Date of Award

2026

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Bioinformatics & Computational Biology

First Advisor

Michael Burns

Abstract

The skin microbiome is a critical modulator of wound healing, inflammation, and dermatological disease progression. This work focuses on S. aureus, which interfaces with host skin cells to drive inflammation and increase risk of bacteremia and mortality. Despite this microbe’s prevalence in skin and soft-tissue infection, precise Staphylococcus characterization has only become possible with recent advances in metagenomic sequencing. Applying increasingly high-resolution and multi-omics approaches, S. aureus was investigated in this work as a driver of outcomes across cutaneous T-cell lymphoma (CTCL), epidermolysis bullosa (EB), and erythroderma. In Aims 1 and 2 of this thesis, microbial states were profiled using short-read and long-read 16S rRNA gene amplicon sequencing to identify shifts driven by racial disparities and microbiome-targeted therapeutics. In Aims 3, 4, and 5, analyses expanded from microbial associations to direct integration of microbial changes with host gene expression. Using a novel combination of long-read 16S metagenomics and NanoString GeoMx spatial transcriptomics, the immune-microbial landscape was profiled across a mixed-diagnosis cohort of inflammatory skin disorders. Through this multi-scale analysis, clinically targetable immune pathways, including NOD2, were associated with high S. aureus and low microbial diversity across inflammatory conditions. Inflammatory keratin upregulation in pathogenically-colonized skin also reinforced previous knowledge of the interactions between skin barrier breakdown and S. aureus. Lastly, indicators of sepsis risk, including downregulated FLOT2, were associated with high S. aureus in our cohort. These results reinforced the interplay of inflammation, skin barrier breakdown, and pathogenic colonization in complex skin disease. Collectively, this work supports development of precision treatment strategies, targeting both immune and microbial axes of skin disease to reduce inflammation, prevent infection, and improve outcomes.

Available for download on Wednesday, July 19, 2028

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