ROS specifically in pDCs protects against lupus. These discoveries explain the causative effect of dysfunctional NCF1 in lupus and demonstrate the protective role of pDC-derived ROS in disease development driven by NCF1-dependent ROS deficiency.", "doi": "10.1172/jci.insight.164875", "pmid": "36853827", "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "164875"}], "notes": [], "created": "2023-03-02T23:59:27.720Z", "modified": "2024-01-18T23:27:43.198Z"}, {"entity": "publication", "iuid": "37a9300e82c9473cae0f25cc17f9098b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/37a9300e82c9473cae0f25cc17f9098b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/37a9300e82c9473cae0f25cc17f9098b"}}, "title": "DAR 16-II Primes Endothelial Cells for Angiogenesis Improving Bone Ingrowth in 3D-Printed BCP Scaffolds and Regeneration of Critically Sized Bone Defects.", "authors": [{"family": "Alfayez", "given": "Eman", "initials": "E"}, {"family": "Veschini", "given": "Lorenzo", "initials": "L"}, {"family": "Dettin", "given": "Monica", "initials": "M", "orcid": "0000-0002-6823-3375", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e294e8555fd4cbf90049c6a650f2300.json"}}, {"family": "Zamuner", "given": "Annj", "initials": "A", "orcid": "0000-0002-8113-0346", "researcher": {"href": "https://publications.scilifelab.se/researcher/e87202eac37f4549ae3e51b50c32d7b3.json"}}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Carreca", "given": "Anna P", "initials": "AP", "orcid": "0000-0002-7389-7555", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a2b667a4f18414ebc95aab655aeb3fd.json"}}, {"family": "Najman", "given": "Stevo", "initials": "S", "orcid": "0000-0002-2411-9802", "researcher": {"href": "https://publications.scilifelab.se/researcher/6bf6151c607a413c8ab93c2aafed6d53.json"}}, {"family": "Ghanaati", "given": "Shahram", "initials": "S", "orcid": "0000-0002-7897-0854", "researcher": {"href": "https://publications.scilifelab.se/researcher/94fdd1f3d5a4403b9ad69abafafde467.json"}}, {"family": "Coward", "given": "Trevor", "initials": "T", "orcid": "0000-0001-7122-7980", "researcher": {"href": "https://publications.scilifelab.se/researcher/b90b1653e9ee4072b2fa83e93adc4cee.json"}}, {"family": "Di Silvio", "given": "Lucy", "initials": "L"}], "type": "journal article", "published": "2022-11-02", "journal": {"title": "Biomolecules", "issn": "2218-273X", "volume": "12", "issue": "11", "pages": "1619", "issn-l": null}, "abstract": "Bone is a highly vascularized tissue and relies on the angiogenesis and response of cells in the immediate environmental niche at the defect site for regeneration. Hence, the ability to control angiogenesis and cellular responses during osteogenesis has important implications in tissue-engineered strategies. Self-assembling ionic-complementary peptides have received much interest as they mimic the natural extracellular matrix. Three-dimensional (3D)-printed biphasic calcium phosphate (BCP) scaffolds coated with self-assembling DAR 16-II peptide provide a support template with the ability to recruit and enhance the adhesion of cells. In vitro studies demonstrated prompt the adhesion of both human umbilical vein endothelial cells (HUVEC) and human mesenchymal stem cells (hMSC), favoring endothelial cell activation toward an angiogenic phenotype. The SEM-EDS and protein micro bicinchoninic acid (BCA) assays demonstrated the efficacy of the coating. Whole proteomic analysis of DAR 16-II-treated HUVECs demonstrated the upregulation of proteins involved in cell adhesion (HABP2), migration (AMOTL1), cytoskeletal re-arrangement (SHC1, TMOD2), immuno-modulation (AMBP, MIF), and morphogenesis (COL4A1). In vivo studies using DAR-16-II-coated scaffolds provided an architectural template, promoting cell colonization, osteogenesis, and angiogenesis. In conclusion, DAR 16-II acts as a proactive angiogenic factor when adsorbed onto BCP scaffolds and provides a simple and effective functionalization step to facilitate the translation of tailored 3D-printed BCP scaffolds for clinical applications.", "doi": "10.3390/biom12111619", "pmid": "36358970", "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC9687468"}, {"db": "pii", "key": "biom12111619"}], "notes": [], "created": "2022-11-04T15:05:41.388Z", "modified": "2023-06-02T10:28:30.814Z"}, {"entity": "publication", "iuid": "092721420219497fb5b3fcc48a3a4c39", "links": {"self": {"href": "https://publications.scilifelab.se/publication/092721420219497fb5b3fcc48a3a4c39.json"}, "display": {"href": "https://publications.scilifelab.se/publication/092721420219497fb5b3fcc48a3a4c39"}}, "title": "Proteomics-Compatible Fourier Transform Isotopic Ratio Mass Spectrometry of Polypeptides.", "authors": [{"family": "Gharibi", "given": "Hassan", "initials": "H", "orcid": "0000-0002-3072-4929", "researcher": {"href": "https://publications.scilifelab.se/researcher/b85179acfa7e4916ad40ae478d6dcc0a.json"}}, {"family": "Chernobrovkin", "given": "Alexey L", "initials": "AL", "orcid": "0000-0001-7709-0161", "researcher": {"href": "https://publications.scilifelab.se/researcher/d36b29dc4fd44785b36b9baa9e291757.json"}}, {"family": "Saei", "given": "Amir Ata", "initials": "AA", "orcid": "0000-0002-2639-6328", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1694ffdcd94a55b6c172a854706e0f.json"}}, {"family": "Zhang", "given": "Xuepei", "initials": "X"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Makarov", "given": "Alexander A", "initials": "AA", "orcid": "0000-0002-7046-6709", "researcher": {"href": "https://publications.scilifelab.se/researcher/f086570824f64f7c927ad4e300622ca2.json"}}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "journal article", "published": "2022-11-01", "journal": {"title": "Anal. Chem.", "issn": "1520-6882", "issn-l": "0003-2700", "volume": "94", "issue": "43", "pages": "15048-15056"}, "abstract": "Measuring the relative abundances of heavy stable isotopes of the elements C, H, N, and O in proteins is of interest in environmental science, archeology, zoology, medicine, and other fields. The isotopic abundance measurements of the fine structure of immonium ions with ultrahigh resolution mass spectrometry obtained in gas-phase fragmentation of polypeptides have previously uncovered anomalous deuterium enrichment in (hydroxy)proline of bone collagen in marine mammals. Here, we provide a detailed description and validation of this approach and demonstrate per mil-range precision of isotopic ratio measurements in aliphatic residues from proteins and cell lysates. The analysis consists of proteomics-type experiment demanding sub-microgram amounts of a protein sample and providing concomitantly protein sequence data allowing one to verify sample purity and establish its identity. A novel software tool protein amino acid-resolved isotopic ratio mass spectrometry (PAIR-MS) is presented for extracting isotopic ratio data from the raw data files acquired on an Orbitrap mass spectrometer.", "doi": "10.1021/acs.analchem.2c03119", "pmid": "36251694", "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [], "notes": [], "created": "2022-11-04T15:02:10.225Z", "modified": "2024-01-18T23:30:37.425Z"}, {"entity": "publication", "iuid": "c23f193faa974137a510630b605f1aa8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c23f193faa974137a510630b605f1aa8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c23f193faa974137a510630b605f1aa8"}}, "title": "Proteome Integral Solubility Alteration (PISA) for High-Throughput Ligand Target Deconvolution with Increased Statistical Significance and Reduced Sample Amount.", "authors": [{"family": "Gaetani", "given": "Massimiliano", "initials": "M"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA"}], "type": "journal article", "published": "2022-10-01", "journal": {"title": "Methods Mol. Biol.", "issn": "1940-6029", "issn-l": "1064-3745", "volume": "2554", "issue": null, "pages": "91-106"}, "abstract": "Proteome Integral Solubility Alteration (PISA) is a recently developed mass spectrometry-based, deep proteomics method for unbiased, proteome-wide target deconvolution of ligands, requiring no chemical ligand modification. PISA can be applied to living cells for studying target engagement in vivo or alternatively to protein extracts to identify in vitro ligand-interacting proteins. Here we describe the PISA workflow optimized in our lab. PISA improves the target discovery throughput 10-100 folds compared to the previously used proteomics methods and provides higher statistical significance for target candidates by enabling several biological replicates. Sample multiplexing makes all-in-one analysis of multiple ligands simultaneously possible. PISA dramatically reduces analysis costs, allowing many research questions in need of target deconvolution to be addressed, and unlocks the potential of miniaturizing biological models, including primary cells.", "doi": "10.1007/978-1-0716-2624-5_7", "pmid": "36178622", "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [], "notes": [], "created": "2022-10-20T17:29:58.792Z", "modified": "2022-11-04T15:03:23.473Z"}, {"entity": "publication", "iuid": "6978cc74d9584c42a41d0f3bb5c79dea", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6978cc74d9584c42a41d0f3bb5c79dea.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6978cc74d9584c42a41d0f3bb5c79dea"}}, "title": "Mapping the GALNT1 substrate landscape with versatile proteomics tools", "authors": [{"family": "Saei", "given": "Amir Ata", "initials": "AA", "orcid": "0000-0002-2639-6328", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1694ffdcd94a55b6c172a854706e0f.json"}}, {"family": "Lundstr\u00f6m", "given": "Susanna L", "initials": "SL", "orcid": "0000-0003-2363-4287", "researcher": {"href": "https://publications.scilifelab.se/researcher/916e190e150e465c9e6afc11911bae04.json"}}, {"family": "Lyu", "given": "Hezheng", "initials": "H", "orcid": "0009-0008-7995-6473", "researcher": {"href": "https://publications.scilifelab.se/researcher/de932cbcb2c341f7a6544104026c7b1c.json"}}, {"family": "Gharibi", "given": "Hassan", "initials": "H", "orcid": "0000-0002-3072-4929", "researcher": {"href": "https://publications.scilifelab.se/researcher/b85179acfa7e4916ad40ae478d6dcc0a.json"}}, {"family": "Lu", "given": "Weiqi", "initials": "W"}, {"family": "Fang", "given": "Pan", "initials": "P"}, {"family": "Zhang", "given": "Xuepei", "initials": "X"}, {"family": "Meng", "given": "Zhaowei", "initials": "Z", "orcid": "0000-0002-7721-2795", "researcher": {"href": "https://publications.scilifelab.se/researcher/60b3f220ebf947779d4b2638d2ccef1c.json"}}, {"family": "Wang", "given": "Jijing", "initials": "J"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M"}, {"family": "V\u00e9gv\u00e1ri", "given": "\u00c1kos", "initials": "\u00c1", "orcid": "0000-0002-1287-0906", "researcher": {"href": "https://publications.scilifelab.se/researcher/74be6e7c877e4f0da6c7ed3747f3ef9d.json"}}, {"family": "Gygi", "given": "Steven P", "initials": "SP", "orcid": "0000-0001-7626-0034", "researcher": {"href": "https://publications.scilifelab.se/researcher/c7237a4242ad47d795a1a2741f32071f.json"}}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "posted-content", "published": "2022-08-24", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2022.08.24.505189", "pmid": null, "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [], "notes": [], "created": "2022-11-29T20:07:08.693Z", "modified": "2025-12-18T18:23:30.185Z"}, {"entity": "publication", "iuid": "6d157a79912f4674b1862a7005ea45ed", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6d157a79912f4674b1862a7005ea45ed.