Sylvester Comprehensive Cancer Center

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


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.


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