BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Kinchington, Paul R.
Professor of Ophthalmology, Molecular
Microbiology and Genetics
eRA COMMONS USER NAME (credential, e.g., agency login)
kinchingtonp
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and
residency training if applicable.)
DEGREE
INSTITUTION AND LOCATION
MM/YY
FIELD OF STUDY
(if applicable)
Univ. of Leeds, Leeds, England
Univ. of Leeds, Leeds, England
B.Sc.
(honors)
Ph.D.
1979
Microbiology
1983
Microbiology
A; Personal Statement
The human neurotropic herpesviruses HSV and VZV cause many ocular infections and VZV induces a painful
morbid disease known as zoster. I have worked with these viruses for over 25 years, examining their
molecular biology and probing virus host cell interactions at the single cellular level and in animal models. Our
group identified several aspects of the basic biology and mechanisms of VZV growth including the roles and
functions of a viral protein kinase that is required for growth in tissues of the eye.
My research programs now address models of human herpesvirus disease and virus interactions with the
neuron. The first addresses a rat model of VZV induced ganglionic pain, and seeks to derive new treatment
strategies to prevent chronic pain as a potential for PHN treatment. This project also seeks to identify VZV
mutants that are unable to cause pain, and also address the mechanism by which VZV causes prolonged pain
indicators in the rat. Secondly, We have developed a human neuronal system in vitro from hESC cells to
examine VZV-neuron interactions in collaboration with Dr Ron Goldstein. We have now established the
feasibility of a human neuron system to address VZV axonal transport, infection of neurons, neuronal spread
and the VZV persistent state, areas that remain very unclear or completely unexplored. Third, we are using
the murine model of HSV-1 corneal infection and latency to address the goal of enhancing the CD8 T cell
infiltrate on the latently infected ganglia that can prevent reactivation and ocular disease
B. Positions and honors
Positions
1983-1986
Post-Doctoral Research Associate, Dept. of Biochemistry, Uniformed Services Univ. of the
Health Sciences USUHS), Bethesda, MD
1986-1990
Research Instructor, Biochemistry, USUHS
1991-1996
Assistant Professor, Dept. of Ophthalmology, University of Pittsburgh School of Medicine,
Pittsburgh, PA
1992-1996
Assistant Professor (Secondary Appointment), Dept. of Molecular Genetics & Biochemistry,
University of Pittsburgh School of Medicine, Pittsburgh, PA
1996-2012
Associate Professor, Depts. of Ophthalmology and Molecular Microbiology and Genetics,
University of Pittsburgh School of Medicine, Pittsburgh, PA
2011-curr
Professor, Depts. of Ophthalmology and Molecular Microbiology and Genetics, University of
Pittsburgh School of Medicine, Pittsburgh, PA
Honors
1994
March of Dimes Basil O’Connor Scholar Award
1999
Research to Prevent Blindness Lew Wasserman Award
2004
MERCK Expert panel member to evaluate Varicella vaccine on Herpes Zoster
2007
University of Pittsburgh School of Medicine Graduate program “Most Outstanding Mentor” award
2008
VZV Research Foundation “Senior Fellow” award for Outstanding Scientific Achievement
2012-2017 Elected to full membership, University of Pittsburgh “Academy of Master Educators”
Review/study sections
2002-curr VZV Research Foundation Scientific Advisory board
2005-curr Journal of Virology, Editorial board.
2008-curr Virus Research, Editorial board
2009-curr J. Clinical Virology Editorial board
2009-curr Herpesviridae, Editorial board
2006-curr “Fight for Sight” Study section
2003, 2004, NIH CSR“Experimental Virology” Study section
2009
NIH Special Emphasis Panel CSR ARRA Ocular Immunology.
2011 Lousianna Regents Board grant reveiw
2009 Oct; 2011 Jan, June: NIH CSR ‘Virology B’ Study Section
2010 Jan, Oct
NIH CSR ZRG1 IDM-P study section
Full member June 2012-2017 NIH CSR ‘Virology B’ Study Section
C. Selected Publications
Grigoryan S, Kinchington PR, Yang IH, Selariu A, Zhu H, Yee M, Goldstein RS.Retrograde axonal transport
of VZV: kinetic studies in hESC-derived neurons. JNeurovirol. 2012 Aug 24. PubMed PMID: 22918852.
