Functional analyses of cervical cancer pathogenesis and development of antiviral substances
Cervical cancer is the second most common cancer among women with a world- wide prevalence of 2,27 millions and with an estimated 490,000 new cases and
270,000 deaths per year. “High risk” human papillomaviruses are detected in over 98% of cervical carcinoma cases. Together with Prof. Dr. Peter Howley (Harvard Medical School, Boston) we have found that the interaction between the viral E2 protein and the cellular bromodomain containing protein Brd4 is required for the genome maintenance and the viral transcriptional regulation functions and thereby regulate cervical cancer pathogenesis. We are now working on specific inhibitors of this interaction and we are using NGS technologies for an investigation of functional consequences for cervical cancer pathogenesis. Our experiments show that a disruption of the interaction between E2 and Brd4 leads to a curing of cells from papillomavirus infections and thereby might prevent cervical cancer.
Brd4 with its two bromodomains binds to acetylated histones, pTEFb (positive transcription elongation factor) and is dealt as master regulator of the epigen- etic memory. We have found that Brd4 plays a significant role in transcriptional regulation, but that it is also a central partner in the oxidative stress response. Preliminary experiments indicate that an epigenetic regulation of the defense mechanisms against reactive oxygen species functions over histone methylations.
Taken together, the goals of the Cancer Genomics Group are to integrate different fields of medicine, biology and natural science in order to better understand how tumor cells work and how carcinogenic processes are regulated. Knowledge of disease- relevant alterations in gene sequences and molecules of the metabolic network will reveal targets for effective diagnostic and therapeutic applications. With the availability of these techniques we are on a turning point of cancer di- agnosis and treatment.