What we do

Understanding immune system biology through the study of viral and parasitic infections.

 
 
Cover of issue featuring herpesvirus-helminth co-infection work.

Cover of issue featuring herpesvirus-helminth co-infection work.

Using co-infections to investigate herpesvirus reactivation

We are all infected with multiple viruses, bacteria, fungi, and parasites. The immune response to single pathogen infections has been extensively studied, but little is known about the immune response to coinfections. Specifically, we do not understand the impact of bystander infections on viral pathogenesis. My lab is pioneering the use of novel mouse models of multiple infections to investigate the complex interactions that occur during coinfection. We demonstrated through our mouse models that infections with intestinal parasites reactivate latent gammaherpesvirus infections (Reese, Science 2014; Wang, J Virol 2021). We recently discovered that when we alter the order of parasite and virus coinfection, we observe mechanistically distinct herpesvirus reactivation (Zarek, PLOS Path, 2023). Our work is some of the first to detail a mechanism for coinfection induced herpesvirus reactivation and we are one of the only labs investigating coinfection effects of DNA virus infection.

 

Model for NS3 induced cell death during MNV infection. Created with BioRender

Using Viruses to Discover Novel Cell Biology

In addition to our coinfection studies, we study viruses to uncover novel mechanisms of antiviral immunity. We aim to determine the mechanisms used by viruses to manipulate the cell, with the goal of finding novel ways to enhance antiviral immunity. We use diverse viruses, including herpesviruses and noroviruses to probe redox regulation of signaling pathways and programmed cell death during infection. Using these systems, we discovered that increased reactive oxygen species production during herpesvirus infection inhibits interferon production through redox regulation of the signaling adapter STING (Tao, eLife, 2020). We also discovered that norovirus NS3 induces mitochondrial disruption, which promotes a novel form of cell death that is required for norovirus replication and egress (Wang, Nature 2023). We are currently investigating the mechanisms that underly NS3 targeting of mitochondria, with a particular emphasis on cardiolipin externalization. This work has the potential to uncover shared mechanisms that viruses use to induce cell death and promote viral egress.

 
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Investigating vaccine responses in microbially experienced mice

The state of the immune system and its ability to respond to challenge is a function of many variables, which include genetics, age, chronic disease, gut microbiome, and stress. Recent work suggests that a significant proportion of the variation in human immune response is driven by non-heritable or environmental influences.

Laboratory mice are usually housed in specific pathogen free animal facilities and have minimal exposure to pathogens. Our work (Reese, CHM, 2015; Chlebicz, Ann Rev Virol, 2026) and work by others indicate that mice with high microbial exposure have immune responses that more closely mimic human immune responses. We are using a sequential infection model to make ‘dirty mice’ to investigate the mechanisms that drive differences in vaccine responses between mice with microbial experience and SPF mice. This work aims to create mouse models more faithfully mimic human immune responses and define mechanisms by which microbial exposure matures the immune system.