Life Sciences
Invasive Migration
The ability of cells to migrate is crucial for their function in the immune system, the formation of the body, and the spread of cancer. The Siekhaus group investigates how cells move within the complex environment of an organism, using the genetic power of the fruit fly to interrogate this process and identify ways in which it is regulated.
Vertebrate immune and cancer cells need to squeeze between closely connected cells to disseminate in the body. Daria Siekhaus and her group study how cells penetrate such tissue barriers, using the developmental movement of macrophages in the fruit fly Drosophila melanogaster as a model. The Siekhaus group uses a combination of imaging, genetics, cell biology, biophysics and modeling to identify the strategies that underlie tissue invasion. The group has found that a cytokine conserved in vertebrates facilitates tissue entry by reducing tension in surrounding tissues. The group has defined a novel program acting in disseminating and invading macrophages that alters glycosylation to aid invasion; this program displays molecular conservation in metastatic cancer cells. They have also defined a conserved pioneer invader program acting in macrophages that activates transcription and translation of an mRNA subset to increase tissue entry.
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Team
Current Projects
The role of cell division in regulating invasive migration | A novel transporter and its effect on glycosylation, immune function and metastasis | A conserved pioneer cell program that governs invasion through changes affecting metabolism
Publications
Akhmanova M, Emtenani S, Krueger D, György A, Pereira Guarda M, Vlasov M, Vlasov F, Akopian A, Ratheesh A, De Renzis S, Siekhaus DE. 2022. Cell division in tissues enables macrophage infiltration. Science. 376(6591), 394–396. View
Emtenani S, Martin ET, György A, Bicher J, Genger J-W, Köcher T, Akhmanova M, Pereira Guarda M, Roblek M, Bergthaler A, Hurd TR, Rangan P, Siekhaus DE. 2022. Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila. The Embo Journal. 41, e109049. View
Roblek M, Bicher J, van Gogh M, György A, Seeböck R, Szulc B, Damme M, Olczak M, Borsig L, Siekhaus DE. 2022. The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis. Frontiers in Oncology. 12, 777634. View
Belyaeva V, Wachner S, György A, Emtenani S, Gridchyn I, Akhmanova M, Linder M, Roblek M, Sibilia M, Siekhaus DE. 2022. Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila. PLoS Biology. 20(1), e3001494. View
Valosková K, Bicher J, Roblek M, Emtenani S, György A, Misova M, Ratheesh A, Rodrigues P, Shkarina K, Larsen ISB, Vakhrushev SY, Clausen H, Siekhaus DE. 2019. A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. eLife. 8, e41801. View
ReX-Link: Daria Siekhaus
Career
since 2012 Assistant Professor, Institute of Science and Technology Austria (ISTA)
2003 – 2011 Research Scientist, Skirball Institute, New York University Medical Center, USA
1999 – 2003 Postdoctoral Fellow, University of California, Berkeley, USA
1998 PhD, Stanford University, USA
Selected Distinctions
2019 Chosen for “Excellence in Peer Review” by Developmental Cell editors
2018, 2019 F1000 Prime, 2022 Faculty Opinions highlighted papers
2016 FWF Grant
2012 Marie Curie Career Integration Grant
2003 – 2005 NIH Fellowship