Virology Faculty Member - James Chodosh

James Chodosh

David G. Cogan Professor of Ophthalmology in the Field of Cornea and External Disease

Massachusetts Eye and Ear Infirmary
Howe Laboratory
243 Charles Street
Boston, MA 02114
Tel: 617-573-6398
Fax: 617-573-4324
Email: james_chodosh@meei.harvard.edu
Lab Members: 8 lab members



The mission of our laboratory is to elucidate the biology and evolution of human adenoviruses.

Virus induced signal transduction – Human adenoviruses are the etiologic agents of epidemic keratoconjunctivitis, a severe and highly transmissible infection of the eye. We have shown the primacy of Src, MAPK, and PI3K signaling in corneal infection by adenoviruses, and believe cell signaling represents fertile ground for development of novel therapeutics. We use primary cell culture, complex tissue culture reconstructions of the cornea, and transgenic and knockout mice to study the role of individual signaling molecules in adenovirus pathogenesis.

Innate immune responses to virus infection – We developed a mouse model of adenovirus keratitis, and used it to show that viral capsid was the major molecular pattern for innate immune responses in the cornea. Currently, we are investigating the specific roles of unique cell types present in the cornea in the early innate immune responses to viral infection. We want to elucidate the unique interactions between specific molecular patterns expressed by the adenovirus and individual corneal stromal and bone marrow derived cell phenotypes.

Adenovirus genomics and evolution – Concurrent with our interest in molecular patterns and innate immunity, we have turned our attention more closely to the adenovirus pathogen as a physical entity, and have completed whole genome sequencing of all the remaining unsequenced human adenoviral prototypes (no. = 20). This led to our confirmation of homologous recombination as a major mechanism for evolution of the virus. Our current focus is to understand the molecular basis for homologous recombination between human adenoviruses.









Last Update: 10/22/2013



Publications

Natajaran K, Rajala M, Chodosh J. c-Src activation induces early IL-8 expression in adenovirus-infected human corneal fibroblasts. J Immunol 2003;170:6234-43.

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;79:12322-41.

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.

Chintakuntlawar AV, Zhou X, Rajaiya J, Chodosh J. Viral capsid is a pathogen-associated molecular pattern in adenovirus keratitis. PLoS Pathogens 2010;6:e1000841.

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.

Rajaiya J, Yousuf MA, Singh G, Stanish H, Chodosh J. Heat shock protein 27 mediated signaling in viral infection. Biochemistry. 2012;51:5695-702.

Robinson CM, Zhou X, Rajaiya J, Yousuf MA, Singh G, Deserres JJ, Walsh MP, Wong S, Seto D, Dyer DW, Chodosh J, Jones MS. Predicting the next eye pathogen: analysis of a novel adenovirus. MBio. 2013;4. doi:pii: e00595-12. 10.1128/mBio.00595-12.

Robinson CM, Singh G, Lee JY, Dehghan S, Rajaiya J, Liu EB, Yousuf MA,
Betensky RA, Jones MS, Dyer DW, Seto D, Chodosh J. Molecular evolution of human adenoviruses. Sci Rep. 2013;3:1812. doi: 10.1038/srep01812.



© 2013 by the President and Fellows of Harvard College