News Release: Research, School of Medicine
Jan. 26, 2009
Emory Leads $13 Million NIH Study of Key Protein in Chronic Infectious Diseases
Initial seed funding from Concerned Parents for AIDS Research leads to key discoveries and NIH grant
A grant in support of AIDS research from parents who in 1989 realized that all children are at risk for contracting the disease, has paved the way for a much larger NIH grant that could lead to promising new treatment targets.
Concerned Parents for AIDS Research, a New York-based group of parents, some of whom have lost children to AIDS, last year contributed $250,000 to the Emory Vaccine Center, led by Rafi Ahmed, PhD, a Georgia Research Alliance Eminent Scholar. The seed grant made it possible for Ahmed's laboratory to collaborate with scientists at Harvard University on studies of a protein that inhibits the immune response to chronic infectious diseases like HIV.
Two years ago scientists at Emory and Harvard made the exciting discovery that the immune inhibitor protein PD-1 (Programmed Death-1) helps switch off the immune response to chronic infectious diseases. This results in apparent "exhaustion" of the T-cell response.
Because of the progress made through the initial seed grant, the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH) has awarded a $13 million, five-year program project grant that will allow the Emory scientists and their collaborators to focus on PD-1 and its specific role in HIV and other chronic viral infections. They plan to identify new targets and pathways and possible drugs that could aim for this molecular trigger, turn off the PD-1 protein, reactivate the immune response and possibly clear HIV infection.
"Emory put together amazing teams to leverage our private funding," says Dr. Andrew Lipschitz, medical director of Concerned Parents for AIDS Research. He believes that future success in stopping AIDS depends on sharing ideas, sharing technology and sharing costs.
"CPFA’s goal was to bring together great scientists at two great universities," he says. "Our initial grant made sense because Emory had certain techniques and equipment that Harvard did not and vice versa. Duplicating machinery and planning would have been very expensive. By sharing their ideas and technology, Emory and Harvard were able to increase their understanding of PD-1 and qualify for this NIH grant, which will enable collaboration with many other major institutions and help scientists move more quickly toward finding treatments and cures for HIV."
With the NIH grant, the research team now includes scientists from Emory, Dana Farber Cancer Institute, Harvard Medical School, Massachusetts General Hospital, New York University, the University of Montreal and the University of Pennsylvania.
"It is now well established that T cell dysfunction is a cardinal feature of many chronic viral infections – most strikingly HIV, and also hepatitis C and hepatitis B. We have found that the PD-1 inhibitory pathway plays a critical role in this functional exhaustion of virus-specific T cells," says project leader Ahmed.
"This collaborative grant, which includes an outstanding team of investigators, provides us a fantastic opportunity to investigate the unique properties of this PD-1 pathway that inhibits the immune response and impacts our defense against deadly infectious diseases. Our work also has clear implications for the treatment of tumors and autoimmune diseases and for increasing the success of transplantation."
In recent research in which they blocked PD-1, Emory scientists were able to safely and significantly reduce the plasma viral load and prolong survival of rhesus macaque monkeys severely infected with simian immunodeficiency virus (SIV), the nonhuman primate version of HIV. The therapeutic strategy worked by boosting the function of anti-viral killer cells (CD8 T cells) and improving antibody response to the virus. Rama Amara, PhD, a scientist at Yerkes National Primate Research Center and the Emory Vaccine Center, led the research along with scientists at Dana-Farber Cancer Institute, Harvard Medical School and the University of Pennsylvania Medical School. The research was published online in Nature Dec. 10, 2008.
Emory scientists involved in the new NIH program project grant include Ahmed and microbiologists Jeremy Boss and Brian Evavold. Other collaborators include Michael Dustin (Skirball Institute, New York University), Gordon Freeman (Harvard Medical School and Dana Farber Cancer Center), James Riley (University of Pennsylvania), Rafick-Pierre Sekaly and Elias Haddad (University of Montreal), Arlene Sharpe (Harvard Medical School), and Bruce Walker and Daniel Kaufmann (Harvard Medical School, Massachusetts General Hospital and Howard Hughes Medical Institute).
Articles in Nature describing research on the PD-1 pathway:
"Enhancing SIV-specific immunity in vivo by PD-1 blockade." Velu, V., Titanji, K., Zhu, B., Husain, S., Pladevega, A., Lai, L., Vanderford, T.H., Chennareddi, L., Silvestri, G., Freeman, G.J., Ahmed, R., Amara, R.R. Nature Online Publication Dec. 10, 2008
Nature 443, 350-354 (21 September 2006) | doi:10.1038/nature05115.
Nature 439, 682-687 (9 February 2006) | doi:10.1038/nature04444.
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The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service. Its components include schools of medicine, nursing, and public health; Yerkes National Primate Research Center; the Emory Winship Cancer Institute; and Emory Healthcare, the largest, most comprehensive health system in Georgia. The Woodruff Health Sciences Center has a $2.3 billion budget, 17,000 employees, 2,300 full-time and 1,900 affiliated faculty, 4,300 students and trainees, and a $4.9 billion economic impact on metro Atlanta.
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