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6d157a79912f4674b1862a7005ea45ed"}}, "title": "Ultrafast and selective labeling of endogenous proteins using affinity-based benzotriazole chemistry.", "authors": [{"family": "Xin", "given": "Xiaoyi", "initials": "X"}, {"family": "Zhang", "given": "Yu", "initials": "Y"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M"}, {"family": "Lundstr\u00f6m", "given": "Susanna L", "initials": "SL"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA"}, {"family": "Zhou", "given": "Yuan", "initials": "Y"}, {"family": "Corkery", "given": "Dale P", "initials": "DP"}, {"family": "Wu", "given": "Yao-Wen", "initials": "Y"}], "type": "journal article", "published": "2022-06-22", "journal": {"title": "Chem. Sci.", "issn": "2041-6520", "issn-l": null, "volume": "13", "issue": "24", "pages": "7240-7246"}, "abstract": "Chemical modification of proteins is enormously useful for characterizing protein function in complex biological systems and for drug development. Selective labeling of native or endogenous proteins is challenging owing to the existence of distinct functional groups in proteins and in living systems. Chemistry for rapid and selective labeling of proteins remains in high demand. Here we have developed novel affinity labeling probes using benzotriazole (BTA) chemistry. We showed that affinity-based BTA probes selectively and covalently label a lysine residue in the vicinity of the ligand binding site of a target protein with a reaction half-time of 28 s. The reaction rate constant is comparable to the fastest biorthogonal chemistry. This approach was used to selectively label different cytosolic and membrane proteins in vitro and in live cells. BTA chemistry could be widely useful for labeling of native/endogenous proteins, target identification and development of covalent inhibitors.", "doi": "10.1039/d1sc05974b", "pmid": "35799822", "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "d1sc05974b"}, {"db": "pmc", "key": "PMC9214888"}], "notes": [], "created": "2021-11-30T12:51:15.281Z", "modified": "2024-01-18T23:31:12.649Z"}, {"entity": "publication", "iuid": "3faa49c2fd47420e8ad82ec59836faea", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3faa49c2fd47420e8ad82ec59836faea.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3faa49c2fd47420e8ad82ec59836faea"}}, "title": "Hepatocyte Thorns, A Novel Drug-Induced Stress Response in Human and Mouse Liver Spheroids.", "authors": [{"family": "Pridgeon", "given": "Chris S", "initials": "CS", "orcid": "0000-0003-4414-8544", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef4e848f8a82437792fcd073268388c7.json"}}, {"family": "Bolhuis", "given": "Dian P", "initials": "DP", "orcid": "0000-0003-3862-8621", "researcher": {"href": "https://publications.scilifelab.se/researcher/18f838548b224467af8a0b6e1527002e.json"}}, {"family": "Milosavljevi\u0107", "given": "Filip", "initials": "F"}, {"family": "Manojlovi\u0107", "given": "Marina", "initials": "M"}, {"family": "V\u00e9gv\u00e1ri", "given": "\u00c1kos", "initials": "\u00c1", "orcid": "0000-0002-1287-0906", "researcher": {"href": "https://publications.scilifelab.se/researcher/74be6e7c877e4f0da6c7ed3747f3ef9d.json"}}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M"}, {"family": "Juki\u0107", "given": "Marin M", "initials": "MM"}, {"family": "Ingelman-Sundberg", "given": "Magnus", "initials": "M", "orcid": "0000-0002-7255-9079", "researcher": {"href": "https://publications.scilifelab.se/researcher/3095e3b59e4b4f5bb2b74332b4423ab3.json"}}], "type": "journal article", "published": "2022-05-10", "journal": {"title": "Cells", "issn": "2073-4409", "issn-l": "2073-4409", "volume": "11", "issue": "10", "pages": null}, "abstract": "The in vivo-relevant phenotype of 3D liver spheroids allows for long-term studies of, e.g., novel mechanisms of chronic drug-induced liver toxicity. Using this system, we present a novel drug-induced stress response in human and murine hepatocyte spheroids, wherein long slender filaments form after chronic treatment with four different drugs, of which three are PPAR\u03b1 antagonists. The morphology of the thorns varies between donors and the compounds used. They are mainly composed of diverse protein fibres, which are glycosylated. Their formation is inhibited by treatment with fatty acids or antioxidants. Treatment of mice with GW6471 revealed changes in gene and protein expression, such as those in the spheroids. In addition, similar changes in keratin expression were seen following the treatment of hepatotoxic drugs, including aflatoxin B1, paracetamol, chlorpromazine, cyclosporine, and ketoconazole. We suggest that thorn formation may be indicative of hepatocyte metaplasia in response to toxicity and that more focus should be placed on alterations of ECM-derived protein expression as biomarkers of liver disease and chronic drug-induced hepatotoxicity, changes that can be studied in stable in vivo-like hepatic cell systems, such as the spheroids.", "doi": "10.3390/cells11101597", "pmid": "35626634", "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "cells11101597"}, {"db": "pmc", "key": "PMC9139950"}], "notes": [], "created": "2022-06-05T20:29:22.197Z", "modified": "2024-01-18T23:31:39.077Z"}, {"entity": "publication", "iuid": "e51cc4ad20614595b24ca51fea3eb883", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e51cc4ad20614595b24ca51fea3eb883.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e51cc4ad20614595b24ca51fea3eb883"}}, "title": "The antimicrobial drug pyrimethamine inhibits STAT3 transcriptional activity by targeting the enzyme dihydrofolate reductase.", "authors": [{"family": "Heppler", "given": "Lisa N", "initials": "LN"}, {"family": "Attarha", "given": "Sanaz", "initials": "S"}, {"family": "Persaud", "given": "Rosanne", "initials": "R"}, {"family": "Brown", "given": "Jennifer I", "initials": "JI"}, {"family": "Wang", "given": "Peng", "initials": "P"}, {"family": "Petrova", "given": "Boryana", "initials": "B"}, {"family": "To\u0161i\u0107", "given": "Isidora", "initials": "I"}, {"family": "Burton", "given": "Foster B", "initials": "FB"}, {"family": "Flamand", "given": "Yael", "initials": "Y"}, {"family": "Walker", "given": "Sarah R", "initials": "SR"}, {"family": "Yeh", "given": "Jennifer E", "initials": "JE"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M"}, {"family": "Kanarek", "given": "Naama", "initials": "N"}, {"family": "Page", "given": "Brent D G", "initials": "BDG"}, {"family": "Frank", "given": "David A", "initials": "DA"}], "type": "journal article", "published": "2022-02-00", "journal": {"title": "J. Biol. Chem.", "issn": "1083-351X", "issn-l": "0021-9258", "volume": "298", "issue": "2", "pages": "101531"}, "abstract": "Cancer is often characterized by aberrant gene expression patterns caused by the inappropriate activation of transcription factors. Signal transducer and activator of transcription 3 (STAT3) is a key transcriptional regulator of many protumorigenic processes and is persistently activated in many types of human cancer. However, like many transcription factors, STAT3 has proven difficult to target clinically. To address this unmet clinical need, we previously developed a cell-based assay of STAT3 transcriptional activity and performed an unbiased and high-throughput screen of small molecules known to be biologically active in humans. We identified the antimicrobial drug pyrimethamine as a novel and specific inhibitor of STAT3 transcriptional activity. Here, we show that pyrimethamine does not significantly affect STAT3 phosphorylation, nuclear translocation, or DNA binding at concentrations sufficient to inhibit STAT3 transcriptional activity, suggesting a potentially novel mechanism of inhibition. To identify the direct molecular target of pyrimethamine and further elucidate the mechanism of action, we used a new quantitative proteome profiling approach called proteome integral solubility alteration coupled with a metabolomic analysis. We identified human dihydrofolate reductase as a target of pyrimethamine and demonstrated that the STAT3-inhibitory effects of pyrimethamine are the result of a deficiency in reduced folate downstream of dihydrofolate reductase inhibition, implicating folate metabolism in the regulation of STAT3 transcriptional activity. This study reveals a previously unknown regulatory node of the STAT3 pathway that may be important for the development of novel strategies to treat STAT3-driven cancers.", "doi": "10.1016/j.jbc.2021.101531", "pmid": "34953855", "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0021-9258(21)01341-7"}, {"db": "pmc", "key": "PMC8800111"}], "notes": [], "created": "2022-01-01T15:15:16.728Z", "modified": "2024-01-18T23:31:55.905Z"}, {"entity": "publication", "iuid": "3b1f4711d7124d40a3fadd57a9a54c5f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3b1f4711d7124d40a3fadd57a9a54c5f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3b1f4711d7124d40a3fadd57a9a54c5f"}}, "title": "Proteome Integral Solubility Alteration (PISA) Assay in Mammalian Cells for Deep, High-Confidence, and High-Throughput Target Deconvolution", "authors": [{"family": "Zhang", "given": "Xuepei", "initials": "X"}, {"family": "Lytovchenko", "given": "Olga", "initials": "O"}, {"family": "Lundstr\u00f6m", "given": "Susanna", "initials": "S"}, {"family": "Zubarev", "given": "Roman", "initials": "R"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M"}], "type": "journal-article", "published": "2022-00-00", "journal": {"title": "BIO-PROTOCOL", "issn": "2331-8325", "issn-l": null, "volume": "12", "issue": "22", "pages": null}, "abstract": null, "doi": "10.21769/bioprotoc.4556", "pmid": "36532690", "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [], "notes": [], "created": "2022-11-21T17:14:58.671Z", "modified": "2023-06-19T13:30:15.569Z"}, {"entity": "publication", "iuid": "9549996dd13046b4bd9b59646e09b7c3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9549996dd13046b4bd9b59646e09b7c3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9549996dd13046b4bd9b59646e09b7c3"}}, "title": "Proteome Integral Solubility Alteration (PISA) for High-Throughput Ligand Target Deconvolution with Increased Statistical Significance and Reduced Sample Amount (Book chapter)", "authors": [{"family": "Gaetani_M_and_Zubarev_RA", "given": "", "initials": ""}], "type": null, "published": "2021-12-09", "journal": {"title": "Methods in Molecular Biology", "issn": "1940-6029", "issn-l": "1064-3745", "volume": "in press", "issue": null, "pages": null}, "abstract": null, "doi": null, "pmid": null, "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [], "notes": [], "created": "2021-12-09T09:49:22.089Z", "modified": "2021-12-09T09:55:07.203Z"}, {"entity": "publication", "iuid": "f150e8e23a9a403d8ed0d635081a5292", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f150e8e23a9a403d8ed0d635081a5292.