Oncogenic Viruses, RNA-based mechanisms of antiviral and antitumor immunity, epigenomics, CRISPR screens
The association between infection with viruses and neoplasia is well established for a variety of cancers. In fact, approximately 12% of human cancers worldwide are caused by oncogenic viral infections, with more than 80% of cases occurring in the developing world. Despite their prevalence and public health importance, our understanding and ability to manage viral-induced cancers is still limited. This is in part due to the complexity of host-virus interactions leading to cellular transformation. Research in our laboratory is focused on defining the host-virus interaction in the context of gammaherpesviral infection. γ-herpesviruses, which include the human oncogenic viruses Kaposi Sarcoma-associated herpesvirus (KSHV) and Epstein Barr virus (EBV), are a family of large double-stranded DNA lymphotrophic viruses that are the causative agents of a variety of disorders, including lymphoproliferative diseases, lymphomas, as well as other nonlymphoid cancers in mammals. Studies of the host response to viral infection have historically focused on protein-coding genes, thus our understanding of how the non-protein-coding transcriptome, including both viral- and host-derived noncoding RNAs, impacts host-virus interactions is limited. Along this line, our primary research goals are directed towards understanding how noncoding RNAs and their RNA-binding proteins are integrated in to the regulation of gene expression and modulation of the host immune response during γ-herpesviral infection. To accomplish this we undertake a multidisciplinary approach combining virology, immunology, RNA biochemistry, proteomics, and genomics/transcriptomics. Major thematic questions of the lab include:
- What are the endogenous and exogenous noncoding RNA species that contribute to innate immune modulation and how are these functions mediated?
- How does the cell intrinsic innate immune system shape the γ-herpesviral lifecycle and what are the host and viral entities at play?
- What is the contribution of endogenous retroviruses and transposons to the host-virus interaction?