G protein-coupled receptors in vascular biology and diabetes

Description of projects available to graduate students:
G protein-coupled receptors (GPCRs) represent a major class of membrane-bound proteins that mediate a wide variety of biological functions, including sensitivity to light and odorants, endocrine and cardiovascular control, and neurotransmission. Because of their central role in many physiological processes, GPCRs represent one of the major targets for pharmacological intervention in a large number of pathologies.
The goal of our research program is the elucidation of the molecular mechanisms that determine activation, regulation and trafficking of GPCRs and their relevance to the (patho)physiology of peptide hormones.
These studies provide the opportunity to address key issues regarding the mode and specificity of actions of G protein-coupled receptors. Most importantly, these studies may provide the basis for the identification of novel therapeutic targets for the treatment of diabetes and vasculopathies.

Our efforts focus on two specific areas:
1.) The signaling, trafficking and regulation of the parathyroid hormone type 1 and type 2 receptors (PTH1R and PTH2R) and their function in vascular smooth muscle cells, with particular emphasis on their role in mitogenesis.
2.) Cellular regulation of the glucagon-like peptide 1 (GLP-1R) receptor and its role in regulating beta cell function, proliferation and survival.

To address these problems we use a multidisciplinary approach, from the synthesis of specialized peptides (containing fluorescent and photoreactive moieties), to the study of the cellular responses originating from these hormone-receptor complexes, to the determination of their activities in animal models (especially knockout mice).

Techniques graduate student will learn:
Cell and Molecular Biology Methods (tissue culture, mutagenesis, transfections,...)
Cell Signaling (Calcium, cAMP, MAPK,...)
Peptide Chemistry (design, synthesis, purification and analysis)
Vascular Biology (angioplasty, proliferation, migration)
Beta Cell Biology (insulin secretion, glucose metabolism, proliferation, survival)