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f150e8e23a9a403d8ed0d635081a5292"}}, "title": "An integrative proteomics method identifies a regulator of translation during stem cell maintenance and differentiation.", "authors": [{"family": "Sabatier", "given": "Pierre", "initials": "P", "orcid": "0000-0002-2734-1791", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a75556311084e2b827ab1f646d7a16c.json"}}, {"family": "Beusch", "given": "Christian M", "initials": "CM", "orcid": "0000-0001-9100-8283", "researcher": {"href": "https://publications.scilifelab.se/researcher/278e50b11a3c4ef69b6e2708f99b5f3e.json"}}, {"family": "Saei", "given": "Amir A", "initials": "AA", "orcid": "0000-0002-2639-6328", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1694ffdcd94a55b6c172a854706e0f.json"}}, {"family": "Aoun", "given": "Mike", "initials": "M"}, {"family": "Moruzzi", "given": "Noah", "initials": "N"}, {"family": "Coelho", "given": "Ana", "initials": "A"}, {"family": "Leijten", "given": "Niels", "initials": "N", "orcid": "0000-0002-7305-7249", "researcher": {"href": "https://publications.scilifelab.se/researcher/52533fb586904f1598abab4fe93c8b8f.json"}}, {"family": "Nordenskj\u00f6ld", "given": "Magnus", "initials": "M"}, {"family": "Micke", "given": "Patrick", "initials": "P", "orcid": "0000-0003-1210-5961", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc0cba74e74a4c39a8f96319cb9a3034.json"}}, {"family": "Maltseva", "given": "Diana", "initials": "D", "orcid": "0000-0002-4960-5348", "researcher": {"href": "https://publications.scilifelab.se/researcher/4091fbe97bf84c76b279377cb71f61e9.json"}}, {"family": "Tonevitsky", "given": "Alexander G", "initials": "AG"}, {"family": "Millischer", "given": "Vincent", "initials": "V"}, {"family": "Carlos Villaescusa", "given": "J", "initials": "J"}, {"family": "Kadekar", "given": "Sandeep", "initials": "S"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Altynbekova", "given": "Kamilya", "initials": "K"}, {"family": "Kel", "given": "Alexander", "initials": "A"}, {"family": "Berggren", "given": "Per-Olof", "initials": "P"}, {"family": "Simonson", "given": "Oscar", "initials": "O"}, {"family": "Grinnemo", "given": "Karl-Henrik", "initials": "K"}, {"family": "Holmdahl", "given": "Rikard", "initials": "R", "orcid": "0000-0002-4969-2576", "researcher": {"href": "https://publications.scilifelab.se/researcher/49e60d22dd1a4dd1a4ca5a50d9fc4fc7.json"}}, {"family": "Rodin", "given": "Sergey", "initials": "S", "orcid": "0000-0002-6954-1986", "researcher": {"href": "https://publications.scilifelab.se/researcher/2371c1f6b98c46c495530ac860a2beb8.json"}}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "journal article", "published": "2021-11-12", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "12", "issue": "1", "pages": "6558"}, "abstract": "Detailed characterization of cell type transitions is essential for cell biology in general and particularly for the development of stem cell-based therapies in regenerative medicine. To systematically study such transitions, we introduce a method that simultaneously measures protein expression and thermal stability changes in cells and provide the web-based visualization tool ProteoTracker. We apply our method to study differences between human pluripotent stem cells and several cell types including their parental cell line and differentiated progeny. We detect alterations of protein properties in numerous cellular pathways and components including ribosome biogenesis and demonstrate that modulation of ribosome maturation through SBDS protein can be helpful for manipulating cell stemness in vitro. Using our integrative proteomics approach and the web-based tool, we uncover a molecular basis for the uncoupling of robust transcription from parsimonious translation in stem cells and propose a method for maintaining pluripotency in vitro.", "doi": "10.1038/s41467-021-26879-4", "pmid": "34772928", "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-021-26879-4"}, {"db": "pmc", "key": "PMC8590018"}], "notes": [], "created": "2021-11-29T17:23:45.777Z", "modified": "2024-01-18T23:36:09.097Z"}, {"entity": "publication", "iuid": "34c177a6bf874180a7803c15a79588ae", "links": {"self": {"href": "https://publications.scilifelab.se/publication/34c177a6bf874180a7803c15a79588ae.json"}, "display": {"href": "https://publications.scilifelab.se/publication/34c177a6bf874180a7803c15a79588ae"}}, "title": "System-wide identification and prioritization of enzyme substrates by thermal analysis.", "authors": [{"family": "Saei", "given": "Amir Ata", "initials": "AA", "orcid": "0000-0002-2639-6328", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1694ffdcd94a55b6c172a854706e0f.json"}}, {"family": "Beusch", "given": "Christian M", "initials": "CM", "orcid": "0000-0001-9100-8283", "researcher": {"href": "https://publications.scilifelab.se/researcher/278e50b11a3c4ef69b6e2708f99b5f3e.json"}}, {"family": "Sabatier", "given": "Pierre", "initials": "P", "orcid": "0000-0002-2734-1791", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a75556311084e2b827ab1f646d7a16c.json"}}, {"family": "Wells", "given": "Juan Astorga", "initials": "JA", "orcid": "0000-0003-1017-8841", "researcher": {"href": "https://publications.scilifelab.se/researcher/14530d9aa03747858976b4889e959fe5.json"}}, {"family": "Gharibi", "given": "Hassan", "initials": "H", "orcid": "0000-0002-3072-4929", "researcher": {"href": "https://publications.scilifelab.se/researcher/b85179acfa7e4916ad40ae478d6dcc0a.json"}}, {"family": "Meng", "given": "Zhaowei", "initials": "Z"}, {"family": "Chernobrovkin", "given": "Alexey", "initials": "A", "orcid": "0000-0001-7709-0161", "researcher": {"href": "https://publications.scilifelab.se/researcher/d36b29dc4fd44785b36b9baa9e291757.json"}}, {"family": "Rodin", "given": "Sergey", "initials": "S"}, {"family": "N\u00e4reoja", "given": "Katja", "initials": "K"}, {"family": "Thorsell", "given": "Ann-Gerd", "initials": "A"}, {"family": "Karlberg", "given": "Tobias", "initials": "T"}, {"family": "Cheng", "given": "Qing", "initials": "Q"}, {"family": "Lundstr\u00f6m", "given": "Susanna L", "initials": "SL"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "V\u00e9gv\u00e1ri", "given": "\u00c1kos", "initials": "\u00c1", "orcid": "0000-0002-1287-0906", "researcher": {"href": "https://publications.scilifelab.se/researcher/74be6e7c877e4f0da6c7ed3747f3ef9d.json"}}, {"family": "Arn\u00e9r", "given": "Elias S J", "initials": "ESJ", "orcid": "0000-0002-4807-6114", "researcher": {"href": "https://publications.scilifelab.se/researcher/70a545effced47da8a5192a7472ceb8f.json"}}, {"family": "Sch\u00fcler", "given": "Herwig", "initials": "H", "orcid": "0000-0003-4059-3501", "researcher": {"href": "https://publications.scilifelab.se/researcher/f49b25ddfc934f3ca41020c3f38c6bfc.json"}}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "journal article", "published": "2021-02-26", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "12", "issue": "1", "pages": "1296"}, "abstract": "Despite the immense importance of enzyme-substrate reactions, there is a lack of general and unbiased tools for identifying and prioritizing substrate proteins that are modified by the enzyme on the structural level. Here we describe a high-throughput unbiased proteomics method called System-wide Identification and prioritization of Enzyme Substrates by Thermal Analysis (SIESTA). The approach assumes that the enzymatic post-translational modification of substrate proteins is likely to change their thermal stability. In our proof-of-concept studies, SIESTA successfully identifies several known and novel substrate candidates for selenoprotein thioredoxin reductase 1, protein kinase B (AKT1) and poly-(ADP-ribose) polymerase-10 systems. Wider application of SIESTA can enhance our understanding of the role of enzymes in homeostasis and disease, opening opportunities to investigate the effect of post-translational modifications on signal transduction and facilitate drug discovery.", "doi": "10.1038/s41467-021-21540-6", "pmid": "33637753", "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-021-21540-6"}, {"db": "pmc", "key": "PMC7910609"}], "notes": [], "created": "2020-01-23T10:41:17.194Z", "modified": "2021-12-09T09:37:12.987Z"}, {"entity": "publication", "iuid": "2d03d3eccf51447f8598cb76587b9f98", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2d03d3eccf51447f8598cb76587b9f98.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2d03d3eccf51447f8598cb76587b9f98"}}, "title": "Capillary leakage provides nutrients and antioxidants for rapid pneumococcal proliferation in influenza-infected lower airways.", "authors": [{"family": "Sender", "given": "Vicky", "initials": "V", "orcid": "0000-0003-2174-946X", "researcher": {"href": "https://publications.scilifelab.se/researcher/806e259d26014318a915ebe132bafb5d.json"}}, {"family": "Hentrich", "given": "Karina", "initials": "K", "orcid": "0000-0001-6660-7233", "researcher": {"href": "https://publications.scilifelab.se/researcher/8dfc3f0078864e68baf26086869ab2d5.json"}}, {"family": "Pathak", "given": "Anuj", "initials": "A"}, {"family": "Tan Qian Ler", "given": "Alicia", "initials": "A", "orcid": "0000-0001-9298-4008", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba872b0c12754f6bb57015ede1d10755.json"}}, {"family": "Embaie", "given": "Bethel Tesfai", "initials": "BT", "orcid": "0000-0002-7081-5032", "researcher": {"href": "https://publications.scilifelab.se/researcher/bc274efbd34147e3972c85858d252a37.json"}}, {"family": "Lundstr\u00f6m", "given": "Susanna L", "initials": "SL"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Bergstrand", "given": "Jan", "initials": "J"}, {"family": "Nakamoto", "given": "Rei", "initials": "R", "orcid": "0000-0001-7807-6548", "researcher": {"href": "https://publications.scilifelab.se/researcher/07fdc7bfbb58498d986542fd1ea2cdce.json"}}, {"family": "Sham", "given": "Lok-To", "initials": "L"}, {"family": "Widengren", "given": "Jerker", "initials": "J"}, {"family": "Normark", "given": "Staffan", "initials": "S", "orcid": "0000-0001-7917-3921", "researcher": {"href": "https://publications.scilifelab.se/researcher/72caf78541474b5bbbc2049facb70954.json"}}, {"family": "Henriques-Normark", "given": "Birgitta", "initials": "B"}], "type": "journal article", "published": "2020-12-08", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "issn-l": "0027-8424", "volume": "117", "issue": "49", "pages": "31386-31397"}, "abstract": "Influenza A virus (IAV)-related mortality is often due to secondary bacterial infections, primarily by pneumococci. Here, we study how IAV-modulated changes in the lungs affect bacterial replication in the lower respiratory tract (LRT). Bronchoalveolar lavages (BALs) from coinfected mice showed rapid bacterial proliferation 4 to 6 h after pneumococcal challenge. Metabolomic and quantitative proteomic analyses demonstrated capillary leakage with efflux of nutrients and antioxidants into the alveolar space. Pneumococcal adaptation to IAV-induced inflammation and redox imbalance increased the expression of the pneumococcal chaperone/protease HtrA. Presence of HtrA resulted in bacterial growth advantage in the IAV-infected LRT and protection from complement-mediated opsonophagocytosis due to capsular production. Absence of HtrA led to growth arrest in vitro that was partially restored by antioxidants. Pneumococcal ability to grow in the IAV-infected LRT depends on the nutrient-rich milieu with increased levels of antioxidants such as ascorbic acid and its ability to adapt to and cope with oxidative damage and immune clearance.", "doi": "10.1073/pnas.2012265117", "pmid": "33229573", "labels": {"Chemical Proteomics": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "2012265117"}, {"db": "pmc", "key": "PMC7733805"}], "notes": [], "created": "2020-11-30T11:01:05.695Z", "modified": "2024-01-18T23:34:47.832Z"}, {"entity": "publication", "iuid": "7d82542687dd4fccb7affffc780d00ec", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7d82542687dd4fccb7affffc780d00ec.