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Molecular Signaling Section
Section Chief: Jürgen Wess, Ph.D.

About Our Research

G protein-coupled receptors (GPCRs) form a superfamily of cell surface receptors that serve as targets for a huge number of clinically useful drugs. The key focus of our research is to elucidate the physiological and pathophysiological roles of GPCRs and GPCR-associated proteins (with primary focus on beta-arrestin-1 and -2) in regulating the function of cell types that play central roles in maintaining proper blood glucose levels and body weight. During the past decade, we have generated and analyzed a large number of mutant mouse models that lack or over-express specific GPCRs (including designer GPCRs known as DREADDs) or beta-arrestin-1 or -2 in metabolically relevant cell types. We have analyzed these mice by a multi-pronged approach involving pharmacological, physiological, biochemical, electrophysiological, and molecular techniques. The ultimate goal of our wok is to identify novel targets for the treatment of several important diseases including metabolic disorders such as obesity and type 2 diabetes.

Research Images

Chart of Functional roles of beta-arrestins.
Functional roles of beta-arrestins
Chart of Novel designer GPCRs to probe GPCR function in vivo.
Novel designer GPCRs to probe GPCR function in vivo
Expression of designer GPCRs known as DREADDs in metabolically important cell types
Expression of designer GPCRs known as DREADDs in metabolically important cell types
Chart explaining Selective expression of a Gs-coupled designer receptor (Gs DREADD) in mouse AgRP neurons
Selective expression of a Gs-coupled designer receptor (Gs DREADD) in mouse AgRP neurons
Scheme summarizing how activation of Gs signaling in AgRP neurons promotes food intake in mice.
Scheme summarizing how activation of Gs signaling in AgRP neurons promotes food intake in mice
Generation of a mutant mouse strain expressing a Gi-coupled designer receptor (GiD= Gi DREADD) selectively in alpha cells of mouse pancreatic islets
Generation of a mutant mouse strain expressing a Gi-coupled designer receptor (GiD= Gi DREADD) selectively in alpha cells of mouse pancreatic islets
Images of selective expression of Gi-coupled designer receptor (Gi= Gi DREADD) in alpha cells of mouse panceatic islets
Selective expression of Gi-coupled designer receptor (Gi= Gi DREADD) in alpha cells of mouse panceatic islets
Scheme showing how activation of Gi signaling in alpha cells reduces both glucagon and insulin release in mouse pancreatic islets (GCG rec., glucagon receptor)
Scheme showing how activation of Gi signaling in alpha cells reduces both glucagon and insulin release in mouse pancreatic islets (GCG rec., glucagon receptor)
Scheme depicting that beta-arrestin-1 binding to Epac2A is required for the ability of sulphonylurea drugs to efficiently stimulate insulin release from mouse pancreatic beta-cells
Scheme depicting that beta-arrestin-1 binding to Epac2A is required for the ability of sulphonylurea drugs to efficiently stimulate insulin release from mouse pancreatic beta-cells
Last Reviewed February 2024