Dr. Moniri’s research interests focus on pharmacology and biochemistry of G protein-coupled receptors (GPCRs).  These cell-surface receptors comprise the largest gene family in the human genome and also represent  the largest class of drug targets, accounting for roughly 40-50% of drugs used clinically today.  By coupling intracellularly to heterotrimeric G proteins, GPCRs are able to  transduce signals from a variety of extracellular stimuli, including neurotransmitters, hormones, and sensory stimuli.

Dr. Moniri's laboratory currently has two major research projects.  The first is focused on novel signaling pathways of the β₂-adrenergic receptor (AR).  Our laboratory  has shown that agonist-stimulation of β₂AR leads to generation of intracellular reactive oxygen species (ROS), formation of which is required for G protein dependent signaling.  We have also recently demonstrated that ROS are capable of feeding back to oxidize β₂AR cysteine residues to S-Sulfenic acids, suggesting ROS-mediated post-translational modification of the receptor.  Most recently, we have demonstrated that ROS are required for β₂AR interactions with β-arrestins and β-arrestin dependent signaling.  We are interested in further understanding the impact of ROS on β₂AR signaling in disorders of the lungs, heart, and kidneys, which express high densities of β₂AR.  This project relies heavily on in vitro pharmacology and molecular biology, as well as medicinal chemistry.

The Moniri laboratory is also interested in GPCRs which are attractive targets for pharmacotherapy of neuro-endocrine disorders. Recent evidence implicates several newly “deorphanized” GPCRs as important participants in the physiological regulation of insulin secretion, as well as regulation of caloric intake and satiety.  While the GPCRs involved have been identified and linked to these downstream physiological functions, the molecular intracellular pharmacology and receptor biochemistry which drives endocrine activity remains elusive.  Research projects in Dr. Moniri’s lab are directed towards characterization and elucidation of intracellular signaling pathways associated with these GPCRs, in particular, the long chain free-fatty acid receptor, FFA4, also known as GPR120. 

Specifically, FFA4 agonism has been linked to secretion of glucagon-like peptide-1 (GLP-1) and downstream insulin release, and has also been shown to play major roles in thwarting insulin resistance, inflammation, and  weight gain, suggesting importance of this receptor in etiology of type-2 diabetes and obesity.  Our laboratory is interested in FFA4 regulation, particularly with respect to phosphorylation. 

Identification and characterization of potential endogenous or dietary ligands, as well as development of novel synthetic ligands, along with characterization of FFA4 biochemistry and intracellular signaling cascades will provide a mechanistic basis for rationale drug design to treat disorders such as diabetes and obesity.  Projects will encompass a broad spectrum of biomedical and pharmaceutical sciences including in vitro and in vivo pharmacology, molecular biology, biochemistry and medicinal chemistry.

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