Invasive Migration of Immune Cells

Daria Siekhaus

The formation of the body, the functioning of the immune system and the spread of cancer all depend on the ability of cells to migrate. We strive to understand this crucial process and in particular the question of how cells move within the complicated environment of an organism and penetrate through barriers that lie in their way. We address these questions in the fruit fly Drosophila melanogaster by studying the developmental migration of immune cells which all move from the location of their birth to disparate regions of the embryo through precise paths. One of these trajectories requires the cells to invade a tissue barrier, in a process that we have shown utilizes molecular components also required in mammalian immune cells and metastatic cancer cells to penetrate the endothelial vasculature. We have identified many genes required for this invasive movement. Using a powerful combination of imaging, genetics, cell biology and biophysics we seek to understand the functions of these genes, the pathways they act in, and the strategies and principles that underlie invasive migration. We hope to translate what we learn from our Drosophila studies to autoimmunity and metastasis.


Daria Siekhaus
Institute of Science and Technology Austria (IST Austria)
Am Campus 1
A – 3400 Klosterneuburg
Phone: +43 (0)2243 9000-5001

CV and publication list

Alexandra Mally

Phone: +43 (0)2243 9000-1105


  • Maria Akhmanova, Postdoc
  • Julia Biebl, Laboratory Technician
  • Shamsi Emtenani, PhD Student
  • Attila György, Laboratory Technician
  • Michaela Misova, PhD Student (jointly with Sixt group)
  • Justine Renno, Laboratory Technician
  • Marko Roblek, Postdoc
  • Katarina Valoskova, PhD Student
  • Stephanie Wachner, PhD Student

Current Projects

Altered properties of invaded tissues: We are conducting mechanobiological, cell biological, and genetic experiments to understand what changes are triggered in the invaded tissues to permit macrophage entry and by which mechanism they are induced.  

The transcriptional program of invasion: We have identified a set of transcription factors required specifically for invasion and are investigating their interplay, upstream regulation, and downstream targets.

Novel players required for invasion: We are characterizing the role of proteins required for Drosophila invasive migration which are conserved with vertebrates but previously uninvestigated in any system.  These include a transporter in the Golgi and a protein localized to the nucleus. These experiments utilise both Drosophila embryos and vertebrate immune and cancer cells.

Selected Publications

  • Valoskova, K., Biebl, J., Roblek, M., Emtenani , S., Gyoergy, A., Misova, M., Ratheesh, A., Shkarina, K., Larsen, I.S.B, Vakhrushev, S.Y., Clausen, H., Siekhaus, D.E. (2019) A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. eLife 2019;8:e41801
  • Ratheesh, A, Biebl, J., Vesela, J., Smutny, M., Papusheva, E. Krens, S.F.G, Kaufmann, W., Gyoergy, A., Casano, A.M., Siekhaus D.E. (2018) Drosophila TNF modulates tissue tension in the embryo to facilitate macrophage invasive migration. Developmental Cell 7;45(3):331-346
  • Gyoergy, A., Roblek, M., Ratheesh, A., Valoskova, K., Belyaeva, V., Wachner, S., Matsubayashi, Y., Sanchez-Sanchez, B.J., Stramer, B., and Siekhaus D.E. (2018) Tools allowing independent visualization and genetic manipulation of Drosophila melanogaster macrophages and surrounding tissues. G3 (Bethesda) 8(3):845-857
  • Matsubayashi, Y., Louani, A., Dragu, A., Sánchez-Sánchez, B.J., Serna-Morales, E., Yolland, L., Gyoergy, A., L Vizcay, G., Fleck, R.A., Heddleston, J.M., Chew, T.L., Siekhaus D.E., Stramer B. (2017) A moving source of matrix components is essential for de novo basement membrane formation. Current Biology 27(22):3526-34
  • Ratheesh A, Belyaeva V, Siekhaus D.E. Drosophila immune cell migration and adhesion during embryonic development and larval immune responses. (2015) Current Opinion in Cell Biology 36:71-79
  • Siekhaus, D.E., Haesemeyer, M., Moffitt, O. and Lehmann, R. (2010). RhoL controls invasion and Rap1 localization during immune cell transmigration in Drosophila. Nature Cell Biology 12(6):605-610


2012-present Assistant Professor, IST Austria
2003-2011 Research Scientist, New York University Medical Center, Skirball Institute, Dept. of Developmental Genetics
1999-2003 Post-doctoral Fellow, University of California Berkeley, Dept. of Molecular Cell Biology
1998 PhD, Stanford University, Dept. of Biochemistry

Selected Distinctions

2012 Marie Curie Career Integration Grant
2009 Lennart Philipson prize, NYU Skirball Center
2000-2003 NRSA Fellowship