ROUTES, John, MD       Allergy and Clinical Immunology      NJMRC Goodman Building K613      303-398-1291      routesj@njc.org

RESEARCH INTERESTS:

• Immunobiology of Small DNA Tumor Viruses (Adenoviruses, Human papillomaviruses, SV40
• Cell Signalling Abnormalities in Common Variable Immunodeficiency

• Primary Immunodeficiencies (Adults)
• Asthma and Atopic Diseases

RECENT REPRESENTATIVE RESEARCH PUBLICATIONS:

• Routes JM, Colton LA, Ryan S, and Klemm DJ. CREB and C/EBP-alpha are Required for the "Superstimulation" of PEPCK Gene Transcription by Adenoviral E1A and Cyclic-AMP. Biochem. J. 2000;352:335-342

• Routes JM, Ryan S, Steinke J, Cook JL. Dissimilar immunogenicities of the the adnovirus E1A and human papillomavirus E7 proteins influence tumor development Virology 2000;277:48-57

• Routes JM, Ryan S, Clase A, Miura T, Kuhl A, Potter T, and Cook J. E1A Oncogene Expression in Tumor Cells Enhances Killing by TNF-Related Apoptosis Inducing Ligand (TRAIL) J. Immunol. 2000:165:4522-4527

• Routes JM, Nelson HS, Noda JA, and Simon FT. Lack of correlation between Chlamydia pneumoniae titers and adult onset asthma. J Allergy Clin Immunol. 105:391-2, 2000

• Associate Editor: The Year Book of Allergy, Asthma and Clinical Immunology (Mosby)

Human papillomaviruses (HPV) cause common skin warts. Until recently, it was thought that the only consequence of HPV-genital tract infections were benign genital warts. However, recent studies indicate that HPVs cause over 90% of cervical carcinomas. Worldwide, cervical cancer appears to be the most frequent female malignancy accounting for approximately 24% of all cancers in women. Recent research has helped define the molecular basis by which HPVs cause cervical cancer. In a few of the HPV-infected cells, a small part of the viral genome actually integrates into our chromosomal DNA. Following integration, the expression of two HPV genes called E7 and E6, can change (transform) a normal cell into a cancer cell. These cancer cells then somehow evade our immune response, grow and divide unchecked, and eventually form invasive cancers.

Another virus that commonly infects humans can also make cancer cells but doesn’t cause cancer. Human adenoviruses (Ad) are common pathogens causing self-limited respiratory tract infections. Ad also has a gene (E1A) that is strikingly similar to E7 gene of HPV and can also change normal cells into cancer cells. However, unlike cancer cells expressing the HPV E7 gene, cancer cells expressing the E1A gene are eliminated by our immune system. Therefore, Ad are unable to cause cancer in humans despite their capacity to change normal cells into cancer cells. Why two viruses, which contain cancer-causing genes that are so strikingly similar, should result in such different diseases (cancer versus benign respiratory tract infections) is an intriguing and significant question for immunology research.

My research compares our immune response against cancer cells caused by Ad with those caused by HPV. Our recent studies using mice show that their immune system is unable to eliminate cancer cells expressing the E7 protein whereas E1A-expressing tumor cells are rejected. We are now is focusing on the reasons why our immune system is so adept at eliminating tumor cells that express E1A but not E7.

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