A remarkable hallmark of all herpesviruses is the propensity to establish a life-long persistent infection in the presence of active immune responses. Presumably, these pathogens have evolved intricate strategies to evade and exploit host immune responses. Innate immunity is the first line of defense against pathogen infection. Our group is keen on studying the means by which human Kaposi’s sarcoma-associated herpesvirus and its close relative, murine gamma herpesvirus 68, manipulate cellular innate immune signaling pathways. We are also interested in defining viral factors and cellular components that collectively contribute to the inflammation-driven oncogenesis invoked by human lymphotropic herpesviruses. With modern molecular virology, biochemical, and genetic approaches, we are employing mouse models to dissect the molecular events of the innate immune signaling cascades underlying virally-induced tumorigenesis. The long-term goal of the Feng lab is to develop new strategies that treat infection- and inflammation-associated human malignancies.

Currently, there are two main projects conducted in the Feng laboratory.

One project is to interrogate the dynamic regulation of host innate immune signaling pathways, specifically those downstream of the pattern recognition receptors, by gamma herpesviruses during infection. Our recent studies have uncovered that murine gamma herpesvirus activates an innate immune signaling pathway to enable viral transcriptional activation and disable host antiviral gene expression, thereby effectively promoting viral lytic replication. Ongoing research in our lab focuses on characterizing virus-host interactions and signal transduction thereof that instigate cellular innate immune activation. Our findings will establish a new precedent whereby host innate immune activation is exploited to promote viral replication.

The other project is guided by the concept that innate immune signaling pathways are key determinants for chronic inflammation, an integral pathological feature of diverse human malignancies ranging from life-threatening cancers to disfiguring obesity. Employing mouse models of xenograph, gene knockout, and endothelium-targeted gene delivery, we are determining whether innate immune signaling pathways, downstream of cytosolic sensors and Toll-like receptors, are important for inflammatory malignancies, including Kaposi’s sarcoma and obsesity. We are also developing a new mouse model that truthfully recapitulates oncogenesis (lymphomagenesis or sarcomagenesis) in individuals infected by human gamma herpesviruses. These animal models will provide useful tools to analyze key steps of inflammation-driven tumorigenesis and to enable the in vivo validation of drug discovery.