# Keratinocyte targeted strategies for treatment of cutaneous GVHD

> **NIH NIH R21** · DUKE UNIVERSITY · 2020 · $175,088

## Abstract

ABSTRACT
Graft-versus-host disease (GVHD) is a common complication and the leading cause of non-relapse mortality
among patients after receiving allogenic hematopoietic stem cell transplantation. The skin is the most
commonly affected organ in both the acute and chronic forms of this disease. Treatment options are limited,
and the current standard therapy is high dose systemic corticosteroids, which is in itself associated with
significant morbidity and mortality. There is therefore a great need for novel treatment options for cutaneous
GVHD. While the exact cause of GVHD is unclear, it involves a complex interaction between the donor
immune cells and the recipient cells. Studies to date are primarily focused on immune cells. Little is understood
about the role of recipient cells such as keratinocytes that form the principal barrier of the skin and oral
mucosa. Our preliminary studies show that MEK is highly activated in keratinocytes of GVHD skin and oral
lesions and that keratinocyte-targeted MEK activation in mice results in the development of a range of skin and
oral lesions resembling those of human GVHD. These findings lead us to hypothesize that MEK activation in
skin cells plays a major role in the development of cutaneous GVHD and that topical MEK-inhibition can be
topically targeted for therapy. To test these hypotheses, we propose two specific aims: 1) to determine the
effects of topical MEK-inhibition on preclinical models of GVHD; 2) to establish the utility of pMEK and its
downstream targets as skin-based biomarkers for GVHD. We anticipate that completion of this study will lead
to the development of skin-based biomarkers and novel topical treatment strategies that may benefit many
transplant patients.

## Key facts

- **NIH application ID:** 9834851
- **Project number:** 5R21CA223419-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Adela Rambi Cardones
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $175,088
- **Award type:** 5
- **Project period:** 2018-12-10 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9834851

## Citation

> US National Institutes of Health, RePORTER application 9834851, Keratinocyte targeted strategies for treatment of cutaneous GVHD (5R21CA223419-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9834851. Licensed CC0.

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