# Targeting early ceramide elevation in pre-symptomatic eczema

> **NIH NIH P20** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2022 · $178,619

## Abstract

The prevalence and incidence of atopic dermatitis (AD), most common type of eczema, have increased 
over the last several decades, as AD remains the most common chronic inflammatory skin disease. AD is 
characterized by widespread pruritic skin lesions, making it the skin disorder with the highest disease 
burden globally. The mechanisms leading to skin barrier disruption and overt lesions are ill defined. While 
some studies focus on T cell-derived cytokines as possible underlying effectors of disrupted skin, we 
reasoned that T cells may be preceded by mast cells as first-line effector cells as mast cells are skin 
resident immune cells facilitating T cell recruitment. Moreover, many AD studies are comparing features of 
lesional to neighboring non lesional skin samples, i.e., when the diseased state is already established, we 
used a preclinical human AD-like model to investigate the pathogenic events leading to overt lesions. We 
recently reported an early elevation of ceramide sphingolipids in skin samples treated with an 
AD-triggering antigen, compared to controls, that was driven by mast cells, enabling early cutaneous 
apoptosis through endoplasmic reticulum (ER) stress. In this proposal, we offer to investigate the 
contribution of ceramides and apoptosis in AD pathogenesis in another preclinical AD model and the 
effects of resveratrol, a natural compound, on restoring homeostatic ceramide metabolism to attenuate 
ER stress, apoptosis and subsequent loss of skin integrity. The objectives of this application are: To 
investigate the effects of resveratrol on early ceramide elevation and apoptosis in preclinical AD, and to 
study the impact of antigen exposure on human skin explants and the regulatory functions of resveratrol. 
We anticipate that our proposed studies will contribute to a better understanding of AD pathogenesis and 
the mechanisms of action of resveratrol. We are proposing that these studies will identify actionable 
pathogenic pathways preventing AD disease progression.

## Key facts

- **NIH application ID:** 10665481
- **Project number:** 5P20GM103641-10
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** Mitzi Nagarkatti
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $178,619
- **Award type:** 5
- **Project period:** 2022-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10665481

## Citation

> US National Institutes of Health, RePORTER application 10665481, Targeting early ceramide elevation in pre-symptomatic eczema (5P20GM103641-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10665481. Licensed CC0.

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