Nagaraja Nagre
Old Dominion University, VA·Pharmacology
The lungs can be badly damaged by inhaling certain toxic chemicals, and for several of these there is no effective treatment. Two such chemicals are nitrogen mustard (NM), a blistering agent, and ammonia, a widely used industrial gas.
- Fields
Pharmacology
Physiology
Microbiology & Immunology
- Topics
acute lung injury
nitrogen mustard
ammonia
- Grants
- 2 known grants, through Jun 2028
What they work on
- Test how effectively inhibiting MAGL, the enzyme that degrades the endocannabinoid 2-AG, protects mice from nitrogen mustard-induced acute lung injury, inflammation and oxidative stress, using the selective inhibitor JZL184 and MAGL-inactivated animals.
- Delineate the mechanism of protection by MAGL inhibition in nitrogen mustard-induced lung injury, linking restored 2-AG signaling through cannabinoid receptors to reduced inflammatory and oxidative damage.
- Determine the extent to which MAGL inactivation changes lung injury, inflammatory response and toxicity after exposure to either nitrogen mustard or ammonia in a mouse pre-clinical model.
- Define the cellular and molecular responses to MAGL inactivation in lung immune cells, alveolar epithelial and endothelial cells, and human alveolar macrophages, to identify which cell types drive protection.
More about the research
Both can cause acute lung injury, and NM exposure can also lead to longer-term scarring (fibrosis), emphysema and small-airway disease. This research tests whether strengthening one of the body's own anti-inflammatory lipid signals can protect lung tissue after such an exposure.
Why it matters
Accidental releases of ammonia and exposure to nitrogen mustard can injure the lungs of workers, emergency responders and civilians, and no effective medical countermeasures currently exist. By testing whether blocking the enzyme MAGL protects lung tissue in mouse models and human cells, this work could identify a drug target for treatments or preventive therapies against chemical-induced acute lung injury.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Han Peng
Northwestern University, IL·Biology
Determine whether nitrogen mustard exposure frees Beclin1, a protein that starts autophagy, from its partner Bcl2 in corneal cells and mice, and whether changing this binding alters mustard-induced autophagy.
Yutong Zhao
Ohio State University, OH·Medicine & Clinical Research
Test whether blocking the mitochondrial deubiquitinase USP30 in endothelial cells reduces white blood cell adhesion and migration and preserves the vessel barrier, and whether deleting it lessens Pseudomonas- or sepsis-induced lung injury in mice.
Samithamby Jeyaseelan
Louisiana State University, LA·Microbiology & Immunology
Determine how the antioxidant regulator Nrf2 affects survival, bacterial clearance and neutrophil accumulation and function during carbapenem-resistant Klebsiella pneumoniae (CRKP) pneumonia in mice.
The school
Old Dominion University: 8 labs on PI Pages, $76M a year on research, 143 research doctorates a year.
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