Amanda M. Nelson, PhD
Penn State University College of Medicine
Hershey, PA
2022 Research Scholar Award Recipient
Identifying a Transcriptomic Signature for Acne Susceptibility as a Tool to Enhance Drug Discovery
Abstract
Acne is a complex inflammatory skin disease and while the factors contributing to acne pathogenesis are well described, the factors that predispose individuals to develop acne are less clear.
Our compelling preliminary data led us to hypothesize that the genes that are differentially expressed between non-lesional acne skin and skin from healthy subjects may contribute to acne susceptibility and correlate with degree of acne severity. We made the novel discovery that 68 genes are differentially expressed between non-lesional skin of acne patients and skin from individuals without acne. Collectively, these differentially expressed genes have important roles in maintaining the structure and function of a healthy hair follicle or pilosebaceous unit. A key question is whether these skin-specific gene expression alterations in acne skin contribute to acne susceptibility and/or degree of disease severity in acne patients.
Acne is a complex inflammatory skin disease resulting from the interplay between follicular plugging, sebum production, C. acnes activities and skin inflammation. Skin-specific gene expression differences may explain the susceptibility to acne, as the site of acne pathogenesis is the pilosebaceous unit. We propose that altered gene expression within non-lesional skin of acne patients “primes” the skin and pilosebaceous units to develop an acne lesion when other acne stimuli are present.
In this proposal, we will use 94 existing RNA-sequencing datasets from the skin of acne subjects and subjects without acne to identify a gene expression signature for acne susceptibility as a tool to enhance drug discovery. These datasets are annotated with acne severity scores (IGA scores) and are generated from non-lesional, clinically normal skin allowing us to determine if there are underlying differences in gene expression that could explain an individual’s predisposition to develop acne.
Impact: The outcomes from this work will increase our understanding of acne skin and can be used to identify novel treatments to interrupt the pathways leading to acne development.