Paul R. (Kip) Kinchington, PhD
- Professor, Department of Ophthalmology
- Professor, Department of Microbiology and Molecular Genetics
- Member, Fox Center for Vision Restoration
- Member, Clinical and Translational Science Institute (CTSI)
Education & Training
- PhD in Microbiology and Virology, University of Leeds, England (UK)
- BSc (Hons) in Microbiology, University of Leeds, England (UK)
Dr. Kinchington’s research addresses molecular biology of human herpesviruses that cause vision loss and blindness. Most of the lab works on Varicella zoster virus (VZV), which causes chickenpox upon primary infection, and Herpes zoster (“Shingles”) when the virus reactivates from neuronal latency. We know little of the latent state in neurons. Zoster is also frequently complicated by debilitating, difficult-to-treat pain through unclear mechanisms. Despite VZV vaccines being available, zoster occurs in many as they age or become immune impaired.
The lab studies how VZV interacts with the infected cell, particularly human neurons. We are using a cultured human neuron system derived from embryonic stem cells, often in a channeled microfluidics culture platform that separates neuron soma and axons. This model was the first to enable visualization of fluorescent VZV capsids moving in axons and was the first system in which a VZV model of the latent state could be established that could be experimentally reactivated. Cultured neurons are used with recombinant VZV mutants to understand the “round trip” process of axonal transport, latency, reactivation and returned axonal transport to the periphery: and the role of a latency-associated RNA termed VLT. A second model is to investigate exploit rats to study the chronic pain that frequently follows Zoster. VZV in rats at the footpad or face induces mechanical hypersensitivity and pain lasting weeks. The rat model is being used with conditional replicating recombinant VZV to identify requirements for inducing pain: and use of gene delivery approaches to treat VZV pain.
Treat BR, Bidula SM, St Leger AJ, Hendricks RL and Kinchington PR. 2020. Herpes Simplex Virus 1-Specific CD8(+) T Cell Priming and Latent Ganglionic Retention Are Shaped by Viral Epitope Promoter Kinetics. J Virol. 94: pii: e01193-19. doi: 10.1128/JVI.01193-19.
Golani-Zaidie L, Borodianskiy-Shteinberg T, Bisht P, Das B, Kinchington PR and Goldstein RS. 2019. Bioinformatically-predicted varicella zoster virus small non-coding RNAs are expressed in lytically-infected epithelial cells and neurons. Virus Res. 274:197773. doi: 10.1016/j.viruses.2019.197773.
Laemmle L, Goldstein RS and Kinchington PR. 2019. Modeling Varicella Zoster Virus Persistence and Reactivation - Closer to Resolving a Perplexing Persistent State. Front Microbiol. 10:1634. doi: 10.3389/fmicb.2019.01634.
Kramer PR, Stinson C, Umorin M, Deng M, Rao M, Bellinger LL, Yee MB and Kinchington PR. 2017. Lateral thalamic control of nociceptive response after whisker pad injection of varicella zoster virus. Neuroscience. 356: 207-216.
Treat BR, Bidula SM, Ramachandran S, St Leger AJ, Hendricks RL and Kinchington PR. 2017. Influence of an immunodominant herpes simplex virus type 1 CD8+ T cell epitope on the target hierarchy and function of subdominant CD8+ T cells. PLoS Pathog. 13: e1006732.