Dr. Kinchington has long been interested in viruses that cause blinding infections in the eye. He was trained as a molecular virologist and studies virology with ophthalmology in his research.
- Uniformed Services University of The Health Sciences, Bethesda, MD, Postdoctoral Fellowship
- University of Leeds, PhD in Microbiology
- University of Leeds, BSc (Honors) in Microbiology
Education & Training
Dr. Kinchington has had the opportunity to collaborate with vision researchers by directing a “Molecular Biology module” of an NEI-funded Center of Research Excellence (CORE) NIH award for 30+ years. The module provides technical expertise to vision researchers without the skills or resources to do molecular biology. Other modules help with qualitative imaging, histology, tissue culture, flow cytometry, and fabrication of “widgets.” This module is exceptionally skilled in making multiple viruses for use as vectors that can deliver genes or modulate the expression of a host protein to identify its functions. All these modules have permitted many NEI-funded researchers and Investigators to advance their programs in ways that might not have happened otherwise.
Most of the work currently addresses VZV, a virus that can infect and cause disease in virtually any part of the eye. The virus is quite challenging to work with: outside of humans, it does not grow well in culture, primarily restricted to human cells, and the progeny virus remains tightly associated with the producing cell. Its human specificity precludes small animal modeling of eye infection, disease, and pathogenesis. Dr. Kinchington is one of a few researchers with the expertise to grow, manipulate, and study this virus’ biology.
The lab has three VZV projects. The first is to understand why VZV causes debilitating pain, which is a frequent and severe complication of Herpes Zoster in humans. The lab developed a footpad pain model and now has an exciting new facial pain model that mimics aspects of the ocular pain that grows in many facial shingles patients. These models are not only used to examine underlying mechanisms but also to evaluate new pain-relieving treatments.
The second VZV project is to understand how the virus infects and maintains itself in sensory neurons for decades, only to reawaken and cause shingles. The lab investigates the functions of the RNAs made during the latent state and if they contribute to gene silencing. What are the triggers of reactivation? Can these be targeted to prevent virus reactivation and shingles? To study these topics, the lab developed a new cultured human neuron system that mimics the interactions of virus and nerve cells in dishes. For example, the lab tries removing the latent virus from neurons using CRSPR-cas9 systems.
The third VZV project aims to understand why the live virus VZV vaccine is attenuated for growth in human skin and neurons. The vaccine virus contains hundreds of genome changes compared to a wild-type virus, in different combinations and mixes. The lab studies these mutations a few at a time, using models of human skin to probe which vaccine mutations are important in blocking VZV growth in the skin. If we know the cause of attenuation, we could easily improve and make a safer vaccine than the current vaccine virus and stop the occasional problems some have with the current VZV vaccine.