Viral Pathogenesis Unit-as part of the Howe Lab
James Chodosh, M.D., MPH, David G. Cogan Professor of Ophthalmology in the field of Cornea and External Disease, Harvard Medical School
Our laboratory’s long-term goal is to develop new information-based therapies for ocular surface inflammation due to viral infections. We study the molecular pathogenesis of adenoviruses in corneal infection. Ongoing projects include studies on the role of keratocytes, the resident cells of the eye’s corneal stroma, in the chemokine-driven innate immune responses to viral infection of the cornea. Specifically, we study signal transduction events in response to infection with adenoviruses in cultured human keratocytes, living mice, and complex tissue culture reconstructions of the human cornea, at the nucleic acid, protein, and cellular levels, and how those signaling events influence the expression of pro-inflammatory mediators. We also study how previously uncharacterized regions of the adenoviral genome contribute to viral pathogenesis. This work involves whole genome sequencing, bioinformatics, and proteomics, and use of a novel mouse model of corneal adenovirus infection.
1. Chodosh J, Astley RA, Butler MG, Kennedy RC. Adenovirus keratitis: a role for interleukin-8. Invest Ophthalmol Vis Sci 2000;41:783-789.
2. Natarajan K, Ghalayini AJ, Sterling RS, Holbrook RM, Kennedy RC, Chodosh J. Activation of focal adhesion kinase in adenovirus-infected human corneal fibroblasts. Invest Ophthalmol Vis Sci 2002;43:2685-2690.
3. Natajaran K, Rajala M, Chodosh J. c-Src activation induces early IL-8 expression in adenovirus-infected human corneal fibroblasts. J Immunol 2003;170:6234-6243.
4. Xiao J, Chodosh J. JNK regulates MCP-1 expression by adenovirus type 19 infected human corneal fibroblasts. Invest Ophthalmol Vis Sci 2005;46:3777-3782.
5. Rajala MS, Rajala RVS, Astley RA, Butt AL, Chodosh J. Corneal cell survival in adenovirus type-19 infection requires phosphoinositide-3-kinase/Akt activation. J Virol 2005;79:12322-12341.
6. Rajala MS, Rajala RVS, Astley RA, Butt AL, Chodosh J. Corneal cell survival in adenovirus type-19 infection requires phosphoinositide-3-kinase/Akt activation. J Virol 2005;79:12322-12341.
7. Chodosh J. Human adenovirus type 37 and the Balb/c mouse: progress towards a restricted adenovirus keratitis model. (American Ophthalmological Society Thesis). Trans Am Ophthalmol Soc 2006;104:338-357.
8. Chintakuntlawar AV, Astley RA, Chodosh J. Adenovirus type 37 keratitis in the C57BL/6J mouse. Invest Ophthalmol Vis Sci 2007;48:781-788.
9. Rajaiya J, Xiao J, Rajala RVS, Chodosh J. Human adenovirus type 19 infection of corneal cells induces p38 MAPK-dependent interleukin-8 expression. Virol J 2008;5:17. (doi:10.1186/1743-422X-5-17)
10. Robinson CM, Shariati F, Gillaspy AF, Dyer, DW, Chodosh J. Genomic and bioinformatics analysis of HAdV-37: new insights into corneal tropism. BMC Genomics. 2008;9:213.
11. Robinson CM, Rajaiya J, Walsh MP, Seto D, Dyer DW, Jones MS, Chodosh J. Computational analysis of human adenovirus type 22 provides evidence for recombination between human adenoviruses species D in the penton base gene. J Virol 2009;83;8980-5.
12. Chintakuntlawar AV, Zhou X, Rajaiya J, Chodosh J. Viral capsid is a pathogen-associated molecular pattern in adenovirus keratitis. PLoS Pathogens 2010;6;e1000841.
13. Robinson CM, Singh G, Henquell C, Walsh MP, Peigue-Lafeuille H, Seto D, Jones MS, Dyer DW, Chodosh J. Computational analysis and identification of an emergent human adenovirus pathogen implicated in a respiratory fatality. Virology 2011;409;141-7.