Albert Fornace Jr: What are the Biomarkers of Radiation Damage?

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It’s an inside joke for sure, but Albert Fornace Jr., MD, was called the “Man from GADD” for quite a few years – a twist on the old TV commercial featuring the Man From Glad.

That’s because Fornace, the molecular research chair at the Lombardi Comprehensive Cancer Center and professor of Biochemistry and Molecular & Cellular Biology, had been working on so-called GADD (growth-arrest and DNA-damage inducible) genes which were discovered by his laboratory and which are activated by many types of damaging agents, including radiation and environmental stresses. In 1992, he was senior author on a study showing that the p53 tumor suppressor gene, which is mutated in a majority of cancers, turns on GADD45a to modulate tumor formation, and thus demonstrated for the first time that p53 functioned by regulating gene expression. GADD45a and subsequently other p53-regulated genes can protect an organism against cancer and it can also send a stressed cell into suicide – so this pathway is key to maintaining cell health.

One point behind his “Man from GADD” pun is that the GADD45a study, along with subsequent papers on stress signaling involving p53 and other tumor suppressors, have had major impacts in the cancer and stress-gene fields, such that Fornace is in the top 0.5 percent of cited authors in this field.

Fornace, who came to Georgetown University Medical Center (GUMC) in late 2006 after years of research at the National Institutes of Health (NIH) and at Harvard School of Public Health, is now using a systems biology approach to investigate the intricate network of signals that are turned on when a cell is stressed, such as when it has been exposed to radiation or when it is in a precancerous state. A new avenue of research in this area, known as metabolomics, involves searching for a fingerprint of small molecule metabolites—products of chemical reactions— in blood or tissues.

That work is designed to offer some very practical benefits, he says. With support from the NIAID’s biodefense program and the National Aeronautics and Space Administration (NASA), he is using metabolomics to study radiation damage. One project is to understand the very real risk that radiation in space has on astronauts and another is to develop a biomarker test that can easily detect radiation damage in blood. “Imagine if a dirty bomb goes off in a large city, and few people are exposed,” he says. “Now, without a test, 5 to 10 million people would overwhelm medical facilities as well as empty out of the city, but if a test was available, people could be assured that they have not received significant exposure and would probably remain.

“That would mean that we could tell many people that they have not been exposed, and we could treat those who were,” he says. The instrumentation is already available to measure small molecules – such as that now being used in explosives detection – so expectations are that “such a biomarker test would take years to develop, not decades,” Fornace says.

He says GUMC is a good place for this kind of research. “There is a critical mass of strong scientists and good facilities here. It’s well funded, and, well, collegial…. What more could I want?”

By Renee Twombly, GUMC Communications