The overall goal of my lab is to understand the roles of compartmentalized, organelle-based signaling and membrane trafficking as two key steps which allow cells to respond to external cues. As the plasma membrane provides a barrier to many hormones and biogenic amines, these external cues act by engaging cell surface receptors. A long held tenet of molecular pharmacology is that for cell surface receptors, signal transduction is plasma membrane delimited and that removing the receptors from the plasma membrane is a mechanism for shutting down signaling. We have recently shown that G protein coupled receptors (GPCRs), the largest and most versatile family of plasma membrane receptors, activate G protein-mediated signaling pathways at previously unrecognized internal compartments such as endosomes and the Golgi apparatus. As such, subcellular organization of GPCR-mediated signaling represents a new frontier of spatially organized cellular signaling with broad implications for physiological and pathological processes. We use novel biosensors, sophisticated microscopy, cell biology, pharmacology, and ultimately physiology to study the compartmentalized signaling.
On-going Research Projects:
1) Cell biological consequences and dynamics of receptor signaling from the internal membranes.
2) Understanding the molecular mechanisms of receptor activation and inactivation at the internal membrane compartments using proteomics approaches.
3) Using mouse models to study the role of monoamine transporters in regulating GPCR signaling from internal membrane compartments.
4) Developing novel tools to study the roles of GPCR compartmentalized signaling in regulating heart functions in intact zebrafish hearts.
Imaging zebrafish heart using a cardiac endothelial cell reporter line (flk1:GFP)
