Research interests

Human norovirus is a leading cause of acute gastroenteritis and manifests as profuse diarrhea and vomiting. While norovirus outbreaks are commonly linked to cruise ships, the disease burden is greatest in young children, which represent the majority of the up to 200,000 deaths per year. There are currently no medications or vaccines to treat or prevent human norovirus infection. This is, in part, a result of our limited understanding about how norovirus establishes infection and causes disease. For instance, it is unclear how norovirus enters cells, what cells the virus can infect, how infection causes symptoms,  and how the virus can establishes persistent infection in some people. We use mouse and organoid models to study norovirus pathogenesis in vitro and in vivo with the long term goal of developing effective vaccines and anti-virals.

SARS-CoV-2 is the causative agent of COVID-19.  To identify novel drug targets and to decipher mechanisms of host-virus interactions, we use genome-wide CRISPR screens, organic culture, and mouse and hamster models to study coronavirus pathogenesis and immunity. We have uncovered novel epigenetic mechanisms which determine coronavirus susceptibility and receptor expression. Current work in the lab is focused on viral and host mechanisms of immune escape and virus transmission. 

Thousands of viruses with human infection potential circulate in wild animals particularly bats, representing a future pandemic threat.  A major knowledge gap exists in our ability to predict which bat viruses can infect human cells, transmit, and cause disease. Our goals are to discover the host and viral determinants of pathogenesis of pre-emergent viruses to improve surveillance, risk stratification, and aid development of countermeasures to mitigate future pandemics. We are also focused on novel properties of the bat immune system which enable them to be reservoirs for such diverse pathogenic viruses.

Tuft cells are named after their long tuft of microvilli that protrudes into the intestinal lumen. They are rare chemosensory cells that sense and respond to small molecules and microorganisms within the intestines.  Most notably, they secrete the cytokine IL-25 in response to worm infection which initiates a type II immune response to combat worm infection. Tuft cell link the enteric nervous system, the immune system, and intestinal epithelium as they require neuronal innervation for survival, and are critical to effectively clear intestinal worms and parasites. However, much about their function, including their role in viral infection and immunity, remains a mystery.