My research focuses on the intersection between chronic inflammatory skin diseases (such as atopic dermatitis and psoriasis) and the underlying immune environment during times of stimulation (such as vaccination) and disease (both viral and bacterial pathogens).
Utilizing the skin as the primary site of antigen delivery represents an underappreciated practice in vaccine biology. To correct this lack of knowledge, I am working on methods enabling antigen delivery into the epidermis. My unique approach targets a microdomain in the epidermis called tight junctions, which serve as a critical source of skin barrier. I have demonstrated that disruption of tight junctions via a targeted peptide delivers influenza antigens into the skin and elicits an anti-influenza humoral response similar to intramuscular delivery. Ongoing studies include how this technology alters the cellular and inflammatory environment of the skin. Importantly, antigen type (protein, carbohydrate, lipid) and source (bacterial, viral, protozoan) can cause alterations in acquisition, processing, and presentation from different cell types of the immune system. Whether these attributes affect the efficacy of an immune response initiated in the skin are unknown and the focus of ongoing studies. Finally, drug delivery into the epidermis represents a safer route due to diminished side effects, which typically arise after systemic delivery. Unfortunately, drug delivery into the skin is usually inefficient because of the molecular characteristics of most therapeutics. Current studies using small molecule inhibitors delivered into the skin by tight junction disruption are expected to support this technique as a method to enhance cutaneous drug delivery and decrease the necessity of oral or intravenous routes.
Individuals with chronic inflammatory skin diseases have been shown to be overly susceptible to bacterial and viral infections. The underlying mechanism behind this occurrence is poorly understood. To address this gap in knowledge, my group has developed a number of models including CRISPR/Cas9 knockout cell lines, primary cell cultures from neonatal/adult skin tissue, a mouse AD model, and an adult skin explant infection platform. I focus my viral pathogenesis studies on skin-specific viruses (vaccinia and herpes simplex, respectively). In addition, I have been studying how bacterial pathogens (S. aureus, S. epidermidis, etc.) are able to invade, persist, and disseminate in the skin. These studies are expected to identify host factors or pathways in epidermal cells (i.e. keratinocytes) that are critical for protection against or susceptibility to pathogens, which would open up new druggable targets to prevent cutaneous infections.