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7d82542687dd4fccb7affffc780d00ec"}}, "title": "Lysine-specific demethylase 1A restricts ex vivo propagation of human HSCs and is a target of UM171.", "authors": [{"family": "Subramaniam", "given": "Agatheeswaran", "initials": "A", "orcid": "0000-0003-3966-3875", "researcher": {"href": "https://publications.scilifelab.se/researcher/5ccb1e6798b84f128c3143c8da8bd35a.json"}}, {"family": "\u017demaitis", "given": "Kristijonas", "initials": "K", "orcid": "0000-0002-4098-0184", "researcher": {"href": "https://publications.scilifelab.se/researcher/d122126ea9094e1ab3c83a2265175042.json"}}, {"family": "Talkhoncheh", "given": "Mehrnaz Safaee", "initials": "MS"}, {"family": "Yudovich", "given": "David", "initials": "D", "orcid": "0000-0002-6580-0637", "researcher": {"href": "https://publications.scilifelab.se/researcher/e88d5ea329514c1881c5be9d9ab14412.json"}}, {"family": "B\u00e4ckstr\u00f6m", "given": "Alexandra", "initials": "A", "orcid": "0000-0003-2926-4221", "researcher": {"href": "https://publications.scilifelab.se/researcher/8032ff5c71544155978bfc1c73b34848.json"}}, {"family": "Debnath", "given": "Shubhranshu", "initials": "S"}, {"family": "Chen", "given": "Jun", "initials": "J", "orcid": "0000-0001-8516-0975", "researcher": {"href": "https://publications.scilifelab.se/researcher/93cf6eaa8a61475789a772d30f29d2e5.json"}}, {"family": "Jain", "given": "Mayur Vilas", "initials": "MV"}, {"family": "Galeev", "given": "Roman", "initials": "R"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}, {"family": "Larsson", "given": "Jonas", "initials": "J"}], "type": "journal article", "published": "2020-11-05", "journal": {"title": "Blood", "issn": "1528-0020", "issn-l": "0006-4971", "volume": "136", "issue": "19", "pages": "2151-2161"}, "abstract": "Culture conditions in which hematopoietic stem cells (HSCs) can be expanded for clinical benefit are highly sought after. Here, we report that inhibition of the epigenetic regulator lysine-specific histone demethylase 1A (LSD1) induces a rapid expansion of human cord blood-derived CD34+ cells and promotes in vitro propagation of long-term repopulating HSCs by preventing differentiation. The phenotype and molecular characteristics of cells treated with LSD1 inhibitors were highly similar to cells treated with UM171, an agent promoting expansion of HSCs through undefined mechanisms and currently being tested in clinical trials. Strikingly, we found that LSD1, as well as other members of the LSD1-containing chromatin remodeling complex CoREST, is rapidly polyubiquitinated and degraded upon UM171 treatment. CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 depletion of the CoREST core member, RCOR1, resulted in expansion of CD34+ cells similar to LSD1 inhibition and UM171. Taken together, LSD1 and CoREST restrict HSC expansion and are principal targets of UM171, forming a mechanistic basis for the HSC-promoting activity of UM171.", "doi": "10.1182/blood.2020005827", "pmid": "32582923", "labels": {"Chemical Proteomics": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S0006-4971(21)00492-4"}, {"db": "pmc", "key": "PMC7645986"}], "notes": [], "created": "2020-07-01T11:45:41.535Z", "modified": "2024-01-18T23:37:23.868Z"}, {"entity": "publication", "iuid": "3d52c9ab12914a419feae20a6e446826", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3d52c9ab12914a419feae20a6e446826.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3d52c9ab12914a419feae20a6e446826"}}, "title": "Thermal Proteome Profiling Identifies Oxidative-Dependent Inhibition of the Transcription of Major Oncogenes as a New Therapeutic Mechanism for Select Anticancer Compounds.", "authors": [{"family": "Peuget", "given": "Sylvain", "initials": "S"}, {"family": "Zhu", "given": "Jiawei", "initials": "J"}, {"family": "Sanz", "given": "Gema", "initials": "G", "orcid": "0000-0002-6227-0431", "researcher": {"href": "https://publications.scilifelab.se/researcher/3353dc98689341b4824217786d1e3956.json"}}, {"family": "Singh", "given": "Madhurendra", "initials": "M"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Chen", "given": "Xinsong", "initials": "X"}, {"family": "Shi", "given": "Yao", "initials": "Y"}, {"family": "Saei", "given": "Amir Ata", "initials": "AA", "orcid": "0000-0002-2639-6328", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1694ffdcd94a55b6c172a854706e0f.json"}}, {"family": "Visnes", "given": "Torkild", "initials": "T", "orcid": "0000-0003-1047-988X", "researcher": {"href": "https://publications.scilifelab.se/researcher/599a0da924424d098adc248b67fabf05.json"}}, {"family": "Lindstr\u00f6m", "given": "Mikael S", "initials": "MS", "orcid": "0000-0003-1148-8497", "researcher": {"href": "https://publications.scilifelab.se/researcher/5aa942fbfbee4257a129b3e7888f5b6d.json"}}, {"family": "Rihani", "given": "Ali", "initials": "A", "orcid": "0000-0002-6176-0519", "researcher": {"href": "https://publications.scilifelab.se/researcher/5dc94d95e8204181bf3e75354ec1678b.json"}}, {"family": "Moyano-Galceran", "given": "Lidia", "initials": "L", "orcid": "0000-0001-9219-6394", "researcher": {"href": "https://publications.scilifelab.se/researcher/085eed2a15bc4be08acbe21a18cb4e6c.json"}}, {"family": "Carlson", "given": "Joseph W", "initials": "JW", "orcid": "0000-0002-3006-4107", "researcher": {"href": "https://publications.scilifelab.se/researcher/cb81cad4b24d4692bc21bda7305f21f1.json"}}, {"family": "Hjerpe", "given": "Elisabet", "initials": "E"}, {"family": "Joneborg", "given": "Ulrika", "initials": "U"}, {"family": "Lehti", "given": "Kaisa", "initials": "K", "orcid": "0000-0001-9110-8719", "researcher": {"href": "https://publications.scilifelab.se/researcher/480c0e2b92df4dccbae3940721525345.json"}}, {"family": "Hartman", "given": "Johan", "initials": "J", "orcid": "0000-0002-6500-8527", "researcher": {"href": "https://publications.scilifelab.se/researcher/da7cefda6e00463d8ba95fc63eeb8f0a.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Zubarev", "given": "Roman", "initials": "R", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}, {"family": "Selivanova", "given": "Galina", "initials": "G"}], "type": "journal article", "published": "2020-04-01", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "issn-l": "0008-5472", "volume": "80", "issue": "7", "pages": "1538-1550"}, "abstract": "Identification of the molecular mechanism of action (MoA) of bioactive compounds is a crucial step for drug development but remains a challenging task despite recent advances in technology. In this study, we applied multidimensional proteomics, sensitivity correlation analysis, and transcriptomics to identify a common MoA for the anticancer compounds RITA, aminoflavone (AF), and oncrasin-1 (Onc-1). Global thermal proteome profiling revealed that the three compounds target mRNA processing and transcription, thereby attacking a cancer vulnerability, transcriptional addiction. This led to the preferential loss of expression of oncogenes involved in PDGF, EGFR, VEGF, insulin/IGF/MAPKK, FGF, Hedgehog, TGF\u03b2, and PI3K signaling pathways. Increased reactive oxygen species level in cancer cells was a prerequisite for targeting the mRNA transcription machinery, thus conferring cancer selectivity to these compounds. Furthermore, DNA repair factors involved in homologous recombination were among the most prominently repressed proteins. In cancer patient samples, RITA, AF, and Onc-1 sensitized to poly(ADP-ribose) polymerase inhibitors both in vitro and ex vivo These findings might pave a way for new synthetic lethal combination therapies.Significance: These findings highlight agents that target transcriptional addiction in cancer cells and suggest combination treatments that target RNA processing and DNA repair pathways simultaneously as effective cancer therapies.", "doi": "10.1158/0008-5472.CAN-19-2069", "pmid": "32019870", "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-19-2069"}], "notes": [], "created": "2020-02-07T22:52:26.989Z", "modified": "2024-01-18T23:48:25.871Z"}, {"entity": "publication", "iuid": "0db4269a42a5414c862b6766046b6288", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0db4269a42a5414c862b6766046b6288.