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Recent research at TUSM sheds light on certain white blood cells that might help the scientific community get closer to the development of an HIV/AIDS vaccine
By Mark Wolverton
Featured Fall 2010 Article
Jay Rappaport and Michael Kogan, 5th year MD/PhD student in the School of Medicine, discuss Rappaport's research in the Department of Neuroscience laboratory. Photo by Joseph V. Labolito, Temple University
Even when he was 8 years old, Jay Rappaport knew he was going to be a scientist: He proclaimed it in a short biography he wrote as a school assignment.
Written in pencil on a single sheet of lined paper, the document now hangs on the wall in Rappaport’s office in the new Medical Education and Research Building at the Health Sciences Center. His mother framed it and presented it to him when he graduated from the University of Pennsylvania with a PhD in microbiology. “I didn’t even know she’d kept it,” he admits.
More than 20 years later, Rappaport is still a scientist and a dedicated researcher
Now a Professor of Neuroscience and Neurovirology, Director of the Biomedical Neuroscience Graduate Program and Associate Chair of the Department of
Toward the Center
After his early work with Gallo and stints at the National Institutes of Health (NIH) in Bethesda, Md.; University of California, San Diego; and Mt. Sinai Hospital in New York City, Rappaport returned to Philadelphia to form the Center for Neurovirology at Hahnemann University Hospital with Kamel Khalili, Chair of the Department of Neuroscience and Director of the Center for Neurovirology at Temple. Neurovirology comprises several related disciplines, including neurology, virology and molecular biology, to study viruses that invade and affect the nervous system.
In 1999, the center relocated from Hahnemann to Temple as part of the College of Science and Technology. Now part of the School of Medicine—a hub for NIH-funded protocols and clinical trials in neurodegenerative and neuromuscular diseases—the center researches the neurological effects of conditions such as HIV/AIDS, Alzheimer’s disease, multiple sclerosis and Parkinson’s disease.
It is routinely ranked in the top 15 of all neuroscience departments for NIH funding. And recent NIH funding will establish the new Institute for Translational Neuroscience.
A Different Approach
Rappaport’s interest in AIDS pathogenesis—the way the disease takes hold in the body—and how it manifests in the central nervous system set him on a new
The common mechanism, he believes, involves monocyte macrophages, a type oF white blood cell subverted by HIV when it infects a person. By zeroing in on these alternate pathways to AIDS infection, Rappaport has forged another way to understand and deal with HIV, providing invaluable clues to a part of the puzzle.
Since the 1980s, a great deal of HIV/AIDS research has concentrated on CD4+T cells, the deterioration of which is used to mark the progress of the disease. However, Rappaport focuses on macrophages, which normally attack and consume invading microbes. “Macrophages are a major reservoir for HIV infection that remains unaddressed right now,” he says.
Some monocytes (a type of white blood cell) leave the bloodstream to enter the
“We were able to correlate the expansion of this subset with increases in viral load. At the same time, we found that the subset expands in relationship to how low the CD4 count is,” he explains. In other words, as the virus multiplies, the population of monocyte macrophages increases, while the number of CD4+T cells decreases. These HIV-infected macrophages cause trouble in the central nervous system. “They accumulate around blood vessels and they secrete not only virus, but also some inflammatory cytokines that cause damage to the nervous system,” Rappaport says. “Cytokines” are proteins that communicate with cells, causing them to react to the signals cytokines send.
“We think that what happens early in infection is, the virus enters the central
This finding contradicts an earlier “Trojan horse” model commonly held among most researchers, which proposed that HIV-infected macrophages enter the nervous system immediately upon infection and lie dormant for a time, emerging later to re-infect the body. Instead, Rappaport says that diseased macrophages are activated, enter the circulatory system and are transported to the nervous system to invade it.
Learning more about the effects of HIV-infected macrophages on lymphocytes could provide significant insight into how the infected cells compromise the immune system.
Aiming for a Vaccine
But Rappaport believes that targeting this altered set of monocyte macrophages can lead to new therapeutic treatments and to a vaccine. “There has to be a way to get the immune system to eliminate them or to target specific survival pathways to enable them to undergo cell death,” he says. “I hope that the work we’re doing in trying to investigate the pathogenesis of AIDS in the central nervous system will lead us back to how to generate an effective vaccine.”
In July, Rappaport was awarded a five-year grant from the NIH/National Institute of Mental Health. The next step of his research will be to “bring the changes in the
After almost a quarter-century of fighting HIV/AIDS, Rappaport believes that a cure—or at least a vaccine—is now within reach.
“I think we’re almost there,” he says. “We’re able to extend people’s lives, control the virus and stay ahead of its mutations by multiple drug therapies.” But, he adds, “It’s a matter of time and effort and some creativity to come up with something that really works. We need some new approaches and some new ideas.”
To read more about the new Institute for Translational Neuroscience at the new Medical Education and Research building, click here.
Mark Wolverton is a freelance writer whose work has appeared in various national magazines, such as Air & Space/Smithsonian and Popular Science.
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