What We Investigate
The overall goal of our laboratory is to obtain new insights into the host-virus interaction, particularly in HIV infection, and translate discoveries in molecular biology and virology to the clinic to aid in the treatment of HIV infection.
A subpopulation of HIV-infected lymphocytes is able to avoid viral or immune cytolysis and return to the resting state. While this latent reservoir of HIV infection is a significant clinical problem, the molecular mechanisms that underlie it are enigmatic.
Current lab work focuses on the molecular mechanisms that control the latent reservoir of HIV infection within resting T cells. We have found that cellular transcription factors widely distributed in lymphocytes can remodel chromatin and maintain quiescence of the HIV genome in resting CD4+ lymphocytes. This approach has been extended through bench studies to a clinical experiment demonstrating depletion of the latent reservoir of HIV infection in HIV+ patients [Lehrman 2005].
These studies give insight into the basic molecular mechanisms of eukaryotic gene expression, as well as new therapeutic approaches for HIV infection. Novel histone deacetylase inhibitors and their effects on viral chromatin and gene expression, and host genes, are under study. Other studies in the laboratory examine persistent HIV infection in other cell populations, and studies of HIV-induced lymphocyte apoptosis, likely a major mechanism through which HIV infection leads to immunodeficiency.