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0db4269a42a5414c862b6766046b6288"}}, "title": "ProTargetMiner as a proteome signature library of anticancer molecules for functional discovery", "authors": [{"family": "Saei", "given": "Amir Ata", "initials": "AA", "orcid": "0000-0002-2639-6328", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1694ffdcd94a55b6c172a854706e0f.json"}}, {"family": "Beusch", "given": "Christian Michel", "initials": "CM", "orcid": "0000-0001-9100-8283", "researcher": {"href": "https://publications.scilifelab.se/researcher/278e50b11a3c4ef69b6e2708f99b5f3e.json"}}, {"family": "Chernobrovkin", "given": "Alexey", "initials": "A", "orcid": "0000-0001-7709-0161", "researcher": {"href": "https://publications.scilifelab.se/researcher/d36b29dc4fd44785b36b9baa9e291757.json"}}, {"family": "Sabatier", "given": "Pierre", "initials": "P", "orcid": "0000-0002-2734-1791", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a75556311084e2b827ab1f646d7a16c.json"}}, {"family": "Zhang", "given": "Bo", "initials": "B", "orcid": "0000-0001-8890-8416", "researcher": {"href": "https://publications.scilifelab.se/researcher/79097385e3ea4496bb498c981302b344.json"}}, {"family": "Tokat", "given": "\u00dclk\u00fc G\u00fcler", "initials": "\u00dcG"}, {"family": "Stergiou", "given": "Eleni", "initials": "E", "orcid": "0000-0001-9115-4985", "researcher": {"href": "https://publications.scilifelab.se/researcher/9ff5335a69db40848ec6131d4735da18.json"}}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "V\u00e9gv\u00e1ri", "given": "\u00c1kos", "initials": "\u00c1", "orcid": "0000-0002-1287-0906", "researcher": {"href": "https://publications.scilifelab.se/researcher/74be6e7c877e4f0da6c7ed3747f3ef9d.json"}}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "journal-article", "published": "2019-12-00", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "10", "issue": "1", "pages": "5715"}, "abstract": "Deconvolution of targets and action mechanisms of anticancer compounds is fundamental in drug development. Here, we report on ProTargetMiner as a publicly available expandable proteome signature library of anticancer molecules in cancer cell lines. Based on 287 A549 adenocarcinoma proteomes affected by 56 compounds, the main dataset contains 7,328 proteins and 1,307,859 refined protein-drug pairs. These proteomic signatures cluster by compound targets and action mechanisms. The targets and mechanistic proteins are deconvoluted by partial least square modeling, provided through the website http://protargetminer.genexplain.com. For 9 molecules representing the most diverse mechanisms and the common cancer cell lines MCF-7, RKO and A549, deep proteome datasets are obtained. Combining data from the three cell lines highlights common drug targets and cell-specific differences. The database can be easily extended and merged with new compound signatures. ProTargetMiner serves as a chemical proteomics resource for the cancer research community, and can become a valuable tool in drug discovery.", "doi": "10.1038/s41467-019-13582-8", "pmid": "31844049", "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-019-13582-8"}, {"db": "pmc", "key": "PMC6915695"}], "notes": [], "created": "2019-01-10T14:09:06.234Z", "modified": "2021-06-21T14:06:27.659Z"}, {"entity": "publication", "iuid": "7f26d8d51b734a3782440cdbd02668b9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7f26d8d51b734a3782440cdbd02668b9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7f26d8d51b734a3782440cdbd02668b9"}}, "title": "Proteome Integral Solubility Alteration: A High-Throughput Proteomics Assay for Target Deconvolution.", "authors": [{"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Sabatier", "given": "Pierre", "initials": "P", "orcid": "0000-0002-2734-1791", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a75556311084e2b827ab1f646d7a16c.json"}}, {"family": "Saei", "given": "Amir A", "initials": "AA"}, {"family": "Beusch", "given": "Christian M", "initials": "CM"}, {"family": "Yang", "given": "Zhe", "initials": "Z"}, {"family": "Lundstr\u00f6m", "given": "Susanna L", "initials": "SL"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "journal article", "published": "2019-11-01", "journal": {"volume": "18", "issn": "1535-3907", "issue": "11", "pages": "4027-4037", "title": "J. Proteome Res.", "issn-l": "1535-3893"}, "abstract": "Various agents, including drugs as well as nonmolecular stimuli, induce alterations in the physicochemical properties of proteins in cell lysates, living cells, and organisms. These alterations can be probed by applying a stability- and solubility-modifying factor, such as elevated temperature, to a varying degree. As a second dimension of variation, drug concentration or agent intensity/concentration can be used. Compared to standard approaches where curves are fitted to protein solubility data acquired at different temperatures and drug concentrations, Proteome Integral Solubility Alteration (PISA) assay increases the analysis throughput by 1 to 2 orders of magnitude for an unlimited number of factor variation points in such a scheme. The consumption of the compound and biological material decreases in PISA by the same factor. We envision widespread use of the PISA approach in chemical biology and drug development.", "doi": "10.1021/acs.jproteome.9b00500", "pmid": "31545609", "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [], "notes": [], "created": "2019-11-29T16:45:34.828Z", "modified": "2021-07-08T08:52:06.553Z"}, {"entity": "publication", "iuid": "2577cf5e197a4ce39380a3cd6f010f78", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2577cf5e197a4ce39380a3cd6f010f78.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2577cf5e197a4ce39380a3cd6f010f78"}}, "title": "Functional Identification of Target by Expression Proteomics ( FITExP )", "authors": [{"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "other", "published": "2019-08-13", "journal": {"title": "ISBN: 9781118969557", "issn": "ISBN: 9781118969557", "issn-l": null, "volume": null, "issue": null, "pages": "257-266"}, "abstract": null, "doi": "10.1002/9781118970195.ch10", "pmid": null, "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [], "notes": [], "created": "2019-12-16T11:30:33.195Z", "modified": "2025-12-18T20:07:36.918Z"}, {"entity": "publication", "iuid": "fc6f26abc9294ff2abf1eeb6b3fb9dd8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fc6f26abc9294ff2abf1eeb6b3fb9dd8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fc6f26abc9294ff2abf1eeb6b3fb9dd8"}}, "title": "SpotLight Proteomics-A IgG-Enrichment Phenotype Profiling Approach with Clinical Implications.", "authors": [{"family": "Lundstr\u00f6m", "given": "Susanna L", "initials": "SL", "orcid": "0000-0003-2363-4287", "researcher": {"href": "https://publications.scilifelab.se/researcher/916e190e150e465c9e6afc11911bae04.json"}}, {"family": "Heyder", "given": "Tina", "initials": "T"}, {"family": "Wiklundh", "given": "Emil", "initials": "E"}, {"family": "Zhang", "given": "Bo", "initials": "B"}, {"family": "Eklund", "given": "Anders", "initials": "A"}, {"family": "Grunewald", "given": "Johan", "initials": "J"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "journal article", "published": "2019-05-01", "journal": {"volume": "20", "issn": "1422-0067", "issue": "9", "pages": "2157", "title": "Int J Mol Sci", "issn-l": null}, "abstract": "Sarcoidosis is a systemic interstitial lung disease of unknown aetiology. Less invasive diagnostics are needed to decipher disease pathology and to distinguish sub-phenotypes. Here we test if SpotLight proteomics, which combines de novo MS/MS sequencing of enriched IgG and co-extracted proteins with subsequent label-free quantification of new and known peptides, can differentiate controls and sarcoidosis phenotypes (L\u00f6fgrens and non-L\u00f6fgrens syndrome, LS and nonLS). Intra-individually matched IgG enriched from serum and bronchial lavage fluid (BALF) from controls (n = 12), LS (n = 11) and nonLS (n = 12) were investigated. High-resolution mass-spectrometry SpotLight proteomics and uni- and multivariate-statistical analyses were used for data processing. Major differences were particularly observed in control-BALF versus sarcoidosis-BALF. However, interestingly, information obtained from BALF profiles was still present (but less prominent) in matched serum profiles. By using information from orthogonal partial least squares discriminant analysis (OPLS-DA) differentiating 1) sarcoidosis-BALF and control-BALF and 2) LS-BALF vs. nonLS-BALF, control-serum and sarcoidosis-serum (p = 0.0007) as well as LS-serum and nonLS-serum (p = 0.006) could be distinguished. Noteworthy, many factors prominent in identifying controls and patients were those associated with Fc-regulation, but also features from the IgG-Fab region and novel peptide variants. Differences between phenotypes were mostly IgG-specificity related. The results support the analytical utility of SpotLight proteomics which prospectively have potential to differentiate closely related phenotypes from a simple blood test.", "doi": "10.3390/ijms20092157", "pmid": "31052352", "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [{"db": "pii", "key": "ijms20092157"}, {"db": "pmc", "key": "PMC6540603"}], "notes": [], "created": "2020-01-23T10:33:23.951Z", "modified": "2021-07-08T08:58:46.881Z"}, {"entity": "publication", "iuid": "1cb24ce38acd44ed832fe09fee558741", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1cb24ce38acd44ed832fe09fee558741.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1cb24ce38acd44ed832fe09fee558741"}}, "title": "Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation.", "authors": [{"family": "Visnes", "given": "Torkild", "initials": "T", "orcid": "0000-0003-1047-988X", "researcher": {"href": "https://publications.scilifelab.se/researcher/599a0da924424d098adc248b67fabf05.json"}}, {"family": "C\u00e1zares-K\u00f6rner", "given": "Armando", "initials": "A", "orcid": "0000-0003-0765-3787", "researcher": {"href": "https://publications.scilifelab.se/researcher/59a3775a65e9430aa96ad72230029236.json"}}, {"family": "Hao", "given": "Wenjing", "initials": "W", "orcid": "0000-0002-8487-5968", "researcher": {"href": "https://publications.scilifelab.se/researcher/44953a42d8b84079af5e600b4a413ef7.json"}}, {"family": "Wallner", "given": "Olov", "initials": "O", "orcid": "0000-0002-6481-237X", "researcher": {"href": "https://publications.scilifelab.se/researcher/83eb2f7ee2f34f2cbacaae2dadcd90e9.json"}}, {"family": "Masuyer", "given": "Geoffrey", "initials": "G", "orcid": "0000-0002-9527-2310", "researcher": {"href": "https://publications.scilifelab.se/researcher/41dcc0806dba4a56bb04725812f3a000.json"}}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O"}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "Sarno", "given": "Antonio", "initials": "A", "orcid": "0000-0002-9308-8018", "researcher": {"href": "https://publications.scilifelab.se/researcher/f47cb410dce04c30bf70b85c6633d72f.json"}}, {"family": "Manoilov", "given": "Aleksandr", "initials": "A"}, {"family": "Astorga-Wells", "given": "Juan", "initials": "J", "orcid": "0000-0003-1017-8841", "researcher": {"href": "https://publications.scilifelab.se/researcher/14530d9aa03747858976b4889e959fe5.json"}}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS"}, {"family": "Pan", "given": "Lang", "initials": "L"}, {"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Karsten", "given": "Stella", "initials": "S", "orcid": "0000-0001-6191-4314", "researcher": {"href": "https://publications.scilifelab.se/researcher/4cbde9247c7145ff8ea0bbc0b0c5c477.json"}}, {"family": "Gokturk", "given": "Camilla", "initials": "C"}, {"family": "Grube", "given": "Maurice", "initials": "M"}, {"family": "Homan", "given": "Evert J", "initials": "EJ"}, {"family": "Hanna", "given": "Bishoy M F", "initials": "BMF", "orcid": "0000-0001-7027-6553", "researcher": {"href": "https://publications.scilifelab.se/researcher/d39737c7b47549e292f1c668a48e2491.json"}}, {"family": "Paulin", "given": "Cynthia B J", "initials": "CBJ", "orcid": "0000-0002-5698-7962", "researcher": {"href": "https://publications.scilifelab.se/researcher/f54dd3938c0640f1b770a3b52baba6d9.json"}}, {"family": "Pham", "given": "Therese", "initials": "T"}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "Berglund", "given": "Ulrika Warpman", "initials": "UW"}, {"family": "von