# Research Project  I - Vesicant-Induced Skin Injury

> **NIH NIH U54** · RBHS-SCHOOL OF PUBLIC HEALTH · 2020 · $846,767

## Abstract

Research Project 1. Vesicant-induced Skin Injury
Key personnel:
Donald Gerecke, Ph.D., Associate Professor, Rutgers University School of Pharmacy
Jeffrey D. Laskin, Ph.D., Professor, Rutgers University School of Public Health
Project Summary/Abstract
Sulfur mustard (bis-2-chloroethyl sulfide, SM) and nitrogen mustard (bis-2-chloroethyl ethylamine, NM), are
vesicants that have been adapted for use as chemical weapons; they are potent blistering agents in the skin.
The overall goal of this research project is to elucidate basic mechanisms of mustard damage to the skin with
the objective of identifying new targets for therapeutic intervention and drug development. We discovered a
highly novel link between skin injury and inflammation induced by vesciants and the endocannabinoid system,
a ubiquitous signaling system that regulates cell growth and differentiation and down regulates inflammatory
responses. Endocannabinoids consist of endogenous ligands (e.g., anandamide [AEA] and 2-arachidonoyl-
glycerol, [2-AG]), cannabinoid receptors (e.g., the G-protein coupled CB1 and CB2 receptors), and metabolic
enzymes that regulate endocannabinoid biosynthesis (e.g., N-acyltransferases, phospholipases) and
degradation (e.g., fatty acid amide hydrolase [FAAH], monoacylglycerol lipase [MAGL]). Topical application of
either SM or NM to mouse skin caused a marked and persistent upregulation of expression of the
endocannabinoid degrading enzyme, FAAH, and receptor proteins that bind endocannabinoids including CB1,
CB2 and peroxisome proliferator-activated receptor-α (PPARα). Importantly, endocannabinoids have been
shown to accumulate in human skin blister fluid, suggesting that they may be involved in the pathophysiologic
response to vesicants. We hypothesize that endocannabinoids regulate inflammation and wound healing in the
skin following exposure to mustards and thus, the endocannabinoid system can be targeted for the
development of countermeasures. Our key lead product entering advanced development is an inhibitor of
FAAH. Our aims are to assess the role of the endocannabinoid system in vesicant-induced skin injury and
wound healing and elucidate mechanisms by which mustards modulate keratinocyte expression of the
endocannabinoid system. We will also evaluate a highly novel drug delivery system to improve efficacy of our
lead compound. Our studies will provide key information on the role of endocannabinoids in the
pathophysiology of vesicant-induced skin toxicity and lead to the development of more effective
countermeasures.

## Key facts

- **NIH application ID:** 9982788
- **Project number:** 5U54AR055073-15
- **Recipient organization:** RBHS-SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** DONALD R GERECKE
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $846,767
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982788

## Citation

> US National Institutes of Health, RePORTER application 9982788, Research Project  I - Vesicant-Induced Skin Injury (5U54AR055073-15). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9982788. Licensed CC0.

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