Viral antagonism as a lens on cellular regulation
The lab combines biochemistry and structural biology with bioinformatics to determine how viruses antagonize nucleotide-based signaling: Using viral immune antagonists as a lens to study the diversification of immunity at the molecular level and the lasting consequences of this dysregulation beyond acute infection.
What
We study how viruses disrupt immune signaling, and how host immunity responds to these antagonistic mechanisms.
Why
Understanding these interactions will inform therapeutic design—in the context of infectious and non-infectious disease—and reveal the consequences of immune dysregulation beyond acute infection.
How
We combine biochemistry, structural biology, and bioinformatics to uncover the molecular mechanisms underlying virus-host conflict.
RNA editing is an essential process in which endogenous metazoan enzymes recode RNA. This process has been co-opted for the correction of mutations underlying genetic disease (Doherty et al. JACS, 2021; Doherty et al. NAR, 2022). However, this process is also critical for maintaining homeostasis, and plays a dual role in immunity and broader transcript regulation, including modulating neuronal function. In immunity, RNA editing can prevent endogenous RNA from being recognized as a pathogen-associated molecular pattern by innate immune receprs–a mechanism that is often co-opted by viruses.
Our lab is interested in the interactions between viruses and host RNA editing machinery. Understanding mechanisms that drive dysregulation of RNA editing,may provide insight into therapeutic strategies for diseases associated with aberrant RNA editing, including Aicardi-Goutières syndrome, cancer, and epilepsy.
Immune systems across the tree of life use nucleotides as building blocks to create cyclic oligonucleotide second messengers that signal infection. Our lab is interested in how these cyclic oligonucleotides are involved in diverse immune responses (Doherty & Adler et al., Nature, 2025). Similarly, we are interested in conserved mechanisms that viruses use to counteract these pathways (Doherty & Nomburg et al. Cell Host & Microbe, 2025).
Beyond defining a new mechanism of innate immune sensing, oligonucleotide signaling is a major axis of human health, in which these molecules influence not only antiviral immunity but also chronic inflammation, autoimmunity, cancer, and neurodegenerative disease.
