Research interests

Human norovirus causes profuse diarrhea and vomiting. While norovirus outbreaks are commonly linked to cruise ships, the disease burden is greatest in young children in the developing world, which represent the majority of the 200,000 deaths per year due to this poorly understood virus. 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 unknown what types of cells norovirus infects, how it infects a given cell, how it spreads between cells, and how it establishes persistent infection in some people. We use mouse models and stem-cell derived intestinal enteroids to study norovirus pathogenesis in vitro and in vivo.

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 new coronaviruses circulate in wild animals particularly bats, representing a future pandemic threat.  While many of these bat coronaviruses have been sequenced, few have been cultured and phenotypically characterized. 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 novel bat coronaviruses to improve surveillance and aid the 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.