Study Pierces a Mystery of Healthy Skin Barrier Formation
Research By: Stanley DeVore, PhD | Gurjit Khurana Hershey, MD, PhD
Post Date: August 7, 2024 | Publish Date: Aug. 6, 2024
Asthma Research | Top Scientific Achievement
Experts at Cincinnati Children’s have discovered a novel signaling pathway that opens new doors to treating atopic dermatitis and psoriasis, and may have impacts beyond skin disease
Our skin–the body’s largest organ–provides the first line of defense against infections and many other threats to our health. Decades of research has shown that a wide range of diseases can occur, or become worse, when the skin cannot form an effective barrier.
Now, experts in human genetics and asthma research at Cincinnati Children’s report the discovery of a novel molecular signaling pathway that is critical for maintaining a healthy skin barrier. These far-reaching findings may eventually lead to new ways to prevent and treat inflammatory skin diseases such as atopic dermatitis (AD, or eczema) and psoriasis.
The study was published online Aug. 6, 2024, in Cell Reports, and builds off of from the early-life prospective cohort of children with atopic dermatitis. The team of 22 co-authors was led by first author Stanley DeVore, MD, PhD, and corresponding author Gurjit Khurana Hershey, MD, PhD.
“Our research discovered a previously unknown cellular pathway involving the protein CARD14,” DeVore says. “When this protein works properly, it keeps our skin barrier healthy, but when CARD14 is not working properly, it promotes the development of skin disease.
“We found that CARD14 directly binds and regulates MYC, a protein involved in controlling cell growth that can contribute to cancer when it malfunctions. Our study shows that the proper interaction between these two proteins is important for a healthy skin barrier and protecting against eczema and psoriasis.”
Shedding old skin for a clearer view
Previous research focused on the CARD14-NFκB signaling pathway, which is thought to promote psoriatic diseases when elevated and eczema when reduced. Millions of people are affected by these and other inflammatory skin disorders.
“However, that model does not fully explain the variability in CARD14-driven diseases,” says Hershey, who directs the Division of Asthma Research at Cincinnati Children’s. “This new CARD14-MYC signaling pathway strengthens the link between CARD14 and skin barrier health.”
Study co-authors say that CARD14 regulates skin barrier function through two mechanisms: stimulating NFκB to establish an antimicrobial barrier and stimulating MYC to help build a physical barrier. Together, these CARD14-driven mechanisms provide a clearer understanding of how CARD14 supports skin health.
Barrier protection that goes deeper than the skin
The study further explores how various mutations in CARD14 can promote different allergic diseases, not only eczema and psoriasis.
Importantly, the study reports that mutations in CARD14 could affect MYC signaling which may lead to barrier function impairment and diseases in other tissues. For example, mutations that reduce CARD14’s ability to stimulate MYC signaling may lead to leaks in barriers other than the skin such as in the airway or the digestive tract, contributing to asthma or eosinophilic esophagitis, respectively. However, a mutation that increases CARD14-driven MYC signaling may increase cell growth and proliferation which, under the right circumstances, may lead to cancer.
Next steps
DeVore says the hunt is on to identify small-molecule agents that can safely influence the CARD14-MYC pathway. In fact, aspects of the study have led to the publication of an international patent application.
“Our ultimate goal is to develop novel therapeutics,” DeVore says. “We also are conducting studies aimed at identifying cancers that may be affected by CARD14-MYC signaling.”
Recently, the team published a perspective review in Frontiers of Molecular Medicine in November 2025 exploring how CARD14’s protein family can affect MYC in other cell types.
In the meantime, co-authors continue to investigate how MYC and CARD14 directly interact, and how mutations in CARD14—and other proteins in its family—can lead to other allergic diseases and cancer.
About the study
Co-authors from Cincinnati Children’s include Matthew Schuetz, BS; Lauren Alvey, BS; Henry Lujan, PhD; David Ochayon, PhD; Lindsey Williams, BS; Wan-Chi (Daisy) Chang, MS; Alyssa Filuta, MS; Brandy Ruff, BS; Arjun Kothari, MEng; Eric Brandt, PhD; Latha Satish, PhD; Krishna Roskin, PhD; Andrew Herr, PhD; Jocelyn Biagini, PhD; and Lisa Martin, PhD.
Funding sources for this work include the National Institutes of Health (U19AI70235, T32GM063483, R01AI162964, and T32ES010957). The Cincinnati Children’s Research Flow Cytometry Facility, Bio-Imaging and Analysis Facility, Integrated Pathology Research Facility, and Genomics Sequencing Facility also contributed.
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| Original title: | Regulation of MYC by CARD14 in human epithelium is a determinant of epidermal homeostasis and disease |
| Published in: | Cell Reports |
| Publish date: | Aug. 6, 2024 |
Research By
My lab combines epidemiologic, basic, translational and clinical research approaches to answer fundamental questions related to childhood asthma, atopic dermatitis, food allergy and allergic rhinitis.
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The Research Horizons blog features news and insights about the latest discoveries and innovations developed by the scientists of Cincinnati Children's. This blog does not provide medical advice, diagnosis, or treatment. Email researchnews@cchmc.org with questions or ideas.
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