Antiviral and anticancer research

Projects

Influence of human cytomegalovirus on tumor progression

Infection with human cytomegalovirus (HCMV) is very common in the population. Although the virus does not possess ability to transform normal cells (like classical tumor viruses), infection of already existing tumor cells with HCMV can increase the malignancy of the tumor (so called oncomodulation). Simultaneously, the efficacy of chemotherapeutic drugs is strongly decreased.
In our lab, we investigate the effects of HCMV infection and specific viral genes of HCMV on proliferation, cell cycle, apoptosis and angiogenesis of the tumor cells. It is possible that oncomodulatory effects are also excerted by viruses other than HCMV. Understanding the mechanisms that lead to oncomodulation is crucial for the development of new anti-tumor therapies, using combination of antiviral and antitumoral drugs.

Antiviral therapy

We have developed cell culture models of respiratory viruses and herpes viruses which enable us to test different substances for their antiviral potency. This tool helped us to identify novel substances against e.g. Cytomegalovirus (desferol and sorafenib)

We also found effective substances against emerging highly pathogenic respiratory viruses like SARS-CoV (glycyrrhizin) or avian influenza H5N1 strains (natural substances like flavonoids or polyterpens).

Currently, a panel of 1443 US FDA (Food and Drug administration) approved drugs is tested for antiviral activity against HCMV and measles. For both viruses, we already identified some substances with antiviral activity.

Establishment and maintenance of a drug-resistant cancer cell line collection

Chemotherapy is often limited by development of chemoresistance in tumor cells (failure of therapy). A few commercial bioresource centers are already existing (e.g. NCI-60, JCFR-39, CMT1000), but these cell line collections do not contain chemoresistant tumor cells. For better understanding of the underlying mechanisms of chemoresistance and for the development of new therapy strategies, chemoresistant cancer cell in vitro -models are essential.  Over the years, we have established a unique collection of resistant cancer cell lines (RCCL collection: http://www.kent.ac.uk/stms/cmp/RCCL/RCCLabout.html). The resistant cancer cell lines were gradually adapted over a longer perid of time to grow in the presence of one specific drug. Classical chemotherapeutic drugs were used in this adaptation process, as well as new compounds (targeted cancer therapeutics). Currently, the RCCL collection consists of more than 1,500 chemoresistant cancer cell lines with over 50 different drugs used for adaptation. Some of the resistant cancer cell lines are also established as xenografts in nude mouse model.

Apart from generating chemoresistant cell lines, we also have expertise in establishing cell lines out of biopsy material or primary probes, both of pediatric and adults patients.

Investigation of molecular chemoresistance mechanisms in tumor cells

Cell lines from the RCCL collection are used for studying the resistance mechanisms that led to failure of therapy. Some cell lines from the RCCL collection have already been used in an international project funded by the European Commission (EU-project “SYNLET”) and are currently used in a project sponsored by “Deutsche José Carreras Leukämie-Stiftung e.V.”. Cell lines from the RCCL collection are used by many collaborators all over the world and are therefore part of many publications in the field of cancer research.

SAMHD1

In the context of chemoresistance mechanisms against nucleoside analogs, we discovered SAMHD1 as a novel resistance factor and possible biomarker in AML (acut