{"entity": "researcher", "timestamp": "2026-05-19T00:13:34.285Z", "family": "Billing", "given": "Ola", "initials": "O", "orcid": "0000-0001-5824-6263", "affiliations": ["Department of Surgical and Perioperative Sciences, Surgery, Ume\u00e5 University, SE-90187, Ume\u00e5, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/0c9507722d964ce9a32a6cd3c6d80b2c.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/0c9507722d964ce9a32a6cd3c6d80b2c"}}, "publications": [{"entity": "publication", "iuid": "c2b8ca52597945baa28d465e688f6a03", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c2b8ca52597945baa28d465e688f6a03.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c2b8ca52597945baa28d465e688f6a03"}}, "title": "A Drug Discovery Pipeline for MAPK/ERK Pathway Inhibitors in Caenorhabditis elegans.", "authors": [{"family": "Gorgo\u0144", "given": "Szymon", "initials": "S", "orcid": "0000-0002-4340-7316", "researcher": {"href": "https://publications.scilifelab.se/researcher/a450e4d8c0b54457b462679b2e217d96.json"}}, {"family": "Billing", "given": "Ola", "initials": "O", "orcid": "0000-0001-5824-6263", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c9507722d964ce9a32a6cd3c6d80b2c.json"}}, {"family": "Eriksson", "given": "Anna U", "initials": "AU", "orcid": "0000-0002-8853-1863", "researcher": {"href": "https://publications.scilifelab.se/researcher/53cfc6bb334e455d9f64172ff43e3428.json"}}, {"family": "Hemmingsson", "given": "Oskar", "initials": "O", "orcid": "0000-0003-1732-168X", "researcher": {"href": "https://publications.scilifelab.se/researcher/33b77136c4d54877aa093c2b64f64489.json"}}], "type": "journal article", "published": "2024-09-01", "journal": {"title": "Cancer Res Commun", "issn": "2767-9764", "issn-l": null, "volume": "4", "issue": "9", "pages": "2454-2462"}, "abstract": "Oncogenic signaling through the MAPK/ERK pathway drives tumor progression in many cancers. Although targeted MAPK/ERK pathway inhibitors improve survival in selected patients, most tumors are resistant. New drugs could be identified in small-animal models that, unlike in vitro models, can address oral uptake, compound bioavailability, and toxicity. This requires pharmacologic conformity between human and model MAPK/ERK pathways and available phenotypic assays. In this study, we test if the conserved MAPK/ERK pathway in Caenorhabditis elegans could serve as a model for pharmacological inhibition and develop in vivo pipelines for high-throughput compound screens. Using fluorescence-based image analysis of vulva development as a readout for MAPK/ERK activity, we obtained excellent assay Z-scores for the MEK inhibitors trametinib (Z = 0.95), mirdametinib (Z = 0.93), and AZD8330 (Z = 0.87), as well as the ERK inhibitor temuterkib (Z = 0.86). The throughput was 800 wells per hour, with an average seed density of 25.5 animals per well. Readouts included drug efficacy, toxicity, and pathway specificity, which was tested against pathway activating upstream (lin-15)- and downstream (lin-1) mutants. To validate the model in a high-throughput setting, we screened a blinded library of 433 anticancer compounds and identified four MEK inhibitors among seven positive hits. Our results highlight a high degree of pharmacological conformity between C. elegans and human MAPK/ERK pathways, and the presented high-throughput pipeline may discover and characterize novel inhibitors in vivo.\r\n\r\nMany tumors depend on MAPK/ERK signaling to sustain growth, avoid cell death, and metastasize. We show that specific and clinically relevant MAPK/ERK signaling inhibitors can be discovered in vivo with a high-throughput screening pipeline in small animals.", "doi": "10.1158/2767-9764.CRC-24-0221", "pmid": "39212544", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11409438"}, {"db": "pii", "key": "747452"}], "notes": [], "created": "2024-12-02T15:30:18.753Z", "modified": "2025-10-17T13:04:27.281Z"}, {"entity": "publication", "iuid": "2c302588fb0a42b3be111c75c663961d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2c302588fb0a42b3be111c75c663961d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2c302588fb0a42b3be111c75c663961d"}}, "title": "LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes.", "authors": [{"family": "Herdenberg", "given": "Carl", "initials": "C"}, {"family": "Mutie", "given": "Pascal M", "initials": "PM"}, {"family": "Billing", "given": "Ola", "initials": "O", "orcid": "0000-0001-5824-6263", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c9507722d964ce9a32a6cd3c6d80b2c.json"}}, {"family": "Abdullah", "given": "Ahmad", "initials": "A", "orcid": "0000-0003-3502-5948", "researcher": {"href": "https://publications.scilifelab.se/researcher/dca27d1581fc4760b2b8a34f6f53e6f6.json"}}, {"family": "Strawbridge", "given": "Rona J", "initials": "RJ", "orcid": "0000-0001-8506-3585", "researcher": {"href": "https://publications.scilifelab.se/researcher/8ac5060a3b37466dae002d4ad8f4d0ac.json"}}, {"family": "Dahlman", "given": "Ingrid", "initials": "I"}, {"family": "Tuck", "given": "Simon", "initials": "S"}, {"family": "Holmlund", "given": "Camilla", "initials": "C"}, {"family": "Arner", "given": "Peter", "initials": "P", "orcid": "0000-0002-6208-6220", "researcher": {"href": "https://publications.scilifelab.se/researcher/95b10e9b283e4806a8d97755a43e4cec.json"}}, {"family": "Henriksson", "given": "Roger", "initials": "R"}, {"family": "Franks", "given": "Paul W", "initials": "PW", "orcid": "0000-0002-0520-7604", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ebbf40c0f7e49dd8c75a2b6cbf27276.json"}}, {"family": "Hedman", "given": "H\u00e5kan", "initials": "H", "orcid": "0000-0001-6891-6996", "researcher": {"href": "https://publications.scilifelab.se/researcher/6b1b2d57a55e415aa17acbd0318a019e.json"}}], "type": "journal article", "published": "2021-01-19", "journal": {"title": "Commun Biol", "issn": "2399-3642", "volume": "4", "issue": "1", "pages": "90", "issn-l": "2399-3642"}, "abstract": "Leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins have been implicated as regulators of growth factor signaling; however, the possible redundancy among mammalian LRIG1, LRIG2, and LRIG3 has hindered detailed elucidation of their physiological functions. Here, we show that Lrig-null mouse embryonic fibroblasts (MEFs) are deficient in adipogenesis and bone morphogenetic protein (BMP) signaling. In contrast, transforming growth factor-beta (TGF-\u03b2) and receptor tyrosine kinase (RTK) signaling appeared unaltered in Lrig-null cells. The BMP signaling defect was rescued by ectopic expression of LRIG1 or LRIG3 but not by expression of LRIG2. Caenorhabditis elegans with mutant LRIG/sma-10 variants also exhibited a lipid storage defect. Human LRIG1 variants were strongly associated with increased body mass index (BMI) yet protected against type 2 diabetes; these effects were likely mediated by altered adipocyte morphology. These results demonstrate that LRIG proteins function as evolutionarily conserved regulators of lipid metabolism and BMP signaling and have implications for human disease.", "doi": "10.1038/s42003-020-01613-w", "pmid": "33469151", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s42003-020-01613-w"}, {"db": "pmc", "key": "PMC7815736"}], "notes": [], "created": "2021-12-09T20:01:11.461Z", "modified": "2025-10-17T13:03:16.382Z"}]}