Area of Interest
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 chronic viral diseases. We seek a better understanding of the interactions between HIV and the host cell on the molecular level, with an eye to use these insights to improve the treatment of HIV infection, and the management of the HIV pandemic. Current work focuses on the molecular mechanisms that control the latent reservoir of HIV infection within resting T cells.
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. We have found that YY1 and LSF, cellular transcription factors widely distributed in lymphocytes, can repress HIV-1 gene activity and decrease the production of HIV-1 by infected cells. My laboratory has found that YY1 and LSF repress HIV-1 via chromatin remodeling, and we are examining the factors that direct and regulate this process.
We have described two distinct and specific mechanisms to recruit the chromatin remodeling enzyme, histone deacetylase 1, to the proviral promoter. The laboratory is attempting to further unravel the precise molecular events that underlie HIV latency, and simultaneously test novel reagents that perturb latency in T cells obtained from HIV+ patients. These studies are being followed by clinical experiments that attempt to deplete the latent reservoir of HIV infection in small, proof-of-concept studies in HIV+ volunteers.
These efforts have led us into translational approaches to persistent HIV infection that are more and more similar to oncological approaches to tumor therapy than traditional infectious disease approaches to infections. As we study host systems that regulate persistent HIV genomes, they are similar to those that studied in oncogenesis. We study and test novel HDAC inhibitors that are also in use or in development in cancer chemotherapy. An association with the LCC would clearly offer intellectual benefit to our work, and it is possible that our work or findings would stimulate novel approaches in the cancer community as well. Certainly approaches to chronic lentiviral infection would be of interest to LCC scientists studying chronic herpesvirus infections, as many of the host regulatory system are overlapping.
Awards and Honors
IDSA young investigator, 1997
Fellow, Infectious Dis. Society of America, 2000
Magna Cum Laude, Harvard College, 1981
Clinical Associates award, Am. Coll. Phys., 1988
NIH Physician-Scientist award (K-11), 1991-94
Fellow, American College of Physicians, 1996
amfAR Basic Science award, 2001
Am. Society for Clinical Investigation, 2005
Editorial Board, AIDS (2006-)
Editorial Board, J Virology (2008-)
Nat'l Found. Infect. Dis. young investigator, 1996