My lab investigates the dynamics of chemosensory mechanisms involving novel nutrient-sensing G protein-coupled receptors (GPCRs), such as sweet taste receptors (STRs). Beyond the tongue, STRs are expressed in the intestine, pancreas, adipose tissue, and the brain where they likely function as nutrient sensors to coordinate adaptive responses to nutrient availability (ingested or circulating).

Our laboratory has pioneered studies on the role of sweet taste receptors (STRs) on pancreatic beta-cells, while ongoing studies have unveiled novel roles of STRs in other relevant tissues to metabolism, such as the gut and the skeletal muscle. The long-term goal of these projects is to understand and extend mechanistic observations made in mouse models of nutrient-sensing receptor biology to human physiology and metabolic disease.

Project A: “Nutrient interactions and the chemosensory role of STRs in the gut”

Using mice with intestine-specific deletion of the t1r2 gene of STRs we will:

1. Elucidate the undefined role of intestinal STRs in local gut physiology and in the regulation of glucose absorption and metabolism 
2. Determine the contribution of intestinal T1R2 chemosensor in the regulation of gut microbiota and assess its significance for the metabolic control of the host.
3. Assess the adaptive effects of sugar-induced downregulation of intestinal STRs on postprandial glucose homeostasis.
4. Delineate the contribution of intestinal STRs in the development of metabolic derangements linked to overconsumption of sugars and NCASs.

Project B: “T1R2 chemoreceptor signaling in skeletal muscle”

Using mice with skeletal muscle-specific deletion of the t1r2 gene of STRs we will:

1. Delineate the role of the T1R2 chemoreceptor signaling in the regulation of substrate flux and metabolism in mouse and human cultured myotubes
2. Investigate the effects of muscle-specific ablation of the T1R2 chemoreceptor on energy regulation and metabolic disease progression in vivo.

Project C (Clinical): “Interactions of human gut microbiota with intestinal STRs”

This pilot and feasibility study was designed to address whether:

1. Short-term consumption of NCASs (saccharin) can induce glucose intolerance and uniform changes in gut microbiota
2. Short-term pharmacological inhibition of intestinal STRs can a) prevent NCAS-induced glucose intolerance, or b) independently alter metabolic responses to an OGTT
3. The effects of NCAS consumption on glucose homeostasis and gut microbiota are dependent on common taste receptor gene polymorphisms.