
Research Summary:
Proper movement in response to cues from the outside world is as important for single cells as it is for drivers on a busy highway. If cues are misinterpreted or the movement goes awry, terrible accidents ensue, the delicate wiring of the nervous system fails, single-celled organisms can`t hunt or mate, the immune system ceases to function properly, and cancer cells spread from one part of the body to another. How do single cells, without the benefit of a brain, interpret the subtle micro-world of attractants and repellents to decide where to go? Our research focuses on dissecting the inner workings of the cellular "compass" used to guide cells on their journey. Because the core of the compass has been conserved over more than a billion years of evolution, we have been able to combine discoveries from yeast to humans to glimpse some rough outlines of the underlying machinery. However, many of the important connections are still missing. Our research focuses on identifying these key missing components and how they are wired together to process information with the hope that we can eventually make cells move when (and where) we want them to and stop them when we don't.
Publications
YAP charge patterning mediates signal integration through transcriptional co-condensates.
WAVE complex forms linear arrays at negative membrane curvature to instruct lamellipodia formation.
Long range mutual activation establishes Rho and Rac polarity during cell migration.
Investigating local negative feedback of Rac activity by mathematical models and cell motility simulations.
Emerging roles of transcriptional condensates as temporal signal integrators.
ER-GUARD: an evolutionarily conserved antioxidant defense system at ER membranes.
YAP charge patterning mediates signal integration through transcriptional co-condensates.
Follow the flow: Actin and membrane act as an integrated system to globally coordinate cell shape and movement.
The WAVE complex forms linear arrays at negative membrane curvature to instruct lamellipodia formation.
Self-extinguishing relay waves enable homeostatic control of human neutrophil swarming.
Rationally seeded computational protein design of ɑ-helical barrels.
Plasma membrane abundance dictates phagocytic capacity and functional cross-talk in myeloid cells.
Neutrophils actively swell to potentiate rapid migration.
Early-life stress triggers long-lasting organismal resilience and longevity via tetraspanin.
Early-life stress triggers long-lasting organismal resilience and longevity via tetraspanin.
Optogenetic control of YAP reveals a dynamic communication code for stem cell fate and proliferation.
Plasma membrane abundance dictates phagocytic capacity and functional crosstalk in myeloid cells.
Molecular mechanism of GPCR spatial organization at the plasma membrane.
Self-extinguishing relay waves enable homeostatic control of human neutrophil swarming.
Mechanosensitive mTORC2 independently coordinates leading and trailing edge polarity programs during neutrophil migration.
Adhesion-independent topography-based leukocyte migration.
WASP integrates substrate topology and cell polarity to guide neutrophil migration.
The WAVE complex associates with sites of saddle membrane curvature.
Multiple sources of signal amplification within the B-cell Ras/MAPK pathway.
Light-based tuning of ligand half-life supports kinetic proofreading model of T cell signaling.
Nodal signaling has dual roles in fate specification and directed migration during germ layer segregation in zebrafish.
In pursuit of the mechanics that shape cell surfaces.
Joining forces: crosstalk between biochemical signalling and physical forces orchestrates cellular polarity and dynamics.
Chick cranial neural crest cells use progressive polarity refinement, not contact inhibition of locomotion, to guide their migration.
Clathrin Assembly Defines the Onset and Geometry of Cortical Patterning.
A module for Rac temporal signal integration revealed with optogenetics.
TAEL: a zebrafish-optimized optogenetic gene expression system with fine spatial and temporal control.
Positioning the cleavage furrow: All you need is Rho.
Membrane Tension Acts Through PLD2 and mTORC2 to Limit Actin Network Assembly During Neutrophil Migration.
Gβ Regulates Coupling between Actin Oscillators for Cell Polarity and Directional Migration.
Reversible Optogenetic Control of Subcellular Protein Localization in a Live Vertebrate Embryo.
Cell Migration: Recoiling from an Embrace.
Probing Yeast Polarity with Acute, Reversible, Optogenetic Inhibition of Protein Function.
Myosin light chain kinase regulates cell polarization independently of membrane tension or Rho kinase.
Homer3 regulates the establishment of neutrophil polarity.
Illuminating cell signalling with optogenetic tools.
Self-organization of protrusions and polarity during eukaryotic chemotaxis.
Response to Bell et al.
Synthetic control of mammalian-cell motility by engineering chemotaxis to an orthogonal bioinert chemical signal.
How to understand and outwit adaptation.
How should we be selecting our graduate students?
An optogenetic gene expression system with rapid activation and deactivation kinetics.
Using optogenetics to interrogate the dynamic control of signal transmission by the Ras/Erk module.
Actin dynamics rapidly reset chemoattractant receptor sensitivity following adaptation in neutrophils.
The symphony of cell movement: how cells orchestrate diverse signals and forces to control migration.
Two distinct functions for PI3-kinases in macropinocytosis.
A light-inducible organelle-targeting system for dynamically activating and inactivating signaling in budding yeast.
Identifying network motifs that buffer front-to-back signaling in polarized neutrophils.
Use the force: membrane tension as an organizer of cell shape and motility.
Nodal signaling regulates endodermal cell motility and actin dynamics via Rac1 and Prex1.
Diffusion, capture and recycling of SCAR/WAVE and Arp2/3 complexes observed in cells by single-molecule imaging.
A pharmacological cocktail for arresting actin dynamics in living cells.
Light control of plasma membrane recruitment using the Phy-PIF system.
The promise of optogenetics in cell biology: interrogating molecular circuits in space and time.
Manipulation of neutrophil-like HL-60 cells for the study of directed cell migration.
Cell stimulation with optically manipulated microsources.
Neutrophils establish rapid and robust WAVE complex polarity in an actin-dependent fashion.
Chemotaxis in neutrophil-like HL-60 cells.
Rac1 links leading edge and uropod events through Rho and myosin activation during chemotaxis.
A chemical compass.
A PtdInsP(3)- and Rho GTPase-mediated positive feedback loop regulates neutrophil polarity.
Lipid products of PI(3)Ks maintain persistent cell polarity and directed motility in neutrophils.
Rac activation: P-Rex1 - a convergence point for PIP(3) and Gbetagamma?
Regulation of cell polarity during eukaryotic chemotaxis: the chemotactic compass.
PIP3, PIP2, and cell movement--similar messages, different meanings?
Leukocytes navigate by compass: roles of PI3Kgamma and its lipid products.
Polarization of chemoattractant receptor signaling during neutrophil chemotaxis.
Enteropathogenic E. coli acts through WASP and Arp2/3 complex to form actin pedestals.
Spatial control of actin polymerization during neutrophil chemotaxis.
Dynamics of a chemoattractant receptor in living neutrophils during chemotaxis.
Medium weight neurofilament mRNA in goldfish Mauthner axoplasm.
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