Nicolai", "given": "Catharina", "initials": "C"}, {"family": "Benitez-Buelga", "given": "Carlos", "initials": "C"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Ivanic", "given": "Dag", "initials": "D", "orcid": "0000-0002-6052-2236", "researcher": {"href": "https://publications.scilifelab.se/researcher/aecb0c1aee9f454188e4cbc778afc22e.json"}}, {"family": "Iliev", "given": "Petar", "initials": "P", "orcid": "0000-0002-3905-9814", "researcher": {"href": "https://publications.scilifelab.se/researcher/5235dc5c5406476c958a4048eeef9e6f.json"}}, {"family": "Scobie", "given": "Martin", "initials": "M", "orcid": "0000-0002-7073-8495", "researcher": {"href": "https://publications.scilifelab.se/researcher/87c041a8b3414f5db02873dc8013806b.json"}}, {"family": "Krokan", "given": "Hans E", "initials": "HE"}, {"family": "Baranczewski", "given": "Pawel", "initials": "P"}, {"family": "Artursson", "given": "Per", "initials": "P", "orcid": "0000-0002-3708-7395", "researcher": {"href": "https://publications.scilifelab.se/researcher/31575936c2714e1eb2f35c12df9a65a8.json"}}, {"family": "Altun", "given": "Mikael", "initials": "M"}, {"family": "Jensen", "given": "Annika Jenmalm", "initials": "AJ"}, {"family": "Kalder\u00e9n", "given": "Christina", "initials": "C"}, {"family": "Ba", "given": "Xueqing", "initials": "X", "orcid": "0000-0002-1075-5496", "researcher": {"href": "https://publications.scilifelab.se/researcher/5c547a402d534219905c835930d7a094.json"}}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97eba9f5edf4d76a5259c4baa8366c5.json"}}, {"family": "Boldogh", "given": "Istvan", "initials": "I"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}], "type": "journal article", "published": "2018-11-16", "journal": {"volume": "362", "issn": "1095-9203", "issue": "6416", "pages": "834-839", "title": "Science", "issn-l": "0036-8075"}, "abstract": "The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG and because Ogg1-deficient mice are resistant to acute and systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention and treatment of inflammation. We developed TH5487, a selective active-site inhibitor of OGG1, which hampers OGG1 binding to and repair of 8-oxoG and which is well tolerated by mice. TH5487 prevents tumor necrosis factor-\u03b1-induced OGG1-DNA interactions at guanine-rich promoters of proinflammatory genes. This, in turn, decreases DNA occupancy of nuclear factor \u03baB and proinflammatory gene expression, resulting in decreased immune cell recruitment to mouse lungs. Thus, we present a proof of concept that targeting oxidative DNA repair can alleviate inflammatory conditions in vivo.", "doi": "10.1126/science.aar8048", "pmid": "30442810", "labels": {"Chemical Proteomics": "Collaborative", "Protein Science Facility (PSF)": "Service", "Bioinformatics Support for Computational Resources": "Service", "Chemical Biology Consortium Sweden": "Collaborative", "Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pii", "key": "362/6416/834"}, {"db": "pmc", "key": "PMC6645780"}, {"db": "mid", "key": "NIHMS1026297"}], "notes": [], "created": "2018-11-19T09:35:21.697Z", "modified": "2025-10-17T13:05:08.336Z"}, {"entity": "publication", "iuid": "8f06e3d6cef440cd8b277c7f09af099b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8f06e3d6cef440cd8b277c7f09af099b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8f06e3d6cef440cd8b277c7f09af099b"}}, "title": "STAT3 differential scanning fluorimetry and differential scanning light scattering assays: Addressing a missing link in the characterization of STAT3 inhibitor interactions.", "authors": [{"family": "Desroses", "given": "Matthieu", "initials": "M"}, {"family": "Busker", "given": "Sander", "initials": "S"}, {"family": "Astorga-Wells", "given": "Juan", "initials": "J"}, {"family": "Attarha", "given": "Sanaz", "initials": "S"}, {"family": "Kolosenko", "given": "Iryna", "initials": "I"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Grand\u00e9r", "given": "Dan", "initials": "D"}, {"family": "Page", "given": "Brent D G", "initials": "BDG"}], "type": "journal article", "published": "2018-10-25", "journal": {"volume": "160", "issn": "1873-264X", "issue": null, "pages": "80-88", "title": "Journal of Pharmaceutical and Biomedical Analysis", "issn-l": "0731-7085"}, "abstract": "STAT3 protein is an established target for the development of new cancer therapeutic agents. Despite lacking a traditional binding site for small molecule inhibitors, many STAT3 inhibitors have been identified and explored for their anti-cancer activity. Because STAT3 signaling is mediated by protein-protein interactions, indirect methods are often employed to determine if proposed STAT3 inhibitors bind to STAT3 protein. While established STAT3 inhibition assays (such as the fluorescence polarization assay, electrophoretic mobility shift assay and ELISAs) have been used to identify novel inhibitors of STAT3 signaling, methods that directly assess STAT3 protein-inhibitor interactions could facilitate the development of novel inhibitors. In this context, we herein report new STAT3 binding assays based on differential scanning fluorimetry (DSF) and differential scanning light scattering (DSLS) to characterize interactions between STAT3 protein and inhibitors. Several peptide and small molecule STAT3 inhibitors have been evaluated, and new insight into how these compounds may interact with STAT3 is provided.", "doi": "10.1016/j.jpba.2018.07.018", "pmid": "30086509", "labels": {"Chemical Proteomics": "Collaborative", "Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pii", "key": "S0731-7085(18)30154-7"}], "notes": [], "created": "2018-08-30T11:54:17.344Z", "modified": "2021-07-08T13:01:30.852Z"}, {"entity": "publication", "iuid": "aee194257ec94bb3bae080f4e5720c88", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aee194257ec94bb3bae080f4e5720c88.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aee194257ec94bb3bae080f4e5720c88"}}, "title": "New Promises of Chemical Proteomics for Drug Development", "authors": [{"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": null, "published": "2017-06-27", "journal": {"title": "Novel Approaches in Drug Designing & Development", "issn": "2575-8942", "issn-l": null, "volume": "2", "issue": "1", "pages": "555579"}, "abstract": null, "doi": "10.19080/NAPDD.2017.02.555579", "pmid": null, "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [], "notes": [], "created": "2020-01-08T13:39:38.348Z", "modified": "2024-01-18T23:43:48.969Z"}, {"entity": "publication", "iuid": "24344bb489604ac38a35c61b68e2a68c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/24344bb489604ac38a35c61b68e2a68c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/24344bb489604ac38a35c61b68e2a68c"}}, "title": "SpotLight Proteomics: uncovering the hidden blood proteome improves diagnostic power of proteomics.", "authors": [{"family": "Lundstr\u00f6m", "given": "Susanna L", "initials": "SL"}, {"family": "Zhang", "given": "Bo", "initials": "B"}, {"family": "Rutishauser", "given": "Dorothea", "initials": "D"}, {"family": "Aarsland", "given": "Dag", "initials": "D"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "journal article", "published": "2017-02-07", "journal": {"volume": "7", "issn": "2045-2322", "issue": null, "pages": "41929", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "The human blood proteome is frequently assessed by protein abundance profiling using a combination of liquid chromatography and tandem mass spectrometry (LC-MS/MS). In traditional sequence database search, many good-quality MS/MS data remain unassigned. Here we uncover the hidden part of the blood proteome via novel SpotLight approach. This method combines de novo MS/MS sequencing of enriched antibodies and co-extracted proteins with subsequent label-free quantification of new and known peptides in both enriched and unfractionated samples. In a pilot study on differentiating early stages of Alzheimer's disease (AD) from Dementia with Lewy Bodies (DLB), on peptide level the hidden proteome contributed almost as much information to patient stratification as the apparent proteome. Intriguingly, many of the new peptide sequences are attributable to antibody variable regions, and are potentially indicative of disease etiology. When the hidden and apparent proteomes are combined, the accuracy of differentiating AD (n = 97) and DLB (n = 47) increased from \u224885% to \u224895%. The low added burden of SpotLight proteome analysis makes it attractive for use in clinical settings.", "doi": "10.1038/srep41929", "pmid": "28167817", "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [{"db": "pii", "key": "srep41929"}, {"db": "pmc", "key": "PMC5294601"}], "notes": [], "created": "2020-01-23T13:29:59.536Z", "modified": "2021-07-08T08:58:46.741Z"}, {"entity": "publication", "iuid": "5631b6846c78482388ec77a7f616eb0b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5631b6846c78482388ec77a7f616eb0b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5631b6846c78482388ec77a7f616eb0b"}}, "title": "Human IgM Antibodies to Malondialdehyde Conjugated With Albumin Are Negatively Associated With Cardiovascular Disease Among 60-Year-Olds.", "authors": [{"family": "Thiagarajan", "given": "Divya", "initials": "D"}, {"family": "Frosteg\u00e5rd", "given": "Anna G", "initials": "AG"}, {"family": "Singh", "given": "Sudhir", "initials": "S"}, {"family": "Rahman", "given": "Mizanur", "initials": "M"}, {"family": "Liu", "given": "Anquan", "initials": "A"}, {"family": "Vikstr\u00f6m", "given": "Max", "initials": "M"}, {"family": "Leander", "given": "Karin", "initials": "K"}, {"family": "Gigante", "given": "Bruna", "initials": "B"}, {"family": "Hellenius", "given": "Mai-Lis", "initials": "ML"}, {"family": "Zhang", "given": "Bo", "initials": "B"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}, {"family": "de Faire", "given": "Ulf", "initials": "U"}, {"family": "Lundstr\u00f6m", "given": "Susanna L", "initials": "SL"}, {"family": "Frosteg\u00e5rd", "given": "Johan", "initials": "J"}], "type": "journal article", "published": "2016-12-20", "journal": {"title": "J Am Heart Assoc", "issn": "2047-9980", "volume": "5", "issue": "12", "issn-l": "2047-9980"}, "abstract": "Malondialdehyde (MDA) is generated during lipid peroxidation as in oxidized low-density lipoprotein, but antibodies against oxidized low-density lipoprotein show variable results in clinical studies. We therefore studied the risk of cardiovascular disease (CVD) associated with IgM antibodies against MDA conjugated with human albumin (anti-MDA).