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Research Projects

Stack Well B3 Phase

Fungi-skin Mutualistic Interactions

The mutualistic relationship between fungi and the human host remains understudied. While much work has gone into understanding the bacteriome, the mycobiome is an emerging area of importance. As such, some clinical studies have recognized that dysbiosis occurs in individuals with chronic inflammatory skin diseases (such as atopic dermatitis) and this is highlighted by the outgrowth of specific fungal species like Malassezia. We have observed that exposure of keratinocytes to certain commensal fungal strains, such as Candida albicans or Candida parapsilosis, can initiate enhanced barrier and diminished susceptibility to viral infection in keratinocyte cultures. Elucidating the mechanism behind these observations to better understand how fungi influence the skin in times of health and disease is one of the focuses of the lab.

S. Aureus Mechanisms of Pathogenesis in the Skin

The skin of patients with atopic dermatitis is frequently colonized with S. aureus, the abundance of which is associated with disease severity. Bacterial invasion of host cells is a mechanism which is thought to evade immune detection and/or establish long-term colonization, which would be an important parameter for disease management. This project aims to identify AD-relevant conditions that promote S. aureus invasion into keratinocytes and what pathways are necessary to enable this occurrence. Furthermore, how keratinocytes respond to invasion and limit infection/colonization is important in understanding methods to remove this potential long-term source of bacteria.

Susceptibility to Viral Infections Based on Skin Characteristics

How various characteristics of the skin (inflammation, barrier function, differentiation) alter susceptibility to viral infections from multiple cutaneous pathogens including vaccinia virus, herpes simplex viruses and varicella zoster virus. To address this complex question, we use a variety of model systems including disease simulating transgenic mice, as well as various in vitro models including primary and immortalized cells, organotypic (3D) cultures, and human tissue explants. With these systems we are able to determine the effect that various cytokines representative of different chronic cutaneous diseases (atopic dermatitis, psoriasis, lupus) have on viral infection parameters and use CRISPR/Cas9 to develop genetically modified cells that simulate specific characteristics of these diseases. The goal is to better understand what determines an individual's risk of severe viral infections and identify therapeutic interventions that can help mitigate severe disease.