We are mainly interested in the interactions of residential brain macrophages (microglia) and brain tumours. Microglia have the outstanding capability to sense injuries and infections in the brain immediately, to migrate to the site of lesion and to phagocytose detrimental material. Strikingly a comparable course of events is observed during tumour progression where microglia are attracted to the tumour and colonize the tumour. But instead of the expected anti-tumoural activity they achieve pro-tumoural functions and promote tumour growth. However due to the difficulty to monitor the early events of tumour colonization by microglia in vivo we are just beginning to understand these complex mechanisms.
The optically transparent zebrafish larvae allow us studying the interactions of microglia and brain tumours for the first time in vivo. In particular the opportunity to image cellular interactions at high temporal and spatial resolution in vivo combined with the possibility to interfere genetically and pharmacologically make the zebrafish an ideal model for our research.
Using this new brain tumour model we are approaching the following questions:
• Which mechanisms are required to attract microglia to the tumour?
• What are the signals that lead to the pro-tumoural activity of microglia?
• Is it possible to circumvent the switch to pro-tumoural activity or even to induce anti-tumoural activity?
For further information, please see also: http://www.cnr.ed.ac.uk/Research/sieger.html
Chuang H., van Rossum D., Sieger D., Pukrop T. et al. (2013) Carcinoma cells misuse the host tissue damage response to invade the brain. Glia., 61 (8) : 1331-46.
Sieger D., Peri, F. (2013) Animal models for studying microglia: The first, the popular, and the new. Glia., 61 (1) : 3–9.
Sieger D., Moritz C., Ziegenhals T., Prykhozhij S., Peri F. (2012) Long-range Ca2+ waves transmit brain damage signals to microglia. Dev. Cell., 22 (6) : 1138-48.
Böcke A., Sieger D., Kashkar H., Krönke M. (2012) FAN mediates navigational capacity of macro¬phages responding to wounds and infection-live imaging studies in zebrafish larvae. J. Immunol., 189 (4) : 1559-66.
Sieger D., Stein C., Neifer D., van der Sar AM., Leptin M. (2009) The role of gamma interferon in innate immunity in the zebrafish embryo. Dis. Model Mech., 2 (11-12) : 571-81.
2012 Chancellor’s Fellowship, University of Edinburgh, UK
2009 EMBO Long-Term Fellowship