Our scientific question is how viruses promote cancer development.
The research interests in the lab are to study the functional interactions between viral proteins and the cellular machinery, which control both the viral life cycle and tumorigenesis. About 15% of the cancers in humans are associated with viral infections. The viruses we study are the human gamma herpes viruses; Kaposi’s sarcoma associated herpesvirus (KSHV, HHV-8) and Epstein-Barr virus (EBV, HHV-4) that are associated with increasing number of human malignancies. EBV is a ubiquitous virus that infects over 90% of adults worldwide, including Israel. KSHV prevalence varies significantly depending on the geographic regions; in Israel about 10% are infected. While in the majority of infected individuals these viruses do not lead to cancer development, under specific condition such as suppression of the immune system they promote cancer development. The goal of our lab is to expand our knowledge on viral infections, and to utilize this knowledge for the development and use of drugs that specifically target virally infected cells.
I have specific interest to understand how these viruses modulate our epigenome. Epigenetic marks such as DNA methylation, histone modifications and chromatin remodeling are important regulators of gene expression. Together with genetic alterations, epigenetic modifications are responsible for the development of many diseases, including cancer. In agreement with this concept, all human viruses that are associated with tumor development alter the human epigenome. Previously I have found that the KSHV encoded LANA protein leads to CpG DNA methylation by interacting with the cellular de-novo DNA methyltransferase, DNMT3a, and recruiting DNMT3a to certain promoters that become methylated and repressed.
Examples of scientific questions we ask:
1. What are the global epigenetic changes these viruses impose on infected cells?
2. Which epigenetic marks differentiate infected cell from infected cell that become cancerous? The results of these studies will help us to develop novel methods for the detection of viral associated malignancies.
3. Recently, I have found that KSHV encoded LANA leads to telomere shortening. We will try to understand how LANA regulates telomere length.
4. After reading the above, if you have a scientific question related to our study let’s talk about your next project.