Dr Dirk Sieger
Our research focuses on the role of macrophages and microglia in brain tumour growth.
- 2012 – Principal Investigator, CNR
- 2009 – 2012 Postdoc, EMBL Heidelberg (Dr. Francesca Peri)
- 2006 – 2009 Postdoc, University of Cologne (Prof. Maria Leptin)
- 2002 – 2006 PhD in Genetics, University of Cologne (Prof. Diethard Tautz)
The lab is 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 to study 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?
- Katy Astell, Research Assistant/Lab Manager
- Lorna Donnelly, MSc student
- Lloyd Hamilton, PhD Student
- Julie Mazzolini, Postdoctoral Researcher
- Gregoire Morisse, Research Technician
- Brian Premkumar, MSc student
- Cancer Research UK
- Wellcome Trust-University of Edinburgh Institutional Support Fund award (ISSF)
- Dr Steven Pollard, MRC Centre for Regenerative Medicine, Edinburgh, UK
- Dr Marina Mione, KIT Karlsruhe, Germany
- Dr Asier Unciti-Broceta, Edinburgh Cancer Centre
- Dr Francesca Peri, EMBL Heidelberg, Germany
- Dr Yi Feng, MRC Centre for Inflammation Research, Edinburgh, UK
- Dr Catherina Becker, University of Edinburgh, UK
- Prof David Lyons, University of Edinburgh, UK
- Kelda Chia, Marcus Keatinge, Julie Mazzolini and Dirk Sieger. Brain tumours repurpose endogenous neuron to microglia signalling mechanisms to promote their own proliferation. eLife; 2019 Jul 17;8.
- Julie Mazzolini, Sigrid Le Clerc, Cédric Coulonges, Jean-François Zagury and Dirk Sieger. Gene expression profiling reveals a conserved microglia signature in larval zebrafish microglia. Glia, Sep 11. doi: 10.1002/glia.23717. [Epub ahead of print]
- Catherine Adam, Ana M. Pérez-López, Lloyd Hamilton, Belén Rubio-Ruiz, Thomas L. Bray, Dirk Sieger, Paul M. Brennan and Asier Unciti-Broceta. Bioorthogonal Uncaging of the Active Metabolite of Irinotecan by Palladium-Functionalized Microdevices. Chemistry 2018; November 13;(24)63:18783-16790.
- Mazzolini J, Chia K, Sieger D. Isolation and RNA Extraction of Neurons, Macrophages and Microglia from Larval Zebrafish Brains. J. Vis. Exp. (134), 2018; doi:10.3791/57431
- Chia K, Mazzolini J, Mione M, Sieger D. Tumor initiating cells induce Cxcr4 mediated infiltration of pro-tumoral macrophages into the brain. eLife; 2018 Feb 21;7
- Killick J, Morisse G, Sieger D, Astier AL. Complement as a regulator of adaptive immunity. Seminars in Immunopathology; 2017 Aug 23;:1–12.
- Pérez-López AM, Rubio-Ruiz B, Sebastián V, Hamilton L, Adam C, Bray TL, Irusta S, Brennan PM, Lloyd-Jones G, Sieger D, Santamaria S and Unciti-Broceta A. Gold-Triggered Uncaging Chemistry in Living Systems. Angew Chem Int Ed. 2017 Jul 12.
- Mayrhofer M, Gourain V, Reischl M, Affaticati P, Jenett A, Joly JS, Benelli M, Demichelis F, Poliani PL, Sieger D and Mione M. (2017) A novel brain tumour model in zebrafish reveals 1 the role of YAP activation in 2 MAPK/PI3K induced malignant growth. Disease Models and Mechanisms. 2017 Jan 1; 10(1):15-28
- Astell KR and Sieger D. (2017) Investigating microglia-brain tumor cell interactions in vivo in the larval zebrafish brain. Methods Cell Biol. 2017; 138:593-626
- Hamilton L, Astell KR, Velikova G, Sieger D. (2016) A Zebrafish Live Imaging Model Reveals Differential Responses of Microglia Toward Glioblastoma Cells In Vivo. Zebrafish. 2016 Oct 25
- Ohnmacht J, Yang Y, Maurer GW, Barreiro-Iglesias A, Tsarouchas TM, Wehner D, Sieger D, Becker CG, Becker T. (2016) Spinal motor neurons are regenerated after mechanical lesion and genetic ablation in larval zebrafish. Development. 2016 May 3;143(9):1464–74.
- 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: 1331–1346.
- Sieger D. and 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. and Peri F. (2012) Long-range Ca2+ waves transmit brain damage signals to microglia. Dev Cell. 2012 Jun 12; 22(6):1138-48.(* authors contributed equally)
- Böcke A.*, Sieger D.*, Kashkar H., Krönke M. (2012) FAN mediates navigational capacity of macrophages responding to wounds and infection- live imaging studies in zebrafish larvae. J Immunol. 2012 Aug 15;189(4):1559-66 (* authors contr. equally)
- Aggad D, Stein C, Sieger D, Mazel M, Boudinot P, Herbomel P, Levraud JP, Lutfalla G, Leptin M. (2010).In vivo analysis of Ifn-γ1 and Ifn-γ2 signaling in zebrafish. J Immunol. Dec 1;185(11):6774-82
Key Earlier Publications
- 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. Disease Models & Mechanisms. Nov-Dec;2(11-12):571-81
- Aggad D, Stein C, Sieger D, Mazel M, Boudinot P, Herbomel P, Levraud JP, Lutfalla G, Leptin M. (2010). In Vivo Analysis of Ifn-γ1 and Ifn-γ2 Signaling in Zebrafish. The Journal of Immunology. Dec 1;185(11):6774-82
- Shankaran S.*, Sieger D.*, Schröter C., Czepe C., Pauly M.C., Laplante M.A., Becker T.S., Oates A.C., and Gajewski M. (2007). Completing the Set of h/E(spl) Cyclic Genes in Zebrafish: her12 and her15 Reveal Novel Modes of Expression and Contribute to the Segmentation Clock. Developmental Biology. 304(2), 615-32. *Authors contributed equally.
- Gajewski M., Elmasri H., Girschick M., Sieger D. and Winkler C. (2006). Comparative Analysis of her Genes during Fish Somitogenesis Suggests a Mouse/Chick-Like Mode of Oscillation in Medaka. Development Genes and Evolution. 216(6), 315-32.
- Sieger D., Ackermann B., Winkler C., Tautz D. and Gajewski M. (2006). her1 and her13.2 are Jointly Required for Somitic Border Specification Along the Entire Axis of the Fish Embryo Developmental Biology. 293(1), 242-51.
- Sieger D., Tautz D. and Gajewski M. (2004). her11 is involved in the somitogenesis clock in zebrafish. Development Genes and Evolution. 214, 393-406.
- Sieger D., Tautz D. and Gajewski M. (2003). The Role of Suppressor of Hairless in Notch Mediated Signalling During Zebrafish Somitogenesis. Mechanisms of Development. 120, 1083-94.
- Gajewski M.*, Sieger D.*, Alt B., Leve C., Hans S., Wolff C., Rohr K. B. and Tautz D. (2003). Anterior and Posterior Waves of Cyclic her1 Gene Expression are Differentially Regulated in the Presomitic Mesoderm of Zebrafish. Development 130, 4269-78. *Authors contributed equally.