G protein coupled receptors (GPCRs) are a class of ubiquitous cell-surface receptors that regulate many physiological functions such as cardiovascular, neuronal, and immune functions. On the cell surface, GPCRs act as extracellular biosensors that are triggered by a variety of stimuli including photons, ions, small molecules, peptides etc. Upon stimulation by extracellular ligands, GPCRs communicate with the interior of the cell by transmitting a signal that leads to an appropriate cellular response. Due to their location on the cell surface, ability to bind smaller molecules, and involvement in most aspects of physiology, GPCRs have become popular drug targets with 30%-50% of all prescribed drugs affecting them.
Over the last 10 years, it has been appreciated that some GPCRs not only initiate signaling from the cell surface, but also while they are internalized into endosomes. This discovery was initially surprising and difficult to understand because receptor endocytosis classically has been linked to termination of GPCR signaling. However, during his postdoctoral training in the Nobel Prize-winning Lefkowitz Laboratory at Duke University, Dr. Thomsen studied and delineated mechanisms involved in endosomal GPCR signaling and demonstrated that certain GPCRs form mega-complexes, which allows them to continue to signal while being internalized into endosomes. These studies were published in the scientific journals Cell, PNAS, and Nature Structural & Molecular Biology.
The early mechanistic discoveries related to endosomal GPCR signaling form the basis of the research activities in the Thomsen Lab at New York University. The major objective of the laboratory is to expand upon these findings and investigate the physiological/pathophysiological functions of this newly appreciated signaling mechanism. The laboratory is currently focused on chemokine receptors and how signaling from endosomes may control specific cell physiological processes such as cell differentiation and migration in immune and cancer cells.
- For additional information, please visit: thomsen-lab.com
The Thomsen Lab studies GPCRs from multiple perspectives, all the way from a near-atomic resolution to entire cells, using a variety of approaches.
- Biophysical (BRET, FRET, TR-FRET) approaches to study GPCR signaling and trafficking in model cells and primary tissue.
- Imaging (confocal, super-resolution microscopy) approaches to evaluate GPCR trafficking in model cells and primary tissue.
- Proteomic approaches to identify components of GPCR complexes and trafficking proteins during GPCR activation.
- Biochemical in vitro approaches to test mechanistic hypotheses using purified and reconstituted components.
- Cryo-electron microscopy to obtain at high-resolution snap shots of GPCR complexes in purified systems or in cells.
- Physiological and genomic approaches to study biological responses to GPCR signaling from different intracellular compartments.