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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.
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Dr. Moniri's laboratory currently has two major
research projects. The first is focused on
novel signaling pathways of the b2-adrenergic
receptor (b2AR). In a recent
manuscript appearing in Biochemical Pharmacology, we showed
that agonist-stimulation of b2AR leads
to generation of intracellular reactive oxygen species (ROS),
formation of which is required for receptor function.
Currently, we are examining the molecular mechanisms of
b2AR-mediated ROS formation, and the
effects of various adrenergic ligands on b2AR-mediated
ROS generation. These results could have a profound impact
on the understanding of oxidative stress in disorders of the lungs,
heart,
and kidneys, which express high densities of b2AR.
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,
identification and characterization of potential endogenous or
dietary ligands, as well as development of novel synthetic ligands.
Characterization of receptor 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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