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
© dkfz.de

The aim of the groups of Tim Waterboer and Michael Pawlita is the investigation of human papillomaviruses (HPV), other viruses and bacteria as etiological factors in the pathogenesis of specific cancer entities where this has, as yet, not been reliably demonstrated. We have developed a high-throughput platform for simultaneous detection of arrays of human antibodies or nucleic acids which we use to analyze large sample collections from collaborative epidemiological studies. We also explore biomarkers as predictors for infection-induced cancers, such as HPV mRNA patterns for the detection of cervical cancer precursors, antibodies to HPV early proteins to identify individuals at high risk for development of oropharyngeal cancer, and antibody patterns to Helicobacter species as well as other bacteria in gastric and other gastrointestinal cancers. We further investigate the potential of an HPV vaccine to prevent recurrence of genital warts.

Studies of Martin Löchelt’s group on cellular APOBEC3 cytidine deaminase restriction factors and their dynamic coevolution with foamy viruses led to the identification 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 being investigated.

The group of Peter Krieg studies the role of lipoxygenases (LOX) in epidermal development, homeostasis and cancer. Current projects aim to decipher the implication of LOX in the pathogenesis of the inherited skin disease ichthyosis and to develop novel therapeutic approaches.

OUTLOOK

Several seroepidemiological studies will determine prevalences of multiple, predominantly oncogenic, infectious agents in German and other European populations, as well as risk factors for these infections. A number of ongoing studies aim at analyzing genetic determinants of infection susceptibility and immune response. Infection markers with diagnostic or prognostic value will be clinically validated.

The contribution, mechanisms and control of APOBEC3-driven mutagenesis in human cancers will be analyzed in vitro and in patient-derived specimens. As a new line of research, the mechanisms targeting the foamy virus pre-integration complex to the chromatin leading to a favorable integration profile with respect to insertional mutagenesis 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

  • Sankaranarayanan R. et al. (2016) Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre prospective cohort study. Lancet Oncol 2016; 17: 67–77.
  • Kreimer A.R. et al. (2017). Kinetics of the Human Papillomavirus Type 16 E6 Antibody Response Prior to Oropharyngeal Cancer. , J Natl Cancer Inst 109(8): djx005.
  • 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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