Sylvester Comprehensive Cancer Center

UM Researchers Publish Breakthrough Findings on the Body’s Immune System

11.17.2004

In a discovery with enormous implications for fighting disease, a team of researchers at the University of Miami School of Medicine has identified a pathway that is activated in response to a viral infection at the very earliest stage. The scientists believe the pathway helps explain innate immunity, the body’s very early detection system that sets off alarms that a pathogen, such as a fungus, virus or bacteria, has contacted or penetrated a cell. The breakthrough findings by the UM scientists are published in the November 18 issue of the prestigious scientific journal Nature.

“Understanding how this innate immune pathway works has huge clinical implications,” said Glen Barber, Ph.D., professor of microbiology and immunology at the School of Medicine and lead author of the study. “As we unravel the pathway further we hope to learn how to regulate the innate immune system to improve vaccines and therapeutic treatments against viral and other pathogen-related diseases, and potentially against cancers caused by viruses.”

It has been known for several decades that the body’s immune system responds to an invading pathogen by making a lot of interferon, which in turn switches on anti-viral genes that destroy the invader. But what has not been clear is how the infected cell recognizes infection to trigger the interferon process.

“The pathway that we found plays a key role in activating these interferons and galvanizing the immune response,” explains Dr. Barber. “In animal cells, once a virus infects a cell, it starts to replicate and reproduce its genome, a process that generates considerable amounts of double-stranded RNA, which is made of nucleic acid. It is the RNA structures produced by viruses that mainly activate the pathway, which requires molecules called FADD and RIP to then turn on the interferon process. When we disrupted FADD or RIP, the virus replicated out of control.”

The UM team also found that the FADD-dependent innate immune pathway they discovered in animal cells also exists against bacteria in Drosophila, the fruit fly. The fact that this pathway exists in the insect world, and has held up through evolution, points to its cellular importance in fighting bacteria and viruses.

Dr. Barber, Siddharth Balachandran, Ph.D., and Emmanuel Thomas, Ph.D., all authors on the Nature article, are currently continuing their work on the pathway through funding from the Defense Advanced Research Program Agency, which is part of the U.S. Department of Defense. Dr. Barber, along with William Harrington, M.D., is co-director of the viral oncology program at UM’s Sylvester Comprehensive Cancer Center.

UM/Sylvester was founded in 1992 to provide comprehensive cancer services and today serves as the hub for cancer-related research, diagnosis, and treatment at the University of Miami School of Medicine. UM/Sylvester handles more than 1,100 inpatient admissions annually, performs 2,800 surgical procedures, and treats 2,900 new cancer patients. All UM/Sylvester physicians are on the faculty of the University of Miami School of Medicine, South Florida’s only academic medical center. In addition, UM/Sylvester physicians and scientists are engaged in more than 150 clinical trials and receive more than $30 million annually in research grants. UM/Sylvester at Deerfield Beach recently opened to better meet the needs of residents of Broward and Palm Beach Counties. This 10,000 square-foot facility at I-95 and S.W. 10th Street offers appointments with physicians from six cancer specialties, complementary therapies from the Courtelis Center, and education and outreach events.

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