We are motivated by the widespread understanding that a productive immune response always exerts some degree of collateral damage to healthy tissue. However, our past work taught us that the amount of collateral damage tolerated by a tissue is quantitatively regulated by innate immune cells based on the threat of infection. In other words, a tunable tradeoff exists between host defense and tissue damage, and our goal is to identify the cellular and tissue-level properties that regulate this tradeoff. To achieve this goal, our work uses systems and quantitative approaches to explore how the spatial organization of immune cells in tissue affects their phenotypic and functional plasticity during infection and homeostasis. On a more fine-grained level, the work in our lab can currently be divided into three major wings:

1. Investigate how phenotypic and functional heterogeneity in regulatory T cells relates to their physical proximity to effector T cells. We combine approaches from synthetic biology, whole-organ light sheet imaging, and ex vivo 3D cell culture to examine how the physical proximity of effector T cells and Tregs transiently molds Treg phenotype and function during the early immune response.

2. Examine how microbial traffic primes resident macrophages for responses to infection. We are taking a systems biology approach to compare and contrast the threshold for inflammatory responses in resident macrophages isolated from immune privileged sites and sites of high microbial traffic.

3. Identify the cellular factors that predispose virus-infected cells towards either immunologically silent or inflammatory forms of cell death. We are combining live cell imaging, machine learning, and single cell RNA sequencing to identify the transcriptional signatures that predispose virus-infected cells towards different death fates.