The Vilardaga Laboratory is directed at understanding molecular mechanisms of G protein-coupled receptor (GPCR) signaling and trafficking – two key processes in biological signaling in general and, more specifically, in pharmacology and drug research. Adrenergic and peptide receptors, which transmit signals, respectively for small neurotransmitters (such as noradrenaline and dopamine) and larger peptide hormones (vasopressin, parathyroid hormone, parathyroid hormone related peptide), are two well characterized distinct subtypes of GPCRs that serve as useful models for analyzing GPCR mechanisms. The objective of this line of research is to elucidate the general principles of signal transduction from the extracellular ligand binding event to intracellular signaling cascades, which are involved in systems as diverse as neurotransmitter and hormonal signaling.
Optical approaches (eg. FRET, TIRF microscopy) are used to monitor the activation/deactivation steps along the signaling cascades of GPCRs in live cells. This approach revealed fundamental mechanisms of GPCRs signaling and trafficking in live cells for neurotransmitter and peptide hormones such as the PTH, which were published in 2003-2007 in Nature Biotech, Nature Methods, Nature Chemical Biology, the Journal of Biological Chemistry and PNAS.
Recently Vilardaga laboratory also discovered the new concept that persistent cAMP production mediated by parathyroid hormone receptor endocytosis may mediate potent catabolic signaling actions via PTH (PNAS 2008, Nature Chem Biol 2009). This prolonged cAMP production from intracellular compartments further indicate that the traditional concept that cAMP production triggered by GPCRs originates exclusively at the cell membrane must be revised. The main focus of my current research aims at determining the origin of the prolonged signaling by GPCRs and its termination. These events and consequent signaling patterns are quite novel and important for cellular signaling.