Research

Recent advances in our understanding of tuberculosis infection demonstrate that infection within a given individual is highly heterogeneous; however, the determinants that drive lesions towards complete bacterial sterilization remain poorly understood. We are interested in developing new tools to dissect the complex dynamics of bacterial infection at a variety of scales ranging from single cells to infected hosts sitting in both “reference frames” by taking both an immunologist’s and a microbiologist’s perspective. Combining new technologies with classical approaches, we are focused ultimately on the goal to manipulate the immune system to improve bacterial control.

Our research revolves around two motivating questions –

1. What macrophage processes contribute to effective bacterial killing and what are the bacterial evasion mechanisms to resist such stress?


2. How can manipulate macrophage plasticity and program macrophage function in homeostasis and disease?

To this end, we are pursuing several projects aimed at both answering these question directly and developing new tools to further our understanding of these complex bacterium:host interactions.

Tools

Bacterium:host protein:protein interactions using genetically-encoded methods of extracting complexes

Sydney Solomon

Novel single-cell algorithms to analyze datasets across diverse methods and samples

Brian Hie

Multiplexed, pooled infections for interrogating strain-based heterogeneity among host cell populations

Josh Peters

Biology

Macrophage plasticity and commitment in response to differentiation cues and cytokines

Chris Itoh, Brian Hie, Josh Peters

Host-modulating bacterial factors and impact on host heterogeneity

Josh Peters

Host-directed agents to manipulate macrophage state in favor of bacterial control