Kinchington PR, St Leger AJ, Guedon JM, Hendricks RL. Herpes simplex virus and varicella zoster virus, the
house guests who never leave. Herpesviridae. 2012 Jun 12;3(1):5. PubMed PMID: 22691604.
Dukhovny A, Sloutskin A, Markus A, Yee MB, Kinchington PR, Goldstein RS. Varicella-zoster virus infects
human embryonic stem cell-derived neurons and neurospheres but not pluripotent embryonic stem cells or
early progenitors. J Virol. 2012 Mar;86(6):3211-8. PMID: 22238301; PubMed Central PMCID: PMC3302301.
Kinchington PR, Goins WF. Varicella zoster virus-induced pain and post-herpetic neuralgia in the human host
and in rodent animal models. J Neurovirol. 2011 17(6):590-9. PMID: 22205584.
Markus A, Grigoryan S, Sloutskin A, Yee MB, Zhu H, Yang IH, Thakor NV, Sarid R, Kinchington PR*,
Goldstein RS* (*= co-corresponding/lead authors). Varicella-zoster virus (VZV) infection of neurons derived
from human embryonic stem cells: direct demonstration of axonal infection, transport of VZV, and productive
neuronal infection. J Virol. 2011 Jul;85(13):6220-33. PMCID: PMC3126485.
Erazo A, Yee MB, Banfield BW, Kinchington PR. The alphaherpesvirus US3/ORF66 protein kinases direct
phosphorylation of the nuclear matrix protein matrin 3. J Virol. 2011 Jan;85(1):568-81. PMCID: PMC3014177.
Erazo A, Yee MB, Osterrieder N, Kinchington PR. Varicella-zoster virus open reading frame 66 protein kinase
is required for efficient viral growth in primary human corneal stromal fibroblast cells. J Virol. 2008
Aug;82(15):7653-65. PMCID: PMC2493351.
Eisfeld AJ, Yee MB, Erazo A, Abendroth A, Kinchington PR. Downregulation of class I major
histocompatibility complex surface expression by varicella-zoster virus involves open reading frame 66 protein
kinase-dependent and –independent mechanisms. J Virol. 2007 Sep;81(17):9034-49. PMCID: PMC1951447.
Sloan E, Henriquez R, Kinchington PR, Slobedman B, Abendroth A. Varicella-zoster virus inhibition of the
NF-κB pathway during infection of human dendritic cells: role for open reading frame 61 as a modulator of NFκB activity. J Virol. 2012 Jan;86(2):1193-202. PubMed Central PMCID: PMC3255823.
Bertke AS, Swanson SM, Chen J, Imai Y, Kinchington PR, Margolis TP.A5-positive primary sensory neurons
are nonpermissive for productive infection with herpes simplex virus 1 in vitro. J Virol. 2011 Jul;85(13):6669-77.
PubMed Central PMCID: PMC3126511.
Verweij MC, Lipinska AD, Koppers-Lalic D, van Leeuwen WF, Cohen JI, Kinchington PR, Messaoudi I,
Bienkowska-Szewczyk K, Ressing ME, Rijsewijk FA, Wiertz EJ. The capacity of UL49.5 proteins to inhibit TAP
is widely distributed among members of the genus Varicellovirus. J Virol. 2011 Mar;85(5):2351-63.
PubMed Central PMCID: PMC3067808.
Walters MS, Kinchington PR, Banfield BW, Silverstein S. Hyperphosphorylation of histone deacetylase 2 by
alphaherpesvirus US3 kinases. J Virol. 2010 Oct;84(19):9666-76.; PubMed Central PMCID: PMC2937806.
Ramachandran S, Davoli KA, Yee MB, Hendricks RL, Kinchington PR. Delaying the expression of herpes
simplex virus type 1 glycoprotein B (gB) to a true late gene alters neurovirulence and inhibits the gB-CD8+ Tcell response in the trigeminal ganglion. J Virol. 2010 Sep;84(17):8811-20. PMCID: PMC2919033.
