As a graduate student pursuing a doctoral degree in Microbiology and Immunology in the laboratory of Dr. William Jacobs Jr. at The Albert Einstein College of Medicine, Amanda developed an interest in macrophage-pathogen biology. The pathogen was tuberculosis, a bacterium that use multiple mechanisms to evade the host response to persist and grow inside macrophages.
Interested in the idea that the ability to persist in a hostile intracellular microenvironment would require protein secretion machinery, she developed an approach using resistance to azide to clone and characterize the mycobacterial homolog of the central secretory factor known at that time, as SecA.
Ready to move on to postdoctoral studies, the field of HIV/AIDS was attractive as no cure or vaccine was and as yet remains several years away, she joined the laboratory of Dr. Cecilia Cheng-Mayer at the Aaron Diamond AIDS Research Center.
HIV is another microbe which has a variety of ways to escape from the immune response and to replicate and persist within tissue macrophages and as a latent reservoir in T-lymphocytes. In order to more readily study HIV-macrophage biology, Amanda spearheaded the cloning of the first recombinant HIV virus. This virus expresses all HIV viral proteins, can reproduce in human macrophages and mark the infected cell with a green fluorescent protein tag.
The presence of the tag allows infected cells to be detected and/or isolated from cultures using a variety of technologies including fluorescent microscopy and fluorescence activated cell sorting. The reporter virus became a central tool in future studies in which she showed that:
- MHC class I molecules, which are important for immunity, are down-regulated on HIV-infected macrophages by the viral protein Nef
- HIV-infected primary human cultured macrophages can serve as a viral reservoir and modeled in vitro
- A cell surface activation signature is prominent on macrophages that are actively producing virus and that HIV Nef, is in part, required for the phenotype
Amanda joined the Department of Neurology at Johns Hopkins School of Medicine in 2004 where she had the opportunity to work with Dr. Suzanne Gartner who was one of the first to characterize HIV infection of macrophages. Here, Amanda’s interest in HIV-macrophage pathogenesis took on an additional translational focus. Macrophages are present in most tissues including the brain where there are additional subpopulations like microglia that have specialized functions.
Now, an Associate Professor at Hopkins, research in Amanda’s laboratory investigates how inflammatory processes in the brain induced by HIV leads to cognitive impairment in HIV-infected individuals. Current experimental methodology includes the use of primary cell culture and clinical material, and a small animal model is being launched to test hypotheses. The ultimate aim of her group’s research program is to identify the critical cellular pathways involved in HIV-mediated neuropathogenesis and to, in a collaborative manner, develop novel therapeutic strategies.
Having completed research internships during the summers while doing undergraduate studies, Amanda’s firsthand positive experiences with such programs today inspires her to provide such avenues for the next generation of scientists from diverse backgrounds. Information on these programs which she directs or co-directs can be found at the following links:
1.www.projectpipelinebaltimore.com
Inflammation & Neurodegeneration in HIV-Associated Neurocognitive Disorders (HAND) 