Alla Piirsoo

Research:

Human papillomaviruses (HPVs) are small viruses with a double-stranded circular DNA genome infecting either skin or mucosal epithelium. More than 200 different HPV types have been described to date. Most HPV infections are asymptomatic and harmless for the host organism. However, there are also tumorigenic HPVs, which are responsible for about five percent of all cancers worldwide. Nowadays, HPV is considered as one of the most prominent infectious risk factors associated with many different types of cancers, such as cervical, anogenital, and head and neck cancers. Despite the fact that vaccines are available to prevent HPV infections, they have been developed only against a small number of different HPV types and are ineffective against ongoing infections. Therefore, the HPV-related medical problems remain to stay in the foreseeable future.

HPV infection and replication are restricted to a small number of host cell types, and rely on the utilization of the specific host cell proteins. Our research group studies the mechanisms of HPV genome replication with a wider goal to propose novel therapeutic methods or targets to supress the extent of the ongoing viral infection.

In particular, we focus on:

• studying the post-translational modifications of the HPV replication proteins E1 and E2. These proteins are the only viral trans-factors necessary for the HPV genome replication. They both are regulated by the activities of the host cell proteins. We have identified several protein kinases, including CK2 and PKA, that phosphorylate either E1, E2 or both. Furthermore, we have shown that depending on the HPV type, E1 and E2 phosphorylation by some protein kinases can have antagonistic phenotype. Currently, we are in the process of identifying mechanistic differences in the regulation of the E1 and E2 proteins of both mucosa and skin infecting HPV types, which have clear phenotype in the HPV genome replication.
• screening small molecular weight chemical libraries to identify novel compounds that inhibit HPV replication.
• investigating the roles of some host cell transcription factors (mainly from GLI and POU-HD families) and DNA repair pathways involved in the regulation of the HPV replication and tropism.

Team:

Bachelor's student

Nika Mikhailava  

Master's student

Ruslan Ibragimov

PhD student

Elina Lototskaja

Laboratory technicians

Sofiya Babok 

Regina Pipitš

Associate professor

Marko Piirsoo

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