Molecular Diagnostics of Oncogenic Infections

Division of Molecular Diagnostics of Oncogenic Infections

Dr. Michael Pawlita(in ch.)

Papilloma viruses seen through an electron microscope: Surface proteins play a crucial role in research towards novel vaccines
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Our aim is the identification of human papil¬lomaviruses (HPV) and other viruses and bac¬teria as causal factors in the pathogenesis of specific cancer entities where this has as yet not been reliably demonstrated (1). We have developed a high-throughput platform for si¬multaneous detection of arrays of human an¬tibodies or nucleic acids, which we use to analyze large sample collections from collab¬orative epidemiological studies. We also ex¬plore biomarkers as predictors for infection-in¬duced cancers, such as HPV mRNA patterns for early detection of cervical cancer, antibodies to HPV early proteins in oropharyngeal cancer (2), and antibody patterns to Helicobacter species in gastric and other gastrointestinal cancers. We further investigate the potential of an HPV vaccine to prevent recurrence of genital warts.
Studies on cellular APOBEC3 cytidine deami¬nase restriction factors and their dynamic co¬evolution with foamy viruses (3) led to iden¬tification and characterization of APOBEC3 mutation signatures in diverse cancers. The contribution of APOBEC3 activity and genome mutations caused by APOBEC3 to infection-and inflammation-mediated oncogenesis are currently investigated. We also study the role of lipoxygenases (LOX) in epidermal development, homeostasis and cancer (4). Current studies are aimed to deci¬pher the implication of LOX in the pathogene¬sis of the inherited skin disease ichthyosis and to develop novel therapeutic approaches.

FUTURE OUTLOOK
Several planned seroepidemiological studies will determine prevalences of multiple, pre¬dominantly oncogenic infectious agents in German and other European populations, and risk factors for these infections. A number of ongoing studies aim at analyzing genetic de¬terminants of infection susceptibility and im¬mune response. Infection markers with diag-nostic or prognostic value will be clinically val¬idated.

The contribution, mechanisms and control of APOBEC3-driven mutagenesis to oncogenesis will be analyzed in vitro and in animal models as well as patient-derived specimens. In addi¬tion, the mode of action and future exploita¬tion of the foamy virus Bet protein as a natural and specific inhibitor of APOBEC3 as well as vi¬rus-expressed miRNAs will be studied.

Contact

Dr. Michael Pawlita (in ch.)
Molecular Diagnostics of Oncogenic Infections (F020)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 242
69120 Heidelberg
Tel: +49 6221 42 46 03
Fax: +49 6221 42 49 32

Selected Publications

  • Halec G. et al. (2014). Pathogenic role of the eight probably/possibly carcinogenic HPV types 26, 53, 66, 67, 68, 70, 73 and 82 in cervical cancer. J Pathol, 234(4), 441–451.
  • Kreimer A.R. et al. (2013). Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer. J Clin Oncol, 31(21), 2708–2715.
  • Lukic D.S. et al. (2013). Identification of the feline foamy virus Bet domain essential for APOBEC3 coun¬teraction. Retrovirology, 10:76.
  • Krieg P. & Fürstenberger G. (2014). The role of li¬poxygenases in epidermis. Biochim Biophys Acta, 1841(3), 390–400.
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