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Pathogen Detection To Catch Exposure Early, Jett Targets Lymphocytes

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For Marti Jett, the chief of molecular pathology at Walter Reed Army Institute of Research in Silver Spring, Md., catching things early is essentially part of her job description. As an Army researcher, she’s interested in finding ways to rapidly identify patients who have been exposed to pathogens that could be used in warfare. By the time a patient is clinically diagnosed with anthrax, for example, estimates are that person has only a 12 percent chance of beating the disease when treated with the antibiotic ciproflaxin.

In a talk at the Molecular Medicine Tri-Conference this past April in San Francisco, Jett explained her group’s approach to applying gene expression analysis to address this issue. The basic problem, she says, is that there’s little evidence of the pathogen itself in a patient’s blood during the early stages of exposure. So, like a fisherman who searches for tuna only in areas of the ocean where they’re known to congregate, Jett and her colleagues have taken to isolating lymphocytes — the body’s first line of defense against invaders — from a patient’s bloodstream and studying changes in lymphocyte gene expression as a means of determining whether a patient is infected.

Jett’s method of “lymphocyte reconnaissance,” as she refers to the approach, relies on extracting RNA from lymphocytes isolated from blood and using microarrays to identify patterns of mRNA expression that could distinguish between those who’ve been exposed to a pathogen, and those who may just think they’ve been exposed. In work done in collaboration with SRI, Jett found 300 genes expressed in lymphocytes whose changes in expression allowed the researchers to differentiate between exposure to eight types of pathogens.

Jett is particularly excited about recent work that shows this method of diagnosis may also be useful in tracking disease progression. In her experiments, she’s been able to identify variations in gene expression that correlate with distinct time periods after exposure, and she hopes such information will be useful for doctors trying to determine the treatment regimen most likely to succeed in tackling the disease. To do this, she and her collaborators are working to establish a library of gene expression patterns that could be translated into arrays for use in the clinic. “It’s not ready for marketing tomorrow,” she says, “but we’re getting there.”

— John S. MacNeil

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