Integration of the retroviral genome into a host chromosome is an essential part of the HIV life cycle. However, understanding of integration is still incomplete. Our studies of host DNA repair factors have identified both positive and negative regulators of retroviral infection. Proteins of the nucleotide excision repair pathway, XPB and XPD, are able to defend the host genome from retroviral integration by degrading the viral cDNA by an evolutionarily ancient mechanism. In contrast, base excision repair (BER) proteins enhance HIV integration. We are continuing to explore the role of BER proteins during integration. Finally, we are evaluating the role of chromatin during integration. Integrase favors DNA wrapped around nucleosomes far more than naked DNA. These studies provide fundamental knowledge of integration that may be useful for enhancing anti-retroviral therapy and also for targeting integration of retroviral gene therapy vectors.
Education and Training
PhD, Biology, University of California, San Diego, 2000
BS, Biology, Massachusetts Institute of Technology, 1993
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