Regulation of cell fate determination by the Hippo signaling pathway
The main interest of my lab is understanding how the Hippo signaling pathway controls cell fate decisions in response to a diverse array of stimuli, in particular mechanical forces. The Hippo pathway is a protein kinase-mediated network that regulates cell proliferation, contact inhibition, apoptosis, stem cell maintenance, differentiation, and tissue regeneration. Misregulation of this pathway has deleterious effects on cells and organisms and can lead to cancer. Hippo signaling controls the nuclear localization of the transcriptional co-activator YAP in response to various stimuli that affect the mechanical environment of the cell such as cell crowding, substrate stiffness, tension, and cell detachment. The ability to sense these types of changes to the mechanical environment is crucial for regulation of stem cell niches, wound healing, contact inhibition of growth, and tumor suppression. My lab uses cell and molecular biology, genetics, and biochemical approaches to determine how cells sense changes in the mechanical environment and regulate cell fate through control of Hippo signaling.
Regulation of Hippo signaling by mechanical stimuli.
The Hippo pathway is known to monitor the mechanical environment both indirectly through the effects of various stimuli on the actin cytoskeleton, and more directly by sensing tension across tissues. My lab's focus has been on determining how F-actin levels and tension at cell-cell junctions are sensed, and how these signals are transduced to control Hippo signaling. We identified the angiomotin proteins as Hippo pathway sensors for F-actin levels and are currently studying how they control Hippo signaling. Our studies have also uncovered new Hippo pathway regulators at cell-cell junctions that may directly sense tension across tissues. Current research in the lab is focusing on understanding the molecular mechanisms underlying F-actin and tension sensing, and how signals from separate sensors are integrated to generate cellular responses to mechanical stimuli.