Center for Proteomics and Bioinformatics:
|2001||M.D., Yale University School of Medicine, New Haven, CT|
|2001-2006||Clinical research fellow, Clinical and Molecular Retrovirology Section, National Institutes of Allergy and Infectious Diseases. Bethesda, MD|
|2006-2010||Senior research investigator, Department of Microbiology, University of Pennsylvania. Philadelphia, PA|
|2010-||Tenure-track Assistant Professor, School of Medicine, Case Western Reserve University, Cleveland|
|2000||HHMI-NIH Research Scholar|
|2001-2005||NIH Special Act Award|
Research in the Tilton laboratory is focused on understanding the factors that make cells susceptible to viral infection. Using flow-cytometry based technologies, we have developed assays that enable identification of CD4+ T cells that are susceptible to HIV-mediated viral fusion and productive infection. We have found that the number of cells that are susceptible to viral-mediated fusion far exceeds the numbers of cells that become productively infected, suggesting a post-entry block to viral replication in the majority of cells. Moreover, CD4+ T cells exist in many functionally-distinct subsets that vary in their susceptibility to HIV infection, and understanding how infection of particular subsets of cells is involved in the pathogenesis of HIV infection is a major goal of the laboratory. Current efforts in the Tilton lab include:
1. Discovering cellular factors that regulate susceptibility of cells to HIV infection.
Based on the observation that the majority of cells that are susceptible to HIV-mediated fusion do not become productively infected, we are interested in the dynamics that control the outcome of a fusion event. We hypothesize that cell susceptibility to viral infection is a consequence of the relative abundance of factors that favor or disfavor viral replication. For instance, an activated cellular metabolic state and presence of host proteins commandeered by the virus would favor viral replication whereas an interferon-induced antiviral state or the presence of innate viral restriction proteins (such as Apobec-3G, TRIM5-alpha, and tetherin) would inhibit viral replication. We are using our flow cytometry-based HIV infection assays to isolate cells that susceptible or resistant to productive infection by HIV and probing these cells for the biological pathways and individual proteins that collectively determine the outcome of a virus-cell interaction.
2. Defining the subsets of CD4+ T cells that are infected by HIV.
Using multiparametric flow cytometry, we are able to precisely identify the susceptibility of CD4+ T cell subsets to fusion and productive infection by HIV. We are interested in identifying which cells are most susceptible to HIV in uninfected patients, and determining what happens to these cell populations in HIV-infected patients. Recent studies suggest that which CD4+ T cells are infected by HIV may be a major driving factor in the pathogenesis of HIV infection, and is a major research aim of the laboratory.