Division of Viral Transformation Mechanisms
Prof. Dr. Frank Rösl

1. Mechanisms of human papillomavirus (HPV)-induced carcinogenesis:
Here we are investigating how transcription and viral RNA splicing of high-risk HPV is regulated during the different steps towards malignant transformation. Another focus is the function of epigenetic mechanisms (e.g. de novo methylation, nucleosomal organisation, micro-RNAs) in HPV-positive cells and their impact on viral-host interaction during persistence.
2. Immunological surveillance:
In this context, we are studying the interferon/chemokine pathway to understand the innate response against a viral infection. Moreover, referring to the role of inflammation and cancer, we are examining the function of individual HPV oncoproteins on the NALP3 inflammasome.
3. A natural rodent model system for papillomavirus (PV)-induced skin cancer:
In this project we study the whole infection pathway, starting from primary infection till the final manifestation of a skin tumor in molecular and serological terms. We have also developed a “virus-like particle” (VLP) based vaccine to prevent PV-induced skin lesions. This vaccine is currently tested under normal and immunocomprimized conditions.
4. Virus-Cell Interactome
Considering a cell as a functional regulatory network, tumorviruses always attack central hubs to overcome intracellular surveillance. It is therefore necessary to understand these viral-host interactions using systems biology approaches.
Selected Publications
Darvas, K., Brenner, D., Fritsch, C., Gmelin, N., Krammer, P.K., and Rösl, F. (2010). HDAC inhibitor-induced sensitisation to TNF/TRAIL-mediated apoptosis in cervical carcinoma cells is dependent on HPV oncogene expression. International Journal of Cancer, 127, 1384-1392
Rincon-Orozco, B., Halec, G., Rosenberger, S., Muschik, D., Nindl, I., Bachmann, A., Ritter, T.M., Dondog, B., Ly, R., Bosch, F.X., Zawatzky, R., and Rösl, F. (2009). Epigenetic silencing of interferon-? in human papillomavirus type 16 positive cells. Cancer Research, 69, 8718-8725
Rosenberger, S.J., De-Castro, J., Langbein, L., Steenbergen, R., and Rösl, F. (2010). Alternative splicing of HPV16 E6/E6* early mRNA is coupled to EGF-signalling via Erk activation. Proc. Natl. Acad Sci. U.S.A., 107, 7006-7011
Schäfer, K., Neumann, J., Waterboer, T., and Rösl, F. (2011). Serological markers for papillomavirus infection and skin tumour development in the rodent animal model Mastomys coucha. Journal of General Virology, 92, 383-394