Proteomic pattern profiling is not necessarily just for cancer: According to two members of the NCI’s Early Detection Research Network for biomarker research, it may also help solve one of the health mysteries that emerged in the wake of the 9/11 terrorist attacks.
John Semmes, an associate professor at the Eastern Virginia Medical School in Norfolk, Va., is working with collaborator Bill Rom, professor of environmental medicine at New York University, to discover whether differences in protein expression patterns could help explain why some firefighter veterans of the World Trade Center rescue effort developed a chronic respiratory condition — commonly called “World Trade Center cough” — while others recovered from more temporary conditions.
“These firefighters go in and they breathe in all these terrible elements, and most of them recover from these upper respiratory things, but about a hundred or so have not recovered. And the big medical question is, ‘What is it and why?,’” Semmes says.
So far he is not ruling out more traditional environmental factors as the explanation for differences in firefighters’ reactions. That’s why he is first waiting for the firefighters’ New York-based physicians to gather complete histories on each of the patients for which Semmes’ group is receiving a serum sample before he plunges into serum pattern profiling.
“You want to determine the biological phenomenon that’s occurring,” Semmes says. “Is this a separate biological entity, or are you going to be able to explain it because they have a lot of other mitigating circumstances? Maybe they smoke a lot — maybe we’ll find that everyone who has the chronic ailments also are heavy smokers.”
If the mitigating factors, however, can’t explain everything, that’s when Semmes will be ready to step in with the pattern analysis of serum samples.
Semmes’ group plans to use a combination of approaches to find differentially expressed protein patterns and to identify the proteins involved. In the first run, the sera samples will be run through what Semmes calls “the tried and true path using the SELDI type of profiling approach,” but with one change: the scientists will first use Bruker Biosciences’ automated magnetic bead front-end affinity separation kit before depositing the samples on the SELDI chips, “so we can get eventual deposition onto the desorption surface to be more uniform,” Semmes says.
Once he finds peaks of interest, Semmes says he will then run the serum through a second run in which affinity beads are again used to isolate the proteins, before running the sample on a multidimensional separation system and then through Bruker’s new Ultraflex TOF/TOF tandem mass spec analysis to identify the proteins.
Finally, the TOF/TOF identifications will be verified through immunoassay-type traditional experiments. “If indeed they are the proteins that we think they are, then we have a hit,” he says. “If it’s an interesting protein that might have some relationship to how the disease might develop, then you’re golden. If it’s not, then you go and look for another one.”
Semmes says he hopes to have some preliminary results from the experiments by the middle to later part of this year.
The ultimate goal of all this work would be an understanding of the mechanisms to the point of possibly developing a therapeutic. Semmes says that all the information would be “freely exchanged” with anyone else around the country doing research on a similar group of people.
An expanded version of this column appeared in ProteoMonitor’s January 9, 2004, edition.
Katherine A. Mason is editor of ProteoMonitor, a weekly newsletter from GenomeWeb at www.proteomonitor.com. She can be reached at [email protected] genomeweb.com.