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.
|Genuth, Miriam A; Allen, Christopher D C; Mikawa, Takashi et al. (2018) Chick cranial neural crest cells use progressive polarity refinement, not contact inhibition of locomotion, to guide their migration. Dev Biol :|
|Liu, Zairan; Woo, Stephanie; Weiner, Orion D (2018) Nodal signaling has dual roles in fate specification and directed migration during germ layer segregation in zebrafish. Development 145:|
|Saha, Suvrajit; Nagy, Tamas L; Weiner, Orion D (2018) Joining forces: crosstalk between biochemical signalling and physical forces orchestrates cellular polarity and dynamics. Philos Trans R Soc Lond B Biol Sci 373:|
|Reade, Anna; Motta-Mena, Laura B; Gardner, Kevin H et al. (2017) TAEL: a zebrafish-optimized optogenetic gene expression system with fine spatial and temporal control. Development 144:345-355|
|Graziano, Brian R; Gong, Delquin; Anderson, Karen E et al. (2017) A module for Rac temporal signal integration revealed with optogenetics. J Cell Biol 216:2515-2531|
|Yang, Yang; Xiong, Ding; Pipathsouk, Anne et al. (2017) Clathrin Assembly Defines the Onset and Geometry of Cortical Patterning. Dev Cell 43:507-521.e4|
|Buckley, Clare E; Moore, Rachel E; Reade, Anna et al. (2016) Reversible Optogenetic Control of Subcellular Protein Localization in a Live Vertebrate Embryo. Dev Cell 36:117-126|
|Hoeller, Oliver; Toettcher, Jared E; Cai, Huaqing et al. (2016) G? Regulates Coupling between Actin Oscillators for Cell Polarity and Directional Migration. PLoS Biol 14:e1002381|
|Liu, Zairan; Weiner, Orion D (2016) Positioning the cleavage furrow: All you need is Rho. J Cell Biol 213:605-7|
|Diz-Muñoz, Alba; Thurley, Kevin; Chintamen, Sana et al. (2016) Membrane Tension Acts Through PLD2 and mTORC2 to Limit Actin Network Assembly During Neutrophil Migration. PLoS Biol 14:e1002474|
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