Abendroth A, Kinchington PR, Slobedman B. Varicella zoster virus immune evasion strategies. Curr Top
Microbiol Immunol. 2010;342:155-71. Review. PubMed PMID: 20563710.
Walters MS, Erazo A, Kinchington PR, Silverstein S. Histone deacetylases 1 and 2 are phosphorylated at
novel sites during varicella-zoster virus infection. J Virol. 2009 Nov;83(22):11502-13. Epub 2009 Sep 9.
PubMed PMID: 19740981; PubMed Central PMCID: PMC2772673.
Knickelbein JE, Khanna KM, Yee MB, Baty CJ, Kinchington PR, Hendricks RL. Noncytotoxic lytic granulemediated CD8+ T cell inhibition of HSV-1 reactivation from neuronal latency. Science. 2008 Oct
10;322(5899):268-71. PubMed PMID: 18845757; PubMed Central PMCID: PMC2680315.
Leisenfelder SA, Kinchington PR, Moffat JF. Cyclin-dependent kinase 1/cyclin B1 phosphorylates varicellazoster virus IE62 and is incorporated into virions. J Virol. 2008 Dec;82(24):12116-25. Epub 2008 Sep 17.
PubMed PMID: 18799590; PubMed Central PMCID: PMC2593305.
Ramachandran S, Knickelbein JE, Ferko C, Hendricks RL, Kinchington PR.Development and pathogenic
evaluation of recombinant herpes simplex virus type 1 expressing two fluorescent reporter genes from different
lytic promoters. Virology. 2008 Sep 1;378(2):254-64. Epub 2008 Jul 11. PMCID: PMC2613845.
Milikan JC, Kinchington PR, Baarsma GS, Kuijpers RW, Osterhaus AD, Verjans GM. Identification of viral
antigens recognized by ocular infiltrating T cells from patients with varicella zoster virus-induced uveitis. Invest
Ophthalmol Vis Sci. 2007 Aug;48(8):3689-97. PubMed PMID: 17652740.
Ramachandran S, Kinchington PR. Potential prophylactic and therapeutic vaccines for HSV infections. Curr
Pharm Des. 2007;13(19):1965-73. Review. PubMed PMID: 17627530.
Verjans GM, Hintzen RQ, van Dun JM, Poot A, Milikan JC, Laman JD, Langerak AW, Kinchington PR,
Osterhaus AD. Selective retention of herpes simplex virus-specific T cells in latently infected human trigeminal
ganglia. Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3496-501. PMCID: PMC1805572.
Hasnie FS, Breuer J, Parker S, Wallace V, Blackbeard J, Lever I, Kinchington PR, Dickenson AH, Pheby T,
Rice AS. Further characterization of a rat model of varicella zoster virus-associated pain: Relationship between
mechanical hypersensitivity and anxiety-related behavior, and the influence of analgesic drugs. Neuroscience.
2007 Feb 23;144(4):1495-508 PMCID: PMC2394505.
Kowalski RP, Thompson PP, Kinchington PR, Gordon YJ. Evaluation of the SmartCycler II system for realtime detection of viruses and Chlamydia from ocular specimens. Arch Ophthalmol. 2006 Aug;124(8):1135-9.
PubMed PMID: 16908816.
Eisfeld AJ, Turse SE, Jackson SA, Lerner EC, Kinchington PR. Phosphorylation of the varicella-zoster virus
(VZV) major transcriptional regulatory protein IE62 by the VZV open reading frame 66 protein kinase. J Virol.
2006 Feb;80(4):1710-23. PubMed PMID: 16439528; PubMed Central PMCID: PMC1367140.
Hood C, Cunningham AL, Slobedman B, Arvin AM, Sommer MH, Kinchington PR, Abendroth A. Varicellazoster virus ORF63 inhibits apoptosis of primary human neurons. J Virol. 2006 Jan;80(2):1025-31. PMCID:
PMC1346839.
