Direction 3. Regulatory mechanisms of macrophage states
We are currently focused on the critical role of macrophages in preventing inappropriate activation of inflammatory processes that would otherwise damage healthy tissues.
Central to the power and innovation of our approach is the use of forward genetics to discover genes when disrupted cause inappropriate spontaneous activation of macrophages in the absence of any overt challenge in addition to generation of endogenous knock-in reporters that confer different activation states of macrophages. Unlike the conventional Tol2 transposon mediated transgenes, these reporters are precisely controlled to integrate at a single site enabling reliable quantification and comparison from individual to individual.
Bulk and single-cell transcriptome analyses combined with advanced in vivo imaging of single cell tracking allow us to investigate the dynamic range and flexibility of states that macrophages adopt in vivo in different physiological contexts.