\n\nIn a 5- to 7-year follow-up of 60-year-old men and women from Stockholm County previously screened for cardiovascular risk factors (2039 men, 2193 women), 209 incident CVD cases (defined as new events of coronary heart disease, fatal and nonfatal myocardial infarction, ischemic stroke, and hospitalization for angina pectoris) and 620 age- and sex-matched controls were tested for IgM anti-MDA by ELISA. Antibody peptide/protein characterization was done using a proteomics de novo sequencing approach. After adjustment for smoking, body-mass index, type 2 diabetes mellitus, hyperlipidemia, and hypertension, an increased CVD risk was observed in the low IgM anti-MDA percentiles (below 10th and 25th) (odds ratio and 95% CI: 2.0; 1.19-3.36 and 1.67; 1.16-2.41, respectively). Anti-MDA above the 66th percentile was associated with a decreased CVD risk (odds ratio 0.68; CI: 0.48-0.98). After stratification by sex, associations were only present among men. IgM anti-MDA levels were lower among cases (median [interquartile range]: 141.0 [112.7-164.3] versus 147.4 [123.5-169.6]; P=0.0177), even more so among men (130.6 [107.7-155.3] versus 143.0 [120.1-165.2]; P=0.001). The IgM anti-MDA variable region profiles are distinctly different and also more homologous in their content (correlates strongly with fewer peptides) than control antibodies (not binding MDA).\n\nIgM anti-MDA is a protection marker for CVD. This finding could have diagnostic and therapeutic implications.", "doi": "10.1161/JAHA.116.004415", "pmid": "27998914", "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "JAHA.116.004415"}, {"db": "pmc", "key": "PMC5210446"}], "notes": [], "created": "2020-01-23T13:39:00.134Z", "modified": "2021-07-08T08:58:46.771Z"}, {"entity": "publication", "iuid": "f0189e06f40849b6aa396efe9d60aad1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f0189e06f40849b6aa396efe9d60aad1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f0189e06f40849b6aa396efe9d60aad1"}}, "title": "Validation and development of MTH1 inhibitors for treatment of cancer.", "authors": [{"family": "Warpman Berglund", "given": "U", "initials": "U"}, {"family": "Sanjiv", "given": "K", "initials": "K"}, {"family": "Gad", "given": "H", "initials": "H"}, {"family": "Kalder\u00e9n", "given": "C", "initials": "C"}, {"family": "Koolmeister", "given": "T", "initials": "T"}, {"family": "Pham", "given": "T", "initials": "T"}, {"family": "Gokturk", "given": "C", "initials": "C"}, {"family": "Jafari", "given": "R", "initials": "R"}, {"family": "Maddalo", "given": "G", "initials": "G"}, {"family": "Seashore-Ludlow", "given": "B", "initials": "B"}, {"family": "Chernobrovkin", "given": "A", "initials": "A"}, {"family": "Manoilov", "given": "A", "initials": "A"}, {"family": "Pateras", "given": "I S", "initials": "IS"}, {"family": "Rasti", "given": "A", "initials": "A"}, {"family": "Jemth", "given": "A-S", "initials": "AS"}, {"family": "Alml\u00f6f", "given": "I", "initials": "I"}, {"family": "Loseva", "given": "O", "initials": "O"}, {"family": "Visnes", "given": "T", "initials": "T"}, {"family": "Einarsdottir", "given": "B O", "initials": "BO"}, {"family": "Gaugaz", "given": "F Z", "initials": "FZ"}, {"family": "Saleh", "given": "A", "initials": "A"}, {"family": "Platzack", "given": "B", "initials": "B"}, {"family": "Wallner", "given": "O A", "initials": "OA"}, {"family": "Vallin", "given": "K S A", "initials": "KS"}, {"family": "Henriksson", "given": "M", "initials": "M"}, {"family": "Wakchaure", "given": "P", "initials": "P"}, {"family": "Borhade", "given": "S", "initials": "S"}, {"family": "Herr", "given": "P", "initials": "P"}, {"family": "Kallberg", "given": "Y", "initials": "Y"}, {"family": "Baranczewski", "given": "P", "initials": "P"}, {"family": "Homan", "given": "E J", "initials": "EJ"}, {"family": "Wiita", "given": "E", "initials": "E"}, {"family": "Nagpal", "given": "V", "initials": "V"}, {"family": "Meijer", "given": "T", "initials": "T"}, {"family": "Schipper", "given": "N", "initials": "N"}, {"family": "Rudd", "given": "S G", "initials": "SG"}, {"family": "Br\u00e4utigam", "given": "L", "initials": "L"}, {"family": "Lindqvist", "given": "A", "initials": "A"}, {"family": "Filppula", "given": "A", "initials": "A"}, {"family": "Lee", "given": "T-C", "initials": "TC"}, {"family": "Artursson", "given": "P", "initials": "P"}, {"family": "Nilsson", "given": "J A", "initials": "JA"}, {"family": "Gorgoulis", "given": "V G", "initials": "VG"}, {"family": "Lehti\u00f6", "given": "J", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Zubarev", "given": "R A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}, {"family": "Scobie", "given": "M", "initials": "M"}, {"family": "Helleday", "given": "T", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}], "type": "journal article", "published": "2016-12-00", "journal": {"volume": "27", "issn": "1569-8041", "issue": "12", "pages": "2275-2283", "title": "Ann. Oncol.", "issn-l": "0923-7534"}, "abstract": "Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment.\n\nHuman cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA or shRNA. 8-oxodG was measured by immunostaining and modified comet assay. Thermal Proteome profiling, proteomics, cellular thermal shift assays, kinase and CEREP panel were used for target engagement, mode of action and selectivity investigations of MTH1 inhibitors. Effect of MTH1 inhibition on tumour growth was explored in BRAF V600E-mutated malignant melanoma patient derived xenograft and human colon cancer SW480 and HCT116 xenograft models.\n\nHere, we demonstrate that recently described MTH1 inhibitors, which fail to kill cancer cells, also fail to introduce the toxic oxidized nucleotides into DNA. We also describe a new MTH1 inhibitor TH1579, (Karonudib), an analogue of TH588, which is a potent, selective MTH1 inhibitor with good oral availability and demonstrates excellent pharmacokinetic and anti-cancer properties in vivo.\n\nWe demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.", "doi": "10.1093/annonc/mdw429", "pmid": "27827301", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Clinical Proteomics Mass spectrometry": "Collaborative", "Chemical Proteomics": "Service", "Advanced Mass Spectrometry Proteomics": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics (NBIS)": "Collaborative", "Chemical Biology Consortium Sweden": "Collaborative", "Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0923-7534(19)36552-4"}], "notes": "Laboratories for Chemical Biology at Karolinska Institutet (LCBKI)\r\nADME of Therapeutics (UDOPP)", "created": "2017-05-03T12:58:49.192Z", "modified": "2025-10-17T13:05:09.110Z"}, {"entity": "publication", "iuid": "d7d7ca0a659742c58af9a9b5a57722a3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d7d7ca0a659742c58af9a9b5a57722a3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d7d7ca0a659742c58af9a9b5a57722a3"}}, "title": "Application of amide hydrogen/deuterium exchange mass spectrometry for epitope mapping in human cystatin C.", "authors": [{"family": "Pr\u0105dzi\u0144ska", "given": "Martyna", "initials": "M"}, {"family": "Behrendt", "given": "Izabela", "initials": "I"}, {"family": "Astorga-Wells", "given": "Juan", "initials": "J"}, {"family": "Manoilov", "given": "Aleksandr", "initials": "A"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}, {"family": "Ko\u0142odziejczyk", "given": "Aleksandra S", "initials": "AS"}, {"family": "Rodziewicz-Motowid\u0142o", "given": "Sylwia", "initials": "S"}, {"family": "Czaplewska", "given": "Paulina", "initials": "P"}], "type": "journal article", "published": "2016-12-00", "journal": {"volume": "48", "issn": "1438-2199", "issue": "12", "pages": "2809-2820", "title": "Amino Acids", "issn-l": "0939-4451"}, "abstract": "Human cystatin C (hCC) is a small cysteine protease inhibitor whose oligomerization by propagated domain swapping is linked to certain neurological disorders. One of the ways to prevent hCC dimerization and fibrillogenesis is to enable its interaction with a proper antibody. Herein, the sites of interaction of hCC with dimer-preventing mouse monoclonal anti-hCC antibodies Cyst28 are studied and compared with the binding sites found for mAb Cyst10 that has almost no effect on hCC dimerization. In addition, hCC epitopes in complexes with native polyclonal antibodies extracted from human serum were studied. The results obtained with hydrogen-deuterium exchange mass spectrometry (HDX MS) were compared with the previous findings made using the excision/extraction MS approach. The main results from the two complementary MS-based approaches are found to be in agreement with each other, with some differences being attributed to the specificity of each method. The findings of the current studies may be important for future design of hCC dimerization inhibitors.", "doi": "10.1007/s00726-016-2316-y", "pmid": "27573935", "labels": {"Chemical Proteomics": "Collaborative", "Advanced Mass Spectrometry Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1007/s00726-016-2316-y"}, {"db": "pmc", "key": "PMC5107209"}], "notes": [], "created": "2017-05-03T13:02:24.789Z", "modified": "2021-07-08T08:58:46.859Z"}, {"entity": "publication", "iuid": "5df9099d3938467aa3723647d00491f1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5df9099d3938467aa3723647d00491f1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5df9099d3938467aa3723647d00491f1"}}, "title": "Functional and Structural Characterization of a Novel HLA-DRB1*04:01-Restricted \u03b1-Enolase T Cell Epitope in Rheumatoid Arthritis.", "authors": [{"family": "Gerstner", "given": "Christina", "initials": "C"}, {"family": "Dubnovitsky", "given": "Anatoly", "initials": "A"}, {"family": "Sandin", "given": "Charlotta", "initials": "C"}, {"family": "Kozhukh", "given": "Genadiy", "initials": "G"}, {"family": "Uchtenhagen", "given": "Hannes", "initials": "H"}, {"family": "James", "given": "Eddie A", "initials": "EA"}, {"family": "R\u00f6nnelid", "given": "Johan", "initials": "J"}, {"family": "Ytterberg", "given": "Anders Jimmy", "initials": "AJ"}, {"family": "Pieper", "given": "Jennifer", "initials": "J"}, {"family": "Reed", "given": "Evan", "initials": "E"}, {"family": "Tandre", "given": "Karolina", "initials": "K"}, {"family": "Rieck", "given": "Mary", "initials": "M"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L"}, {"family": "Sandalova", "given": "Tatyana", "initials": "T"}, {"family": "Buckner", "given": "Jane H", "initials": "JH"}, {"family": "Achour", "given": "Adnane", "initials": "A"}, {"family": "Malmstr\u00f6m", "given": "Vivianne", "initials": "V"}], "type": "journal article", "published": "2016-11-14", "journal": {"title": "Front Immunol", "issn": "1664-3224", "volume": "7", "issue": null, "pages": "494", "issn-l": "1664-3224"}, "abstract": "Antibodies to citrullinated proteins, common in rheumatoid arthritis (RA) patients, are strongly associated to a specific set of HLA-DR alleles including HLA-DRB1*04:01, *04:04, and *01:01. Here, we first demonstrate that autoantibody levels toward the dominant citrullinated B cell epitope from \u03b1-enolase are significantly elevated in HLA-DRB1*04:01-positive RA patients. Furthermore, we identified \u03b1-enolase-derived T cell epitopes and demonstrated that native and citrullinated versions of several peptides bind with different affinities to HLA-DRB1*04:01, *04:04, and *01:01. The citrulline residues in the eight identified peptides are distributed throughout the entire length of the presented epitopes and more specifically, localized at peptide positions p-2, p2, p4, p6, p7, p10, and p11. Importantly, in contrast to its native