How do spatial and temporal signals control cell polarization, movement, and proliferation?
Section Styles gold-border
We ask how receptor signals at the plasma membrane are spatially and temporally controlled to regulate cell migration and proliferation.
In recent work, we identified critical roles of the actin cortex and ER-PM contact sites in polarizing and sensitizing receptor signaling, which in turn controls whether and how cells migrate, proliferate, and differentiate.
Our Next Research Directions
We are developing photolithography methods and new classes of fluorescent reporters to study the signaling processes controlling cell polarization and migration by focusing on the spatial and temporal control of receptor signaling at the plasma membrane.
Open projects focus on developing approaches to spatially map differences in local receptor and signaling activities, understanding the consequence of rapid small molecule perturbations, mechanisms of drug action, performing genetic screens, and confocal and super-resolution fluorescence microscopy. The overall goal is to understand how the actin cortex and ER-PM contact sites regulate receptor signaling to control cell migration and proliferation.
Relevant Publications
➢ Structural mechanism for bidirectional actin cross-linking by T-plastin. PNAS 2022
➢ Enhanced substrate stress relaxation promotes filopodia-mediated cell migration. Nat Materials 2022
➢ Membrane proximal F-actin restricts local membrane protrusions and directs cell migration. Science 2020
➢ T-Plastin reinforces membrane protrusions to bridge matrix gaps during cell migration. Nat Commun 2020
➢ Efficient Front-Rear Coupling in Neutrophil Chemotaxis by Dynamic Myosin II Localization. Dev Cell 2020
➢ PLEKHG3 enhances polarized cell migration by activating actin filaments at the cell front. PNAS 2016
➢ Engulfed cadherin fingers are polarized junctional structures between collectively migrating endothelial cells. Nat Cell Biol 2016
➢ Waves of actin and microtubule polymerization drive microtubule-based transport and neurite growth before single axon formation. Elife 2016
➢ Locally excitable Cdc42 signals steer cells during chemotaxis. Nat Cell Biol 2016
➢ A polarized Ca2+, diacylglycerol and STIM1 signalling system regulates directed cell migration. Nat Cell Biol 2014
➢ A localized Wnt signal orients asymmetric stem cell division in vitro. Science 2013
➢ Cooperative activation of PI3K by Ras and Rho family small GTPases. Mol Cell 2012