345 E. 24th St, room 921A
I received my PhD from the University of Pennsylvania in immunology in 1994. After post-doctoral training at the University of Alabama at Birmingham, I was appointed to a faculty position at the New York University College of Dentistry in 2006.
My laboratory studies the replication, pathogenesis and immunology of the human immunodeficiency virus (HIV). In prior years I have pioneered the study of HIV-1 replication in resting CD4 T cells, epigenetic regulation of latency, recombination and single cell analysis of HIV-1 replication dynamics. HIV-1 replication in resting CD4 T cells, latency, Vpr and viral dynamics are current interlocking interests of my laboratory. Resting CD4 T cells represent early important targets of infection and they carry the largest known latent viral reservoir. Vpr, latency and unintegrated genomes all intersect with resting CD4 T cells in ways my laboratory is now uncovering.
Bringing these topics together is the epigenetic regulation of HIV-1 replication. Once the HIV-1 RNA genome is delivered into a cell, it undergoes conversion to a DNA copy by the process of reverse transcription. The viral DNA is then integrated into the cell’s nuclear DNA, thus enabling the virus to persist for the life span of the cell. In order for RNA transcription to occur, the viral DNA must be associated with nucleosomes, complexes of histone proteins that the DNA wraps. The study of HIV-1 gene expression and latency has focused extensively on understanding these nucleosomes and the post-translational modifications of their histones that regulate transcription. However, when and how nucleosomes are initially installed on the viral DNA, and which cellular and viral factors influence these early events is not well understood. My laboratory is studying these processes funded by a 5 year NIH/NIAID R01 grant.
We are also studying the influence of HIV-1 transmission modalities to viral replication dynamics. This project is funded by the NSF through 2020. RNA viruses are characterized by a high mutation rate, allowing them to rapidly diversify and readily adapt to environmental challenges, which makes them a near-ideal model system to test evolutionary and selection theories that are difficult to approach in more complex organisms. Typically, virus genomes are considered as isolated entities, however, multiple infection (coinfection) of cells is a common occurrence. Coinfection results in a series of poorly understood social interactions, which have the power to shape evolutionary trajectories. For example, genetically divergent viruses of the same species can help or inhibit each other, and they can exchange genetic material. HIV-1 represents a highly tractable experimental system for this purpose. HIV-1 multiple infection is promoted by cell-to-cell contact and the formation of virological synapses, where multiple viruses are simultaneously transferred from one cell to another. In contrast, spread via the release of free virus particles promotes single infection. The relative occurrence of synaptic and free virus transmission, and hence infection multiplicity, can be manipulated in vitro through various means including viral mutants that are deficient in cell free infection and by physical interference with cell to cell contact. In collaboration with Dr. Dominik Wodarz, University of California, Irvine, we are performing a series of integrated experimental and mathematical analyses to tease apart these complex processes.