Research Projects

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

S. aureus colonization has been shown to be associated with multiple skin disease including atopic dermatitis, psoriasis, and most recently the autoimmune blistering disease bullous pemphigoid. How this bacterium influences disease severity and/or exacerbation during times of remission remains poorly understood. Two characteristics of this bacteria that our lab is interested in is invasion of host cells, because this event facilitates evasion of the immune system and establishment of long-term colonization, and bacterial virulence factor production. Our studies have indicated that keratinocyte differentiation status and the inflammatory environment are critical factors in bacterial invasion. Additionally, our new studies on bullous pemphigoid have indicated that virulence factors play a key role in the biology of the main autoimmune target (BP180) in this disease. Going forward our goal is to establish the important parameters of the skin that S. aureus modulates to initiate/exacerbate these various skin disease states.

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.