# Translation & trials: advancing medical countermeasure development

> **NIH NIH U54** · NORTHWESTERN UNIVERSITY · 2024 · $648,570

## Abstract

Mustard gas and mustard-related compounds are alkylating agents that cause severe epithelial and deep tissue
injury characterized by acute inflammation, induration, edema, and blistering upon contact. The underlying
mechanism of tissue damage following exposure to nitrogen mustard (NM) and sulfur mustard (SM) is complex.
After the initial direct injury to the skin there is an influx of immune cells that provide a defense to a breached
epithelium but can produce unfavorable inflammation culminating in an immune storm that sets off a cascade of
tissue injury. Historic use of SM demonstrates that the consequences extend beyond surfaces of the skin. Our
group has shown by suppressing activated macrophages systemically with high dose vitamin D can ameliorate
both local skin and deeper tissue injury. Given that the totality of injury from mustard exposure is attributable to
the toxic agent and the activities of the immune system, it may be naive to consider that a single countermeasure
can adequately and comprehensively mitigate the effects of mustard. We will leverage our experience with NM
and SM, and access to banked tissue from in vivo NM exposure in humans and SM in large animals, to serve as a
foundation to unravel the signals in the skin compartment vs. the immune compartment. Mustard exposed skin
explants will be immunophenotyped and the harvested culture supernatants will be used to stimulate activation of
naïve peripheral blood immune cells. Our human Mustard Skin Explant and Supernatant (MuSES) experimental
setup approximates features of human skin in vivo, exposed to SM and will enable studies that delineate
inflammatory factor production by the skin and immune compartments. Inflammation profiles from MuSES will be
validated using tissue from our in vivo human clinical trials in patients undergoing field treatment for precancerous
skin treatments. Given the remarkable resemblance of the skin phenotype reaction, we can gather information
from in vivo human exposure models to test our two countermeasures . Clinical outcomes coupled with novel
signature molecular targets will facilitate proof-of-concept (POC) clinical trials in 5-FU patients (delayed start to
years 3-5). Our countermeasure strategies are to block the activation of skin infiltrating immune cells with vitamin
D3 or block their entry into the skin with PLGA-immune modifying microparticles. This combined approach is aimed
at limiting the surge of cytokines and inhibiting downstream tissue matrix factors released in the skin. The goals
of this project are to better understand reactions of the skin and immune system using a combination of human
tissue and trials to develop medical countermeasures.

## Key facts

- **NIH application ID:** 10907618
- **Project number:** 5U54AR079795-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Kurt Lu
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $648,570
- **Award type:** 5
- **Project period:** 2021-09-17 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10907618

## Citation

> US National Institutes of Health, RePORTER application 10907618, Translation & trials: advancing medical countermeasure development (5U54AR079795-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10907618. Licensed CC0.

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