Our laboratory investigates the cellular and molecular mechanisms by which the host antiviral response is influenced by both commensal and pathogen interactions. Research focuses on using a combination of molecular and cell biologic approaches, in concert with in vitro and animal modeling systems, to establish an understanding of host-commensal-pathogen interactions. Central to our studies is our ability to utilize host genetic strategies to perturb these interactions in order to define precise molecular events in pathogenesis and then apply this knowledge to derive novel insights for treatment strategies.
Our early work demonstrated that genetic and environmental enhancement of type I interferon signaling protects from Influenza pathogenesis. Specifically, this work uncovered the role of microbial metabolism in antiviral immunity and has important clinical ramifications. Given the findings that the microbiota and microbiota-derived metabolites are critical regulators of respiratory viral infection, understanding the impact of the microbiota on the host immune response and tissue reparative programs is an important ongoing focus of the laboratory.
Our group has also investigated the immune response to SARS-CoV-2 when the pandemic arose. One translational study used single-cell RNA sequencing to elucidate peripheral blood cell type specific transcriptional signatures that associate with and predict survival in critical COVID-19 ARDS. Subsequent in vitro and small scale animal modeling work demonstrated that the SARS-CoV-2 surface proteins spike and envelope alone activate the interferon signaling pathway in both immune and epithelial cells and induced peribronchial inflammation and pulmonary vasculitis.
Current research projects include:
- Effect of age on antiviral immunity
- Impact of viral latency on subsequent pathogenic infections
- Role of the microbiota in modulation of the host immune response