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Dr. Juliane Winkler
MedUni Wien RESEARCHER OF THE MONTH September 2025
The “Researcher of the Month” jury is pleased to present this month’s award to Dr. Winkler in recognition of her recent publication in the top-tier journal Journal of Clinical Investigation titled “Single-cell analysis of breast cancer metastasis reveals epithelial-mesenchymal plasticity signatures associated with poor outcomes” [1] The importance of this study was further underscored by a commentary [2] published in the same issue of the journal.
The aim of my study was to identify why some tumors metastasize while others don’t and what is different about metastatic cells as compared to the tumor cells of the primary tumor. To study this, I profiled individual tumors cells and their matched lung metastasis using single-cell RNA-seq to get a very detailed understanding of their transcriptional phenotype. In depth computational analysis of this rich data set revealed three major findings: 1) I identified pathways in the primary tumor that can explain why some tumors can metastasize, 2) primary tumors and metastatic cells are using are very different pathways indicating a strong phenotypic adaptation of metastatic cells to their new environment and 3) tumors show a high degree of heterogeneity meaning that different tumors cells within the same tumor harboring different phenotypes and likely fulfilling different functions in regard to the metastatic capability of the tumor as a whole. We are currently working on follow-up projects to better understand how this observed intra-tumor heterogeneity impacts metastatic development.
Selected Literature
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Winkler J#, Tan W, Diadhiou CMM, McGinnis CS, Abbasi A, Hasnain S, Durney S, Atamaniuc E, Superville D, Awni L, Lee JV, Hinrichs JH, Wagner PS, Singh N, Hein MY, Borja M, Detweiler A, Liu SY, Nanjaraj A, Sitarama V, Rugo HS, Neff N, Gartner ZJ, Pisco AO#, Goga A#, Darmanis S#, Werb Z (2024). Single-cell analysis of breast cancer metastasis reveals epithelial-mesenchymal plasticity signatures associated with poor outcomes. Journal of Clinical Investigation 134, e164227. doi: 10.1172/JCI164227
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Reeves, M.Q., 2024. Mapping the transcriptional evolution of human metastatic breast cancer. J. Clin. Invest. 134, e183971. doi: 10.1172/JCI183971
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McGinnis, CS*, Patterson, DM*, Winkler, J, Conrad, DN, Hein, MY, Srivastava, V, Hu, JL, Murrow, LM, Weissman, JS, Werb, Z, Gartner, Z (2019). MULTI-seq: sample multiplexing for single-cell RNA sequencing using lipid-tagged indices. Nature Methods 16, 619–626. doi: 10.1038/s41592-019-0433-8