Research Interests Our research focuses on two herpesviruses which have major implications for eye disease: Varicella Zoster Virus (VZV) which causes chickenpox (varicella) and Shingles (also known as herpes zoster) which can infect and cause pain in the eye and Herpes Simplex Virus Type 1 which causes recurrent corneal disease that reduces visual acuity and may lead to blindness. REGARDING VZV: The thrust of the laboratory is to understand how viral encoded proteins control and regulate viral and host gene expression and viral assembly during lytic infection. We study the functions and cooperative interactions of the transcriptional regulatory proteins, the tegument proteins and, more recently, the co-operation of these with two viral protein kinases. One area we are actively investigating is how a viral kinase regulates the nuclear import of a key transcriptional regulatory protein, switching its functions from regulatory DNA binding and transcriptional roles early in infection to cytoplasmic, virion assembly functions late in infection. We are also investigating the ability of this kinase and other VZV tegument proteins to regulate the surface presentation of MCH-1 antigen presentation on the infected cell surface. A third direction has narrowed on to how this kinase affects the host cell cytoskeletal structure and also its resistance to apoptosis. REGARDING HSV: We are developing and using two color fluorescent viruses to track the regulation of gene expression at the single cell level in latently infected neurons of mice infected with HSV-1. It is intended to identify those viral antigens expressed during abortive reactivation, and to design vaccines to those antigens which act specifically at the level of inducing cellular immunity at the site of latency. The lab also carries out studies in conjunction with Dr. Jerold Gordon that are aimed at identifying suitable candidate antivirals for the treatment of adenovirus ocular infections. This includes the subsequent derivation and molecular characterization of resistance to those antivirals.   Selected Publications Erazo A, Yee MB, Osterrieder N, Kinchington PR. Varicella-zoster virus (VZV) open reading frame 66 protein kinase is required for efficient viral growth in primary human corneal stromal fibroblast cells. J Virol. 2008 May 21. 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. Ramachandran S, Kinchington PR. Potential prophylactic and therapeutic vaccines for HSV infections.Curr Pharm Des. 2007;13(19):1965-73. 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. 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. >Complete Publication Listing   Grant Support NIH: Gene expression in HSV-1 latency after corneal infection. Role: Principal Investigator NIH/NEI: Core grant for vision research. Role: Co-Investigator NEI R01: Varicella Zoster virus regulatory proteins. Role: Principal Investigator NIH/NEI R01: Proteoglycans in normal and scarred corneas. Role: Co-Investigator NEI R01: Experimental pathogenesis & therapy of ocular adenovirus Role: Co-Investigator   Other Links The VZV Research Foundation Dept. of Ophthalmology University of Pittsburgh

Paul R. (Kip) Kinchington, Ph.D., Associate Professor of Ophthalmology Office:  1016 EEI Lab: 1014 and 1020 EEI Phone: 412 647 6319 Fax: 412 647 5880 kinch@.upmc.edu   Academic Affiliations Department of Ophthalmology Department of Microbiology and Molecular Genetics   Education 1979 - B.Sc. Microbiology (Honors) University of Leeds, England 1983 - Ph.D. Microbiology University of Leeds, England (Thesis title: Studies of herpes simplex virus glycoproteins and antigenic sites involved in neutralization) 1983-1986 - Post-doc. Uniformed Services University of the Health Sciences Bethedsa, MD.   Lab Personnel MVM Graduate Students: Angie Erazo, Svridya Ramachandran Research Technician: Katherine Davoli Research Associates: Michael Yee (Lab Manager): J-P. Vergnes