Contact Information:

  3001 Mercer University Dr

  239 Moye Center

  Atlanta, GA 30341

  (678)-547-6246

  moniri_nh at mercer.edu

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. 

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.  We are interested in further understanding the impact of ROS on β2AR signaling within physiological systems, particularly in the human airway. This NIH-funded project relies heavily on in vitro pharmacology and molecular biology, as well as medicinal chemistry and seeks to examine the role of the ROS-β2AR in human airway tissue and in disease state such as asthma and COPD.

The role of FFA receptors in human health and diseases

We are currently investigating the role of FFA receptors, namely FFA1/GPR40 and FFA4/GPR120, which are agonized by long-chain FFA inlcuding omega-3, omega-6, and omega-9 fatty acids in a variety of human systems, including neurodegenerative diseases, such as Parkinson's Disease, pulmonary diseases such as asthma, as well as in cancers. We are also very interested in the short-chain FFA receptors FFA2/GPR43 and FFA3/GPR41, particularly their roles in mediating the functions of the gut microbiome, which generate SCFA. These projects rely heavily on in vitro pharmacology and molecular biology.

Molecular pharmacology of the drug of abuse xylazine

Illicit use of the surgical anesthetic xylazine has grown dramatically and over the last few years alone, the illicit use of xylazine-adulterated opioids, including fentanyl, has increased exponentially, which has resulted in a variety of public health concerns, including necrosis of the skin. In collaboration with Dr. Clint Canal's laboratory, a recent NIH grant supports a project that seeks to fully characterize the molecular pharmacology of xylazine at α-adrenergic receptors. This research can shed light on the cellular mechanisms of xylazine that may cause skin damage as well as other peripheral effects.

Selective muscarinic acetylcholine receptor drug development

Dr. Moniri and Dr. Canal are co-founders of Channel Therapeutics, LLC, a drug development startup that seeks to discover and develop selective muscarinic acetycholine receptor (MAChR) antagonists for clinical therapy of a variety of disease states including Parkinson's disease, urinary tract and gastrointestinal disorders, and airway disorders. Channel Therapeutics portfolio of patented compounds is being developed to be highly selective for one subtype of MAChR subtype over the other four subtypes, reducing the side effect potential of these novel anticholinergic agents.