version peptide 26 (TSKGLF RAAVPSGAS), the HLA-DRB1*04:01-restricted citrullinated peptide Cit26 (TSKGLFCitAAVPSGAS) elicited significant functional T cell responses in primary cells from RA patients. Comparative analysis of the crystal structures of HLA-DRB1*04:01 in complex with peptide 26 or Cit26 demonstrated that the posttranslational modification did not alter the conformation of the peptide. And since citrullination is the only structural difference between the two complexes, this indicates that the neo-antigen Cit26 is recognized by T cells with high specificity to the citrulline residue.", "doi": "10.3389/fimmu.2016.00494", "pmid": "27895642", "labels": {"Chemical Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC5108039"}], "notes": [], "created": "2020-01-23T13:42:07.432Z", "modified": "2021-07-08T08:58:46.776Z"}, {"entity": "publication", "iuid": "14e13ca9beaa4fd0ac6f14a2ab118b32", "links": {"self": {"href": "https://publications.scilifelab.se/publication/14e13ca9beaa4fd0ac6f14a2ab118b32.json"}, "display": {"href": "https://publications.scilifelab.se/publication/14e13ca9beaa4fd0ac6f14a2ab118b32"}}, "title": "Isolation and characterization of autoantibodies against human cystatin C.", "authors": [{"family": "Pr\u0105dzi\u0144ska", "given": "Martyna", "initials": "M"}, {"family": "Behrendt", "given": "Izabela", "initials": "I"}, {"family": "Spodzieja", "given": "Marta", "initials": "M"}, {"family": "Ko\u0142odziejczyk", "given": "Aleksandra S", "initials": "AS"}, {"family": "Rodziewicz-Motowid\u0142o", "given": "Sylwia", "initials": "S"}, {"family": "Szyma\u0144ska", "given": "Aneta", "initials": "A"}, {"family": "Lundstr\u00f6m", "given": "Susanna L", "initials": "SL"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}, {"family": "Macur", "given": "Katarzyna", "initials": "K"}, {"family": "Czaplewska", "given": "Paulina", "initials": "P"}], "type": "journal article", "published": "2016-11-00", "journal": {"volume": "48", "issn": "1438-2199", "issue": "11", "pages": "2501-2518", "title": "Amino Acids", "issn-l": "0939-4451"}, "abstract": "Hereditary cystatin C amyloid angiopathy (HCCAA) is a severe neurodegenerative disorder related to the point mutation in cystatin C gene resulting in human cystatin C (hCC) L68Q variant. One of the potential immunotherapeutic approaches to HCCAA treatment is based on naturally occurring antibodies against cystatin C. A recent growing interest in autoantibodies, especially in the context of neurodegenerative diseases, emerges from their potential use as valuable diagnostic markers and for controlling protein aggregation. In this work, we present characteristics of natural anti-hCC antibodies isolated from the IgG fraction of human serum by affinity chromatography. The electrophoresis (1-D and 2-D) results demonstrated that the isolated NAbs are a polyclonal mixture, but their electrophoretic properties did not allow to classify the new autoantibodies to any particular type of IgG. The Fc-glycan status of the studied autoantibodies was assessed using mass spectrometry analysis. For the isolated NAbs, the epitopic fragments in hCC sequence were identified by MS-assisted proteolytic excision of the immune complex and compared with the ones predicted theoretically. The knowledge of hCC fragments binding to NAbs and other ligands may contribute to the search for new diagnostic methods for amyloidosis of different types and the search for their treatment.", "doi": "10.1007/s00726-016-2271-7", "pmid": "27277188", "labels": {"Chemical Proteomics": "Collaborative", "Advanced Mass Spectrometry Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1007/s00726-016-2271-7"}], "notes": [], "created": "2017-05-03T13:02:24.496Z", "modified": "2021-07-08T08:58:46.735Z"}, {"entity": "publication", "iuid": "7e978eacffdd4fc087e580e78b2686ae", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7e978eacffdd4fc087e580e78b2686ae.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7e978eacffdd4fc087e580e78b2686ae"}}, "title": "Establishing a Proteomics-Based Monocyte Assay To Assess Differential Innate Immune Activation Responses.", "authors": [{"family": "Tarasova", "given": "Nataliya K", "initials": "NK"}, {"family": "Ytterberg", "given": "A Jimmy", "initials": "AJ"}, {"family": "Lundberg", "given": "Karin", "initials": "K"}, {"family": "Zhang", "given": "Xing-Mei", "initials": "X"}, {"family": "Harris", "given": "Robert A", "initials": "RA"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "journal article", "published": "2016-07-01", "journal": {"volume": "15", "issn": "1535-3907", "issue": "7", "pages": "2337-2345", "title": "J. Proteome Res.", "issn-l": "1535-3893"}, "abstract": "Innate immune cells are complex systems that can be simultaneously activated in a variety of ways. Common methods currently used to estimate the response of innate immune cells to stimuli are usually biased toward a single mode of activation. The aim of this study was to assess the possibility of designing an assay based on unbiased proteome analysis that would be capable of predicting the complex response of the innate immune system to various challenges. Monocytes were used as representative cells of the innate immune system. The underlying hypothesis was that their proteome response to different activating molecules would reflect the immunogenicity of these molecules. To identify the main modes of response, we treated the human monocytic THP-1 cell line with nine different stimuli. Differentiation and activation were determined to be the two major modes of monocyte response, with PMA causing the strongest differentiation and Pam3CSK4 causing the strongest proinflammatory activation. The established assay was applied to characterize the monocyte response to epidermal growth factor peptide containing isoaspartate, which induced differentiation but not proinflammatory activation. Because of its versatility, robustness, and specificity, this new assay is likely to find a niche among the more established immunological methods.", "doi": "10.1021/acs.jproteome.6b00422", "pmid": "27223872", "labels": {"Chemical Proteomics": "Technology development", "Advanced Mass Spectrometry Proteomics": "Collaborative"}, "xrefs": [], "notes": [], "created": "2017-05-03T13:02:25.092Z", "modified": "2021-07-08T08:58:46.794Z"}, {"entity": "publication", "iuid": "12b3956ca0364a68ab3b928d392072ae", "links": {"self": {"href": "https://publications.scilifelab.se/publication/12b3956ca0364a68ab3b928d392072ae.json"}, "display": {"href": "https://publications.scilifelab.se/publication/12b3956ca0364a68ab3b928d392072ae"}}, "title": "DeMix-Q: Quantification-Centered Data Processing Workflow.", "authors": [{"family": "Zhang", "given": "Bo", "initials": "B"}, {"family": "K\u00e4ll", "given": "Lukas", "initials": "L"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "comparative study", "published": "2016-04-00", "journal": {"title": "Mol. Cell Proteomics", "issn": "1535-9484", "volume": "15", "issue": "4", "pages": "1467-1478", "issn-l": "1535-9476"}, "abstract": "For historical reasons, most proteomics workflows focus on MS/MS identification but consider quantification as the end point of a comparative study. The stochastic data-dependent MS/MS acquisition (DDA) gives low reproducibility of peptide identifications from one run to another, which inevitably results in problems with missing values when quantifying the same peptide across a series of label-free experiments. However, the signal from the molecular ion is almost always present among the MS(1)spectra. Contrary to what is frequently claimed, missing values do not have to be an intrinsic problem of DDA approaches that perform quantification at the MS(1)level. The challenge is to perform sound peptide identity propagation across multiple high-resolution LC-MS/MS experiments, from runs with MS/MS-based identifications to runs where such information is absent. Here, we present a new analytical workflow DeMix-Q (https://github.com/userbz/DeMix-Q), which performs such propagation that recovers missing values reliably by using a novel scoring scheme for quality control. Compared with traditional workflows for DDA as well as previous DIA studies, DeMix-Q achieves deeper proteome coverage, fewer missing values, and lower quantification variance on a benchmark dataset. This quantification-centered workflow also enables flexible and robust proteome characterization based on covariation of peptide abundances.", "doi": "10.1074/mcp.O115.055475", "pmid": "26729709", "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [{"db": "pii", "key": "O115.055475"}, {"db": "pmc", "key": "PMC4824868"}], "notes": [], "created": "2020-01-23T13:47:23.663Z", "modified": "2021-07-08T08:58:46.729Z"}, {"entity": "publication", "iuid": "2c162d656e014b59ab15b97ca25bd449", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2c162d656e014b59ab15b97ca25bd449.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2c162d656e014b59ab15b97ca25bd449"}}, "title": "Functional Identification of Target by Expression Proteomics (FITExP) reveals protein targets and highlights mechanisms of action of small molecule drugs.", "authors": [{"family": "Chernobrovkin", "given": "Alexey", "initials": "A"}, {"family": "Marin-Vicente", "given": "Consuelo", "initials": "C"}, {"family": "Visa", "given": "Neus", "initials": "N"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "journal article", "published": "2015-06-08", "journal": {"volume": "5", "issn": "2045-2322", "issue": null, "pages": "11176", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "Phenomenological screening of small molecule libraries for anticancer activity yields potentially interesting candidate molecules, with a bottleneck in the determination of drug targets and the mechanism of anticancer action. We have found that, for the protein target of a small-molecule drug, the abundance change in late apoptosis is exceptional compared to the expectations based on the abundances of co-regulated proteins. Based on this finding, a novel method to drug target deconvolution is proposed. In a proof of principle experiment, the method yielded known targets of several common anticancer agents among a few (often, just one) likely candidates identified in an unbiased way from cellular proteome comprising more than 4,000 proteins. A validation experiment with a different set of cells and drugs confirmed the findings. As an additional benefit, mapping most specifically regulated proteins on known protein networks highlighted the mechanism of drug action. The new method, if proven to be general, can significantly shorten drug target identification, and thus facilitate the emergence of novel anticancer treatments.", "doi": "10.1038/srep11176", "pmid": "26052917", "labels": {"Chemical Proteomics": "Technology development", "Advanced Mass Spectrometry Proteomics": null}, "xrefs": [{"db": "pii", "key": "srep11176"}, {"db": "pmc", "key": "PMC4459150"}], "notes": [], "created": "2017-05-02T12:56:29.879Z", "modified": "2021-07-08T08:58:46.753Z"}]}