Philip Kranzusch

Research Description

Our lab studies how cells sense and defend from pathogen infection. We discovered that the core components of human innate immunity are surprisingly ancient, evolving billions of years ago in bacteria as pathways that defend against bacteriophage replication. Building on the direct link between animal immunity and bacterial anti-phage defense, the goals of our current research are to discover new mechanisms of immune signaling and to define shared rules that govern host-pathogen interactions across all kingdoms of life.

A major mechanism of immune activation conserved between human cells and bacteria are enzymes that produce nucleotide second messenger signals to control viral infection. We discovered that the human protein cGAS (cyclic GMP–AMP synthase) critical for antiviral and antitumor immunity is part of a broad family of signaling enzymes that includes anti-phage defense proteins in bacteria named CD-NTases (cGAS/DncV-like Nucleotidyltransferases) and diverse pattern recognition receptors in animal cells named cGLRs (cGAS-like receptors). Our results define thousands of uncharacterized immune receptors, demonstrating fundamental gaps in our understanding of how bacteria and human cells defend against viral infection.

Ongoing research areas in our lab include identifying novel classes of nucleotide signals that control immune activation, determining the structural basis of how receptors sense pathogen replication and induce downstream signaling, and explaining evolution of the viral machinery responsible for evading host defense.