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Inactive Ras protein (left) is activated by a GEF protein opening the binding site allowing GDP to exit. Afterwards GTP can bind to RAS turning it into the active form (right). Ras proteins are involved in transmitting signals within cells turning on genes involved in cell growth, differentiation and survival. Mutations in ras genes can lead to permanently activated proteins causing cells to subdivide without control.

The Nutritional Neuropharmacology Lab studies the molecular mechanisms and potential pharmacotherapeutic utility of G protein-coupled receptor (GPCR) biased signaling (a.k.a. functional selectivity), the process whereby receptors differentially or asymmetrically engage intracellular signaling pathways (e.g., G proteins, beta-arrestins) to elicit distinct physiological effects.

The GPCR superfamily is the largest class of membrane proteins in the human genome and the most common drug target of FDA-approved pharmaceuticals (>33%). GPCR biased signaling can be generated through ligand binding (biased ligands), receptor conformational states (biased receptors), and/or physical interactions with other proteins (biased complexes/oligomers).

To study GPCR-biased signaling, we use the growth hormone secretagogue receptor (GHSR) as its primary model. The GHSR is the cognate receptor for the endogenous hormones ghrelin and liver-expressed antimicrobial protein-2 (LEAP-2), and it is expressed highly in homeostatic (energy-based) and hedonic (reward-based) feeding circuits in the brain.

Gross Lab long term research goal illustration

This research seeks to determine how GHSR-biased signaling in these neurocircuits impacts diet choice/preference, food reward, diet-induced obesity, and metabolic physiology. We focus heavily on how the GHSR regulates brain dopamine signaling in these processes, particularly in response to obesogenic 'Western' diets.

A student wearing a lab coat and hairnet weighs cookies on a scale in a kitchen lab.

Students who are interested in our research and student lab opportunities should contact us to learn more.

Nutritional Sciences