My lab is broadly interested in how signaling networks generate complex cell behaviors such as polarity and motility. Understanding how these complex networks function requires tools to isolate and interrogate individual steps in the signaling cascade. We have invested significant effort developing novel optogenetic tools that enable us to activate or inhibit intracellular signals in a manner that is rapid, reversible, titratable, and can be manipulated in space and time. Initially we developed these tools to understand the regulation of polarity and motility during neutrophil chemotaxis. We are particularly interested in the molecular basis of the sensory adaptation that accounts for the remarkable dynamic range of chemotaxis and how cells convert small asymmetries in external agonist to large asymmetries in actin assembly for efficient directional movement. More recently, we have expanded our optogenetic toolkit to probe other signaling networks, such as how T cells discriminate between chemically similar ligands and commit to all-or-none activation. We continue to develop the technology to bring a wider range of signals and systems under optogenetic control, such as our analysis of pattern formation during zebrafish development.
Our work focuses on how signaling networks generate complex cellular behaviors such as neutrophil polarity and motility and all-or-none switches, such as T cell activation. The ability t control cell migration would be a valuable tool for combating atherosclerosis, inflammation, metastasis, and other pathological processes that occur upon the disruption of cellular guidance mechanisms. Our work on the mechanism of T cell activation will directly impact our understanding of autoimmune disease, vaccine development, and the initiation of an immune response.
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