2017 ODAC conference ARTE poster winner

Bioinformatics analysis of the inflammatory acne transcriptome supports mechanisms of action for current treatments and predicts novel therapies in vivo

Rivka C. Stone, Marjana Tomic-Canic

Research output: Contribution to journalArticle

Abstract

Acne vulgaris, a common disorder of pilosebaceous follicles, adversely affects quality of life in patients. Formation of papules and pustules in inflammatory acne is orchestrated by a sustained host immune response whose features are incompletely understood, impeding the development of novel targeted therapies. To this end, we utilized transcriptome data previously obtained from lesional and non-lesional skin of 18 patients with inflammatory acne. We identified an acne "signature" of 217 genes that were coordinately up-or down-regulated in lesional skin of patients from two cohorts. Pathway analysis was enriched for biological processes of innate and adaptive immunity. We employed bioinformatics techniques to identify drugs predicted to target acne-relevant immune processes through their known effects on the expression of subsets of inflammatory acne "signature" genes. Using this approach, we linked minocycline to modulation of neutrophil and lymphocyte migration via its downregulation of IL1B, IL6, CXCL8, and CCR2 expression that is increased in lesional acne skin in vivo. Similar networks were constructed for tretinoin and salicylic acid therapies. Finally, we predicted a novel role for small molecule inhibitors of MEK/ERK signaling in the treatment of inflammatory acne. Taken together, our findings suggest that bioinformatics approaches can be successfully employed in the discovery an development of acne therapeutics.

Original languageEnglish (US)
Pages (from-to)1166-1169
Number of pages4
JournalJournal of Drugs in Dermatology
Volume16
Issue number11
StatePublished - Nov 1 2017

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Posters
Acne Vulgaris
Computational Biology
Transcriptome
Therapeutics
Skin
Biological Phenomena
Minocycline
Salicylic Acid
Mitogen-Activated Protein Kinase Kinases
Adaptive Immunity
Tretinoin
Innate Immunity
Genes
Interleukin-6
Neutrophils
Down-Regulation
Quality of Life
Lymphocytes

ASJC Scopus subject areas

  • Dermatology

Cite this

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title = "2017 ODAC conference ARTE poster winner: Bioinformatics analysis of the inflammatory acne transcriptome supports mechanisms of action for current treatments and predicts novel therapies in vivo",
abstract = "Acne vulgaris, a common disorder of pilosebaceous follicles, adversely affects quality of life in patients. Formation of papules and pustules in inflammatory acne is orchestrated by a sustained host immune response whose features are incompletely understood, impeding the development of novel targeted therapies. To this end, we utilized transcriptome data previously obtained from lesional and non-lesional skin of 18 patients with inflammatory acne. We identified an acne {"}signature{"} of 217 genes that were coordinately up-or down-regulated in lesional skin of patients from two cohorts. Pathway analysis was enriched for biological processes of innate and adaptive immunity. We employed bioinformatics techniques to identify drugs predicted to target acne-relevant immune processes through their known effects on the expression of subsets of inflammatory acne {"}signature{"} genes. Using this approach, we linked minocycline to modulation of neutrophil and lymphocyte migration via its downregulation of IL1B, IL6, CXCL8, and CCR2 expression that is increased in lesional acne skin in vivo. Similar networks were constructed for tretinoin and salicylic acid therapies. Finally, we predicted a novel role for small molecule inhibitors of MEK/ERK signaling in the treatment of inflammatory acne. Taken together, our findings suggest that bioinformatics approaches can be successfully employed in the discovery an development of acne therapeutics.",
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