{"entity": "researcher", "timestamp": "2026-09-13T18:36:56.500Z", "family": "Wang", "given": "Alexander L E", "initials": "ALE", "orcid": "0000-0003-2829-7398", "affiliations": ["Department of Systems Biology, Columbia University, New York, NY, USA."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/fb0c226cb938497baf6bfe14b0ae73bf.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/fb0c226cb938497baf6bfe14b0ae73bf"}}, "publications": [{"entity": "publication", "iuid": "6a5577713cc749939f0b4b3d2c06d511", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6a5577713cc749939f0b4b3d2c06d511.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6a5577713cc749939f0b4b3d2c06d511"}}, "title": "Developmental and MAPK-responsive transcription factors regulate distinct malignant cell states and associated genetic dependencies in pancreatic cancer.", "authors": [{"family": "Laise", "given": "Pasquale", "initials": "P", "orcid": "0000-0003-1469-4704", "researcher": {"href": "https://publications.scilifelab.se/researcher/0592a382bfcf4f2d83e5d79f89bb425a.json"}}, {"family": "Turunen", "given": "Mikko", "initials": "M"}, {"family": "Curiel-Garcia", "given": "Alvaro", "initials": "A", "orcid": "0000-0001-6249-3267", "researcher": {"href": "https://publications.scilifelab.se/researcher/79ceb079786a4cf38b8899a34a008861.json"}}, {"family": "Tomassoni", "given": "Lorenzo", "initials": "L"}, {"family": "Maurer", "given": "H Carlo", "initials": "HC"}, {"family": "Elyada", "given": "Ela", "initials": "E"}, {"family": "Schmierer", "given": "Bernhard", "initials": "B", "orcid": "0000-0002-9082-7022", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3ee96f9eb454850be6db3318b28479f.json"}}, {"family": "Worley", "given": "Jeremy", "initials": "J"}, {"family": "Kesner", "given": "Jordan", "initials": "J", "orcid": "0000-0003-1330-1980", "researcher": {"href": "https://publications.scilifelab.se/researcher/50799cbc402c46519a41089455bfdd36.json"}}, {"family": "Tan", "given": "Xiangtian", "initials": "X"}, {"family": "Fernandez", "given": "Ester Calvo", "initials": "EC"}, {"family": "Xue", "given": "Yuanqing", "initials": "Y"}, {"family": "Chen", "given": "Yining", "initials": "Y"}, {"family": "Wong", "given": "Kelly", "initials": "K"}, {"family": "Wasko", "given": "Urszula N", "initials": "UN"}, {"family": "Tagore", "given": "Somnath", "initials": "S", "orcid": "0000-0001-9603-1263", "researcher": {"href": "https://publications.scilifelab.se/researcher/260f1c898af9446ab6e211daf0443638.json"}}, {"family": "Wang", "given": "Alexander L E", "initials": "ALE", "orcid": "0000-0003-2829-7398", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb0c226cb938497baf6bfe14b0ae73bf.json"}}, {"family": "Ge", "given": "Sabrina", "initials": "S", "orcid": "0000-0002-0242-753X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e4cd093c69341e393ec19a51935b0c7.json"}}, {"family": "Iuga", "given": "Alina C", "initials": "AC"}, {"family": "Griffin", "given": "Aaron T", "initials": "AT", "orcid": "0000-0002-8027-0822", "researcher": {"href": "https://publications.scilifelab.se/researcher/18d3aa98af1f4c898bf892a33d86dfb3.json"}}, {"family": "Wong", "given": "Winston", "initials": "W"}, {"family": "Manji", "given": "Gulam A", "initials": "GA", "orcid": "0009-0000-7459-6036", "researcher": {"href": "https://publications.scilifelab.se/researcher/a1495b2f669e49b9a1747eb45a025c7e.json"}}, {"family": "Alvarez", "given": "Mariano J", "initials": "MJ"}, {"family": "Notta", "given": "Faiyaz", "initials": "F"}, {"family": "Tuveson", "given": "David A", "initials": "DA", "orcid": "0000-0002-8017-2712", "researcher": {"href": "https://publications.scilifelab.se/researcher/f5d2a48d48ea4ddfb0bb1c64ed4ad592.json"}}, {"family": "Olive", "given": "Kenneth P", "initials": "KP", "orcid": "0000-0002-3392-8994", "researcher": {"href": "https://publications.scilifelab.se/researcher/23f056db63144804b1df283e9f5335d3.json"}}, {"family": "Califano", "given": "Andrea", "initials": "A", "orcid": "0000-0003-4742-3679", "researcher": {"href": "https://publications.scilifelab.se/researcher/4aeec80fda63405eaab09827e3f9b704.json"}}], "type": "journal article", "published": "2026-09-00", "journal": {"title": "Nat. Genet.", "issn": "1546-1718", "issn-l": "1061-4036", "volume": "58", "issue": "9", "pages": "2226-2239"}, "abstract": "There is broad consensus that the malignant epithelial cells of human pancreatic ductal adenocarcinoma (PDA) comprise multiple, molecularly distinct states. Yet precise characterization of how these are regulated-including their mechanistic determinants, dependencies, plasticity and functional properties-remains elusive. Single-cell master regulator (MR) analysis of multiple PDA cohorts identified malignant cells in three co-existing, molecularly distinct developmental lineage states, with distinct histopathological morphologies and spatial architecture. These include a poorly differentiated lineage driven by epithelial-mesenchymal-transition-related MRs and two well-differentiated states driven by gastrointestinal epithelial development and pancreatic development MRs, respectively. Furthermore, each state comprises two epigenetically distinct substates with low versus high MAPK signaling activity. Barcode-based lineage tracing confirmed both spontaneous and treatment-dependent cross-state plasticity. Furthermore, loss-of-function studies confirmed state-specific MR essentiality, while their ectopic expression effectively reprogrammed cell state, in vitro and in vivo, thus providing a mechanism-based foundation for PDA heterogeneity and a roadmap for pharmacological targeting.", "doi": "10.1038/s41588-026-02714-8", "pmid": "42649389", "labels": {"CRISPR Functional Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC13553295"}, {"db": "pii", "key": "10.1038/s41588-026-02714-8"}], "notes": [], "created": "2026-09-13T11:25:50.682Z", "modified": "2026-09-13T11:27:04.942Z"}]}