Garry EM, Delaney A, Anderson HA, Sirinathsinghji EC, Clapp RH, Martin WJ,Kinchington PR, Krah DL,
Abbadie C, Fleetwood-Walker SM. Varicella zoster virus induces neuropathic changes in rat dorsal root
ganglia and behavioral reflex sensitisation that is attenuated by gabapentin or sodium channel blocking drugs.
Pain. 2005 Nov;118(1-2):97-111. Epub 2005 Oct 5. PubMed PMID: 16213091.
Decman V, Freeman ML, Kinchington PR, Hendricks RL. Immune control of HSV-1latency. Viral Immunol.
2005;18(3):466-73. Review. PubMed PMID: 16212525.
Biswas PS, Banerjee K, Kim B, Kinchington PR, Rouse BT. Role of inflammatory cytokine-induced
cyclooxygenase 2 in the ocular immunopathologic disease herpetic stromal keratitis. J Virol. 2005
Aug;79(16):10589-600. Erratum in: J Virol. 2005 Dec;79(24):15590. PMCID: PMC1182687.
Decman V, Kinchington PR, Harvey SA, Hendricks RL. Gamma interferon can block herpes simplex virus
type 1 reactivation from latency, even in the presence of late gene expression. J Virol. 2005 Aug;79(16):1033947. PMCID: PMC1182646.
Biswas PS, Banerjee K, Kinchington PR, Rouse BT. Involvement of IL-6 in the paracrine production of VEGF
in ocular HSV-1 infection. Exp Eye Res. 2006 Jan;82(1):46-54. Epub 2005 Jul 11. PubMed PMID: 16009363.
Kinchington PR, Romanowski EG, Jerold Gordon Y. Prospects for adenovirus antivirals. J Antimicrob
Chemother. 2005 Apr;55(4):424-9. Epub 2005 Mar 2. Review. PubMed PMID: 15743895.
D: ONGOING RESEARCH SUPPORT
RO1 NS064022 KINCHINGTON, PR (PI) 01/15/09-12/31/13
NIH /NINDS
Varicella zoster virus-Induced Pain in a Rat Model of Post-Herpetic Neuralgia.
To assess the VZV genes and proteins expressed during the pain phase in rats innoculated with VZV: to
mutate VZV genes to attenuate the VZV induced pain response; to determine if expression of single VZV
genes induces the pain response; To treat VZV induced pain using HSV vectors that alter the inhibitory tone of
pain or modulate inflammation processes.
RO1 EY015291 Kinchington (PI)
7/01/09-6/30/14 NIH/NEI
Gene expression in HSV-1 latency after corneal infection“
Specific aim 1 will determine the importance of proteins made after the onset of viral DNA replication as targets
for the cellular immune response that blocks reactivation. Specific aim 2 will test the efficacy of a epitope
transgene in inducing a protective cellular immune response that blocks reactivation. Specific Aim 3 will identify
the viral targets of reactivation blocking Cellular immune response in the absence of an immunodominant
epitope.
P30 EY08098 (R. Hendricks PI) 04/01/89-03/31/13
NIH/NEI
“Core Grant For Vision Research”
The Core Grant will provide support for the following centralized research modules: Hybridoma/Tissue Culture,
Molecular Biology, Electronic Shop, and Morphology Module.
Role Co-I (Module Director, Molecular Biology)
R01 EY005945 (Hendricks, PI) 1/1/04-12/31/13 NIH/NEI
Cytotoxic Lymphocytes and HSV-1 Corneal Lesions
This project aims to understand the role of immune cells in the development of ocular infections and corneal
disease
Role Co-I
R01 EY09368 (J. Funderburgh, PI) 4/1/08-3/31/13
NIH/NEI
Proteoglycans in normal and scarred corneas
This project seeks to determine the expression patterns of genes involved in the synthesis and expression
of glycosaminoglycans, with the goal to determining how they contribute to normal corneal development and to
diseases of the cornea.
Role Co-I
Pending support
NS R21 182662 (Kinchington, P.R. PI) (scored 1st percentile)
A new in vitro nueron model of axonal transport and persistence of VZV NIH NINDS
This proposal aims to develop peripheral neurons from hESC and IPS and use then to evaluate transport and
latency of human alphaherpesviruses, particularly VZV