Dr. Sen's research interests are in two areas: mechanism of regulation and functions of viral stress-inducible genes (VSIG) and tissue specific functions of angiotensin-converting enzyme (ACE). Transcription of a group of mammalian genes is strongly induced by a variety of stimuli related to virus infection such as double-stranded (ds) RNA, interferons and viral proteins. He is identifying these genes (VSIG) and delineating the distinct signaling pathways used for inducing these genes. Current efforts are concentrated on TLR3 and RIG-I signaling pathways and he has recently discovered two new branches of these pathways. The VSIG P56 proteins inhibit protein synthesis by interacting with eIF-3. P56 also inhibits human papilloma virus DNA replication by binding to the viral E1 protein. The IFN-induced protein kinase, PKR and its activator, PACT, are two dsRNA-binding proteins. He discovered PACT and determined how it activates PKR. Dr. Sen has generated PACT-knockout mice which have specific developmental defects of the anterior pituitary. In addition to its pivotal role in blood pressure regulation, angiotensin-converting enzymes have essential roles in renal, immunological and male reproductive functions. Using tissue-specific transgene expression in Ace-/- mice, we have shown that the germinal isozyme of ACE in sperm is sufficient for maintaining male fertility and regulation of blood pressure and maintenance of normal kidney functions are two separable properties of the somatic isozyme.