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:
1) What are the endogenous and exogenous noncoding RNA species that contribute to innate immune modulation and how are these functions mediated?
2) How does the cell intrinsic innate immune system shape the γ-herpesviral lifecycle and what are the host and viral entities at play?
3) What is the contribution of endogenous retroviruses and transposons to the host-virus interaction?