Department of Biology Johns Hopkins University 3400 North Charles Street Baltimore, MD 21218-2685 U.S.A.

Office Telephone: Lab Telephone: Department Fax: Email:

410.516.6602 410.516.6602 410.516.5213 parowe@jhmi.edu

Office- Mudd 137A

RESEARCH INTERESTS

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Antiviral response to infectious pathogenes; Toll-like receptors; role of the family of IRF-factors, HIV-1, IRF and IFN receptor null mice - response to viral infection; oncogenesis

Our laboratory has been interested in the effects viral infection on the expression of cellular genes and in the novel approaches to modulation of the antiviral and anti-inflammatory responses. We have shown that three transcription factors of the interferon respective factors family (IRF-3,5 and 7) that are functioning as a direct inducer of virus mediated signaling in infected cells. These factors play a critical role in the induction of cytokine and chemokine genes. However, the unregulated production of cytokines and chemokines has been detected in autoimmune diseases.

The role of Interferon and IRF factors in response to viral and bacterial infections has been studied in mice from which either the Interferon receptor or IRF-5 were deleted. These mice serve also as excellent model system for the pathogen induced autimmune disease.

The role of innate antiviral response to HIV-1 infection has been analyzed.
We have shown recently that the interferon induced protein-ISG15 targets the cellular ubiquitination steps that are essentil for HIV-1 assembly and release of virions. Overexpression of ISG15 mimics the IFN effect and inhibits HIV-1 while it elimination reverses the IFN induced inhibition.
Thes data indicate that the antiviral response targets ubiquitination and suggest a novel approach to the antiviral therapy.

 

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REPRESENTATIVE PUBLICATIONS

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Redecke, V., Hacker, H., Datta, S.K., Fermin, A., Pitha, P.M., Broide, D.H., and Raz, E. Cutting edge: activation of Toll-like receptor 2 induces a Th2 immune response and promotes experimental asthma, J. Immunol. 172:2739-2743, 2004. Pub Med Reference

Barnes, B.J., Richard, J., Mancl, M., Hanash, S., Beretta, L., and Pitha, P.M. Global and distant targets of IRF-5 and IRF-7 during innate response to viral infection, J. Biol. Chem. 279:45194-45207, 2004. Pub Med Reference

Pitha, P.M. Unexpected similarities in cellular responses to bacterial and viral invasion, PNAS 101:695-696, 2005. Pub Med Reference

Schoenemeyer, A., Barnes, B.J., Mancl, M.E., Latz, E., Goutagny, N., Pitha, P.M., Fitzgerald, K.A., and Golenbock, D.T. The interferon regulatory factor, IRF5, is a central mediator of TLR7 signaling, J. Biol. Chem.
280:17005-17012, 2005. Pub Med Reference

Mancl, M.E., Hu, G., Sangster-Guity, N., Olshalsky, S.L., Hoops, K., Fitzgerald-Bocarsly, P., Pitha, P.M., Pinder, K., and Barnes, B.J. Two discrete promoters regulate the alternatively spliced human interferon regulatory factor-5 isoforms. J. Biol. Chem. 280:21078-21090, 2005. Pub Med Reference

Okumura, A., Lu, G., Pitha-Rowe, I. and Pitha, P.M. Innate antiviral response targets HIV-1 release by the induction of ubiquitin *like protein ISG15, PNAS 103:1440-1445, 2006. Pub Med Reference

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Lab Members

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Postdoctoral Fellows:
Mumtaz Yaseen
Jasmine Chun-Yang Lien