University of North Carolina at Chapel Hill
Helen Lazear, PhD
Assistant Professor, Dept. of Microbiology & Immunology
Victoria Baxter, DVM, PhD, DACLAM
Assistant Professor, Dept. of Pathology & Laboratory Medicine, Biocontainment Veterinarian and Head of Animal Health Surveillance, Division of Comparative Medicine
Hannah Atkins, DVM, PhD, DACVP
Assistant Professor, Dept. of Pathology & Laboratory Medicine, Veterinary Pathologist
Zhi Liu, PhD
Professor, Dept. of Dermatology
Description of Potential Research Projects
Dysregulation of the cutaneous barrier is a key feature of dermatological conditions such as atopic dermatitis, also called eczema. Atopic dermatitis patients are susceptible to severe skin infections, including with herpes simplex virus type 1 (HSV-1) (eczema herpeticum). Type III interferons (IFN-λ) provide front-line protection at anatomic barriers, controlling infections locally and minimizing inflammatory immune pathology, but the effects of IFN-λ at the skin barrier have not been studied extensively. We found that mice lacking IFN-λ signaling (Ifnlr1-/-) developed more severe HSV-1 skin infection compared to wild-type mice; ongoing work in our lab seeks to define the IFN-λ dependent mechanisms that limit HSV-1 replication and skin disease, using conditional knockout mice that lack IFN-λ signaling in specific cell types.
In addition to its antiviral effects, we hypothesize that IFN-λ signaling in keratinocytes strengthens the epithelial barrier and limits the inflammatory pathology of atopic dermatitis. In this project, we will evaluate atopic dermatitis disease in WT and Ifnlr1-/- mice and define the IFN-λ-responsive cell types that limit atopic dermatitis disease. We will evaluate skin barrier permeability in Ifnlr1-/- mice using in vivo permeability assays and in primary keratinocytes. We will evaluate the severity of HSV-1 skin infection in mice with atopic dermatitis, and the ability of IFN-λ to ameliorate HSV-1 pathogenesis in the context eczema herpeticum. This project also would provide an opportunity to investigate the effects of IFN-λ in the context of other skin pathologies or to extend these observations into other animal models of skin inflammation or skin infections.
Additional Training Opportunities
The fellow will have the opportunity to engage with the extensive and supportive training environment in the UNC Department of Microbiology & Immunology and the Lazear Laboratory. In addition to regular interactions with outstanding colleagues and collaborators, M&I Department activities include a weekly seminar with invited faculty speakers, and weekly work-in-progress seminars where students and postdocs present their research. The fellow also will have access to the UNC Chapel Hill Office of Postdoctoral Affairs, which offers a variety of services to enhance, support, and promote postdoctoral training and help to prepare postdoctoral scholars for successful research careers. The fellow will have the opportunity to present their work at local and national meetings and to work with the primary mentor to develop manuscript and grant writing skills. In addition to engaging with the virology and immunology research of the Lazear Lab, the fellow will also have opportunities to engage with a team of veterinary pathologists and lab animal veterinarians through the Division of Comparative Medicine.