Research Projects
Table of Contents
I. ONCOVIRUSES
By conservative estimation, tumor viruses are linked to 15-20% of human cancers. Viruses thus are second most common defined risk factor for cancer development in humans (exceeded only by smoking).
It is one of the major interests in our laboratory to elucidate the molecular mechanisms by which tumor viruses lead to oncogenic transformation.
Tumor viruses, such as HPVs, typically attack cellular pathways which are altered in many other cancers by alternative mechanisms (e.g. by somatic mutations). Thus, the elucidation of critical cellular pathways targeted by tumor viruses will not only be informative for tumor virology but should also provide us with novel insights into generally relevant mechanisms of carcinogenesis.
The understanding of the activities of viral oncogenes and their targets is also a pre-requisite for the development of novel therapeutic strategies. Consequently, a second major topic in the laboratory is the development of specific inhibitors (siRNAs, inhibitory peptides, small molecules) blocking viral and cellular proteins which contribute to carcinogenesis (“targeted therapy”).
1. Human Papillomaviruses (HPV)
HPVs are closely related to the development of several cancers, including cervical cancer which is the second most common cancer in females worldwide. In addition, a role for HPVs in the development of skin cancer is discussed.
Ongoing projects:
- Targeted inhibition of the HPV E6 and E7 oncoproteins by inhibitory peptides and small molecules
- Delineation of downstream cellular targets for the viral oncogenes.
- Identification of novel molecular markers and therapeutic targets for cervical cancer.
II. CONTROL OF TUMOR CELL PROLIFERATION AND APOPTOSIS
We are also interested in analyzing cellular proteins implicated in the growth and apoptosis control of tumor cells. They include factors which are preferentially expressed in tumors, such as the anti-apoptotic Livin gene, and therefore may constitute interesting novel therapeutic targets. In addition, we focus on cellular targets of HPVs (EZH2, BTG2, others) which are critical for the oncogenic phenotype.
1. Livin
Livin is a member of the “Inhibitor of Apoptosis (IAP)” protein family and may contribute to the resistance of cancer cells towards chemo- and radiotherapy.
Ongoing projects:
- Targeting of Livin for functional inactivation by peptides and siRNAs.
- Molecular analysis of apoptosis inhibition by Livin.
- Clinical cooperations to investigate the status of Livin in different tumor entities.
2. Novel Cellular HPV Targets
As discussed above, the viral E6 and E7 oncogenes represent valuable tools to study human carcinogenesis. For example, we observed that E7 activates the proliferative EZH2 gene and E6 suppresses the BTG2 tumor suppressor gene – both genes play a role in many cancers and may serve as novel tumor markers. Current work also focuses on another cellular gene which is activated by oncogenic HPVs and plays a major role for the growth/survival of HPV-positive cancer cells.
Ongoing projects:
- Functional analysis of novel cellular HPV targets in cervical cancer cells.
- Clinical cooperations to investigate their status in different tumor entities.
- Targeted inhibition of cellular HPV targets by inhibitory peptides and small molecules.
