Ao.Univ. Prof. Dr. Rainer de Martin

work address

Department of Vascular Biology and Thrombosis Research
Centre of Physiology and Pharmacology
Schwarzspanierstrasse 17, 1090 Vienna, Austria

Phone: +43 (0)1 40160 - 31161

E-Mail: rainer.demartin@meduniwien.ac.at

Jomepage: http://www.meduniwien.ac.at/user/rainer.demartin/
 

Know-how and research interests

Our general aim is the elucidation of molecular mechanisms of inflammation in vascular, mostly endothelial cells. Model systems are mostly HUVEC that are stimulated with pro-inflammatory cytokines (TNFa, IL-1) or LPS. Main questions are:

a. which genes are expressed during the inflammatory response ?

b. how is their expression regulated ?

c. how is the inflammatory reaction resolved/terminated ?

Work in the past has focused on the first two questions, resulting in a broad overview over the genetic response in EC to inflammatory stimuli (Mayer 2004), and to the identification of the transcription factor NF-kB as a main regulator of many of these genes, including in vivo proof-of-concept studies (Breuss 2002, Cejna 2002, Trescher 2003, Kopp 2004).

Presently, our main focus is on the concept of negative feedback mechanisms: this is based on the observation that upon inflammatory stimulation EC do not only express genes that are associated with the execution of inflammatory process (e.g., cell adhesion molecules, interleukins, etc,..) but also proteins with inhibitory function, the most prominent example being IkBa, the inhibitor of NF-kB that shuts down NF-kB activity at later times. Thus, we hypothesize that already at early time points after stimulation EC set the stage for the later resolution of the inflammatory response. In our experiments, approx. 10% of all upregulated genes following IL-1 stimulation have potentially inhibitory function. At present, we have chosen tristetraproline, a RNA-destabilizing protein with additional inhibitory activity towards NF-kB and JNK signaling, for our current studies (Schichl 2009, 2011).

Other topics studied in the lab include the role of Etr101/IER2 another example of a negative feedback regulator, and the role of the transcription factor Sox18 in angiogenesis. 

Research topic

Molecular mechanisms of inflammation

Techniques and infrastructure of the research group

All basic molecular and cellular biology techniques, specialized techniques for analysis of transcriptional regulation (EMSA, ChIP, reporter gene assays,…), signal transduction (co-ip, kinase assays,…), ubiquitination assays.

5 selected publications

Mayer, H., Bilban, M., Kurtev, V., Gruber, F., Wagner, O., Binder, B.R., and de Martin, R. (2004) Deciphering Regulatory Patterns of Inflammatory Gene Expression from Interleukin 1 - Stimulated Human Endothelial Cells. Arterioscler. Thromb. Vasc. Biol. 24(7):1192-8.

Winsauer, G., Resch, U., Schichl, Y., Hofer-Warbinek, R., and de Martin, R. (2008) XIAP regulates bi-phasic NF-kB induction involving physical interaction and ubiquitination of MEKK2. Cell Signaling 20:2107-2112.

Wiesner, C., Winsauer, G., Resch, U., Hoeth, M., Schmid, J.A., van Hengel, J., van Roy, F., Binder, B.R., and de Martin, R. (2008) a-Catulin, a Rho signaliing component, can regulate NF-kB through binding to IKK-ß, and confers resistance to apoptosis. Oncogene 27(15):2159-2169.

Schichl, YM., Resch, U., Hofer-Warbinek, R., de Martin, R. (2009). Tristetraprolin impairs p65/RelA nuclear translocation. J. Biol. Chem. 284(43):29571-81.

Schichl, YM, Resch, U, Lemberger, CE, Stichlberger, D, and de Martin, R. (2011) Novel phosphorylation-dependent Ubiquitination of Tristetraprolin by MEK kinase 1 (MEKK1) and TNF-receptor associated factor 2 (TRAF2). J. Biol. Chem. 286(44):38466-77