_     _
 
     
HomeResearchCoursesMercer COPMercer HSCLinks

 
 
 

 

  Contact Information:

  3001 Mercer University Dr

  122 Duvall Bldg

  Atlanta, GA 30341

  (678)-547-6246

  moniri_nh@mercer.edu

 

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.

 

   
     

  Laboratory Research Focus Areas:

 

Project 1 - The role of phosphorylation in regulating the antidiabetic effects of FFA4 (GPR120)

 
 

FFA4, formerly referred to as GPR120, is a recently indentified unsaturated free-fatty acid receptor that recognizes long-chained fatty acids, including the omega-3-fatty acids a-linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA).  Agonism of FFA4 has been shown to promote profound anti-inflammatory and antidiabetic effects.  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.  As such, FFA4 has drawn considerable interest as a target for treatment of type-2 diabetes and obesity. 

Through NIH-funded grant support, our laboratory is interested in studying the mechanisms by which FFA4 is regulated.  In particular, our laboratory is interested in studying the role that FFA4-phosphorylation plays in regulating its anti-inflammatory and antidiabetic effects.

In addition, we are interested in identification and characterization of potential endogenous or dietary ligands, as well as development of novel synthetic ligands as modulators of FFA4 function.  These efforts, 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. 

 

 
 

 

Project 2 - β2-Adrenergic Receptors and Reactive Oxygen Species

 
 

The β2-adrenergic receptor (β2AR) is one of the best characterized GPCRs, mediating physiological responses to epinephrine and norepinephrine.  Many β2-receptor acting agents are utilized in the clinical therapy of asthma, COPD, and emphysema.  While the effects of activation of β2-receptors have been studied in great detail, our laboratory is interested in a more recently linked aspect of β2-receptor signaling, namely, generation of reactive oxygen species (ROS). 

Our studies have shown that agonist-stimulation of β2AR leads to generation of intracellular 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. Through another NIH-funded grant, we are currently examining the β2AR-ROS linkage in airway function.  This project relies heavily on in vitro pharmacology and molecular biology, as well as medicinal chemistry.

 
   
 

 

Project 3 - Cross-talk between Histamine H1 and β2-Adrenergic Receptors in Pulmonary Smooth Muscle

 
  Agonism of histamine H1 receptors on the smooth muscles of the lung causes their constriction, leading to airway disorders such as asthma. This effect can be treated utilizing agents that cause relaxation of the pulmonary smooth muscle, for example, β2-adrenergic receptor agonists.  However, the effectiveness of such treatment is often short-lived and eventually requires addition of other agents to maintain the benefit. 

In this project, we are interested in examining the molecular interplay between H1R and β2AR in pulmonary smooth muscle, particularly in tissue that is chronically challenged with H1R or β2AR agonists.  These studies will aid in our molecular understanding of the long term treatment of bronchial tissue with β2-agonists.  This project relies on molecular pharmacology and molecular biology.
 
                                                                                                                                                                                                           
Last Updated: 7/20/2017
Copyright 2019İMercer University
All Rights Reserved