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Division of Viral Transformation Mechanisms

Prof. Dr. Frank Rösl

A) Induction of autophagy (red) in HPV immortalized human keratinocytes (blue: stained nuclei). B) Mitochondria staining in primary keratinocytes (Green)
Courtesy of Dr. B. Rincon Orozco (F030)
© dkfz.de

Genital human papillomaviruses (HPVs) account for 99% of cervical cancers. Although vaccines against these HPV types are currently available, the exact mechanisms by which these viruses contribute to carcinogenesis are still not fully understood. In order to find preventive as well as therapeutic options, the relationships and interactions between the virus and the host cell must be clearly understood. In this context we are interested in the signal transduction pathways in which papillomaviruses interfere and how they change under certain conditions (e.g., after further infection with bacteria or under nutrient or oxygen deprivation).

Another focus is the relationship between "white" skin cancer and the infection with so-called cutaneous papilloma viruses. Although they are suspected - in conjunction with excessive sun exposure or under immune suppressive conditions - to promote the development of non-melanoma skin cancer, there are still no vaccines available. This is not least due to a lack of suitable preclinical model systems that reflect the situation in humans and in which such vaccines can be tested. In order to investigate these questions, suitable preclinical models are necessary. Only in this way other risk factors such as UV exposure and/or immunosuppression can be included and tested in the context of an entire organism.

The rodent Mastomys coucha represents such a model as it allows the analysis of basic mechanisms of papillomavirus-induced skin carcinogenesis. In this rodent that is infected with cutaneous papillomaviruses, the entire pathogenesis, starting from the first infection to the final development of skin tumors can be examined, both in immunologically and molecular biological terms. Here we have already developed a vaccine against papillomavirus-induced skin tumors which is completely protective even under immunosuppressive conditions. In addition, we are currently investigating how UV radiation in conjunction with a viral infection affects the genesis of skin tumors.

Contact

Prof. Dr. Frank Rösl
Viral Transformation Mechanisms (F030)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 4900

Selected Publications

  • Hasche D, Stephan S, Braspenning-Wesch I, Mikulec J, Niebler M, Gröne H-J, Flechtenmacher C, Akgül B, Rösl F, and Vinzón SE (2017). The Interplay of UV and Cutaneous Papillomavirus Infection in Non-Melanoma Skin Cancer Development in the animal model Mastomys coucha. PLoS Pathog 13(11): e1006723. doi: 10.1371/journal.ppat.1006723
  • Higareda-Almaraz JC, Ruiz-Moreno JS, Klimentova J, Barbieri D, Salvador-Gallego R, Ly R, Valtierra-Gutierrez IA, Dinsart C, Rabinovich GA, Stulik J, Rösl F, Rincon-Orozco B. (2016). Systems-level effects of ectopic galectin-7 reconstitution in cervical cancer and its microenvironment. BMC Cancer. 2016 Aug 24;16:680. doi: 10.1186/s12885-016-2700-8.
  • Niebler, M., Qian, X., Höfler, D., Kogosov, V., Kaewprag, J., Kaufmann, A.M., Ly, R., Böhmer, M., Zawatzky, R., Rösl, F., and Rincon-Orozco, B. (2013). Post-Translational Control of IL-1? via the Human Papillomavirus Type 16 E6 Oncoprotein: A Novel Mechanism of Innate Immune Escape Mediated by the E3-Ubiquitin Ligase E6-AP and p53. PLoS Pathogens, DOI: 10.1371/journal.ppat.1003536.
  • Vinzon, S.E., Braspenning-Wesch, I., Müller, M., Geissler, E.K., Nindl, I., Gröne, H-J., Schäfer, K., and Rösl, F. (2014). Protective Vaccination against Papillomavirus-Induced Skin Tumors under Immunocompetent and Immunosuppressive Conditions: A Preclinical Study Using a Natural Outbred Animal Model. PLoS Pathogens, Feb 20; 10 (2): e1003924.
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