This research cluster project addresses the role of TTP (tristetraprolin) and HuR, two key factors controlling mRNA turnover, in inflammatory bowel disease (IBD) and inflammation-associated colon cancer (colitis-associated cancer, CAC). IBD arises by a so far unknown mechanism causing erroneous inflammatory responses in the intestinal tissues. The chronic intestinal inflammation in IBD can drive the development of CAC. Currently the most promising strategies for IBD and, consequently, CAC treatment appear to be approaches aiming at the suppression of inflammation in the affected tissues. The mRNA-binding proteins TTP and HuR appear suitable yet so far not exploited candidates for novel therapies. Both proteins regulate the production of multiple cytokines by controlling the cytokine mRNA stability. In general, HuR is regarded as a stabilizing and TTP as a destabilizing factor.

The project asks (i) whether a dysregulated function of TTP and HuR has a causal role in the onset and progression of IBD and CAC, and (ii) whether genetic or pharmacological targeting of TTP and HuR helps restoring normal tissue and immune homeostasis.

The project employs animal models and human tissue analyses to address the basic principles of the function of TTP and HuR in the selected diseases, and to provide insights into the future exploitation of mRNA turnover in therapies of human diseases.

The mRNA-stabilizing protein HuR is upregulated in many tumor cells:

HuR expression in colon (1) and adjacent tumor tissue (2)

Contact:

Ao.Univ.-Prof. Dr.med.univ. Christoph Gasche
Universitätsklinik für Innere Medizin III
Christian Doppler Labor für Molekulare Karzinom Chemoprävention
Medizinische Universität Wien
christoph.gasche@meduniwien.ac.at

http://www.meduniwien.ac.at/innere3/gaschelab/

Univ.-Prof. Dr. Pavel Kovarik
Max F. Perutz Laboratories
Universität Wien
Pavel.kovarik@univie.ac.at

http://www.mfpl.ac.at/mfpl-group/group/kovarik.html