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Member Information
Jeffrey Bergelson, MD
Assistant Professor, Departments of Pediatrics and Microbiology
Office Phone: 215 590-3771
Office Fax: 215 590-2025
Email: bergelson@email.chop.edu
Website(s): http://www.med.upenn.edu/camb/faculty/mv/bergelson.html
Education: MD 1981, University of Pennsylvania
Keywords: Virus Entry, Adenovirus, Coxsackievirus, Viral Pathogenesis, Virus Receptor, Vaccine Delivery
Research and/or Clinical Interests:
Virology, cell biology; virus receptors, virus tropism; vaccine vectors and identifying the cellular functions/virus receptors and their role in virus tropism; developing adenovirus vectors for AIDS vaccination.
Summary:
My laboratory has been interested in function of cell surface receptors as determinants of tissue tropism. For the last several years our research has focused on the coxsackievirus and adenovirus receptor (CAR) a transmembrane protein that mediates attachment and infection caused by these unrelated viruses. Since we first identified CAR several years ago, work in our laboratory and many others has demonstrated its central role in cell and tissue susceptibility to adenovirus-mediated gene delivery, as well as to in the pathogenesis of viral infections.
We are also interested in this molecule's physiologic functions, independent of its function as a virus receptor. CAR mediates homotypic cell-cell recognition, and is a functional component of the epithelial tight junction. CAR-mediated cell adhesion appears to regulate cell growth, and CAR appears to play an essential function during embryonic development.
An additional interest in the lab is the development of adenovirus vectors for use in AIDS immunization. Because many potential vaccine recipients have encountered adenoviruses in the past, they have produced serotype-specific neutralizing antibodies that interfere with vaccine efficacy. We are working to modify the hexon protein, the major site of serotype-specific neutralization, in order to generate vectors that resist neutralization by pre-existing antibodies.
Representative Publications:
Bergelson JM, Shepley MP, Chan BMC, Hemler ME, Finberg RW. Identification of the integrin VLA-2 as a receptor for echovirus 1. Science. 1992;255: 1718-1720.
Bergelson JM, Chan M, Solomon K, St. John NF, Lin H, Finberg RW. Decay-accelerating factor (CD55), a glycosylphosphatidylinositol-anchored complement regulatory protein, is a receptor for several echoviruses. Proc. Natl. Acad. Sci. USA 1994;91:6245-6248.
Bergelson JM, Cunningham JA, Droguett G, Kurt-Jones EA, Krikthivas A, Hong JS, Horwitz MS, Crowell RL, Finberg RW. Isolation of a common receptor for coxsackie B viruses and adenoviruses 2 and 5. Science 1997; 275: 1320-1323.
Pickles RJ, Fahrner J, Petrella J, Boucher RC, Bergelson JM. Retargeting the coxsackievirus and adenovirus receptor to the apical surface of polarized epithelial cells reveals the glycocalyx as a barrier to adenovirus-mediated gene transfer. J. Virology 2000, 74: 6050-6057.
Cohen CJ, Shieh JT-C, Pickles RJ, T Okegawa T, Hsieh J-T, Bergelson JM. The coxsackievirus and adenovirus receptor (CAR) is a transmembrane component of the tight junction. Proc. Natl. Acad. Sci. USA 2001, 98:15192-15196.
Cohen CJ, Gaetz J, Ohman T, Bergelson JM. Multiple regions within the coxsackievirus and adenovirus receptor cytoplasmic domain are required for basolateral sorting. J. Biol. Chem. 2001, 276:25392-25398.
Xiang Z-Q, Gao G, Reryes-Sandoval A, Cohen CJ, Li Y, Bergelson JM, Wilson JM, Ertl HCJ. Novel, chimpanzee serotype 68-based adenoviral vaccine carrier for induction of antibodies to a transgene product. J Virol. 2002, 76: 2667-2675.
Cohen CJ, Xiang ZQ, Gao G-P, Ertl HCJ, Wilson JM, Bergelson JM. Chimpanzee adenovirus CV68 adapted as a gene delivery vector interacts with the coxsackievirus and adenovirus receptor (CAR). J. Gen. Virol. 2002; 83: 151-155.
Shieh JT, Bergelson JM. Interaction with decay accelerating factor (DAF) facilitates coxsackievirus B infection of polarized epithelial cells. J. Virol. 2002, 76: 9474-9480.
