Welcome to the Hague Lab Home Page
Our laboratory studies the molecular pharmacology of the G protein-coupled receptors (GPCRs). We are located at the University of Washington School of Medicine in D-430/431 of the Health Sciences Building.
The goal of our research is to understand the molecular mechanisms of drug action at G protein-coupled receptors (GPCRs). We are currently focused on deciphering how GPCRs are organized as macromolecular protein complexes in cell membranes. We recently revealed the alpha1D-adrenergic receptor, a key regulator of cardiovascular, nervous system, and urinary function, associates with the multiple PDZ-domain containing proteins in human cells, and that these interactions are unique amongst human GPCRs containing Type I PDZ binding motifs. Current research in the Hague lab aims to:
1) Understand the structural features of the alpha1D-adrenergic receptor macromolecular complex. We recently discovered this clinically relevant GPCR forms a homodimeric, modular multi PDZ protein complex (Camp et al, Cell Discovery, 2015). More specifically, it associates with PDZ-proteins Scribble and Syntrophins in all human cell lines examined thus far. However, we have yet to determine the architecture of this complex.
2) Identify novel GPCR macromolecular complexes using molecular/cellular biology and mass spectrometry/proteomics.
3) Determine how components of GPCRs macromolecular complexes impact the actions of clinically relevant drugs.
Understanding how GPCRs are organized as macromolecular complexes in human cells will identify novel drug target interfaces that can be exploited to develop novel small molecule therapeutics to treat human diseases.
1) Understand the structural features of the alpha1D-adrenergic receptor macromolecular complex. We recently discovered this clinically relevant GPCR forms a homodimeric, modular multi PDZ protein complex (Camp et al, Cell Discovery, 2015). More specifically, it associates with PDZ-proteins Scribble and Syntrophins in all human cell lines examined thus far. However, we have yet to determine the architecture of this complex.
2) Identify novel GPCR macromolecular complexes using molecular/cellular biology and mass spectrometry/proteomics.
3) Determine how components of GPCRs macromolecular complexes impact the actions of clinically relevant drugs.
Understanding how GPCRs are organized as macromolecular complexes in human cells will identify novel drug target interfaces that can be exploited to develop novel small molecule therapeutics to treat human diseases.