Using synthetic virology approaches to elucidate novel virus-host interactions and develop targeted therapeutics

The central theme of my research program will study poxvirus-host cellular interactions to develop effective and more personalized biotherapeutics (vaccines and oncolytic viruses [OVs]) towards cancers and infectious diseases using synthetic virology approaches. I am interested in harnessing the power of these technologies to study how cellular antiviral responses are differentially induced in various cell types during poxvirus infections. I am also interested in the relationship between nucleic acid sensing pathways and other poxvirus biological processes (like transcription, replication, and recombination). I plan to extend these studies to investigate the role of known and unknown viral antagonists of nucleic acid sensing on these processes. I will use my skills in rapidly generating recombinant poxviruses using synthetic biology technologies to discover what makes viruses able to replicate efficiently in some cell types, and not others. Understanding why poxviruses preferentially replicate in certain cell types or species will enhance their utility as cancer therapeutics. Results from these basic molecular virology studies will inform my studies on generating more potent OVs, whether alone, or in combination with other treatment modalities, like adoptive cell therapies, radiation, or in combination with OVs from unrelated virus families. I am also interested in whether these modified viruses can be used as vaccines to increase the magnitude and durability of an immune response to emerging/re-emerging viruses, including monkeypox virus and SARS-CoV-2.