Faculty Profiles

Yuanli Liu
Heather Nelson
Stephen Buka
Barbara Burleigh
Eric Rimm
Karen Kuntz

Department &
Center Highlights

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Virtually unknown in the United States, Chagas' disease is rife throughout Latin America, where it strikes at the hearts of 20 million people. Chagas begins when a one-celled parasite, Trypanosoma cruzi, emerges from the gut of beetles living in thatched roofs. Deposited in the bugs' feces upon human skin, T. cruzi travels from the moist linings of rubbed eyes and noses into the bloodstream, then burrows into organs and tissues. For reasons unknown, the immune system can clear T. cruzi from every part of the body except the smooth muscle cells of the heart and gastrointestinal tract, where in up to 30 percent of people it sets off inflammation. The heart, struggling to compensate for lost efficiency, becomes greatly enlarged, and eventually gives out.

Parasitologists are fascinated and bedeviled by T. cruzi, which manages to thrive and replicate within muscle cells for up to 30 years before killing its human host. In recent years, this protozoan has commanded attention from American blood-banking authorities, who warn that blood donations from immigrants who don't know they are infected pose an emerging threat. The U.S. Food and Drug Administration will mandate screening for T. cruzi as soon as a test becomes available later this year. Although risk for the nation is only 1/25,000 overall, a study in 1998 put the odds in Los Angeles at as high as 1 in 5,400.

Like scientists in Brazil, Mexico, and elsewhere, Barbara Burleigh, 40, wonders why T. cruzi proves benign in more than two out of three human hosts. Why is heart muscle a safe harbor for this deadly invader? But unlike other researchers, most of whom are immunologists, Burleigh is taking a novel tack. Instead of focusing on the immune system's response to T. cruzi, she wants to know how the parasite fools the cell and sets up housekeeping. Interfering with this process could clear a way to curing Chagas' disease, or at least controlling it.

Considering T. cruzi from the host cell's perspective sets Burleigh apart from other parasitologists, according to Burleigh's department chief, Dyann Wirth, herself an expert on the malarial parasite. "As a cell biologist, Barbara is a pioneer, coming in from a completely new field," Wirth says.

"We're asking, 'How does this parasite gets its teeth into the host to begin with?'" says Burleigh. "How does T. cruzi modify the host-cell environment so it can grow and multiply?" T. cruzi may be unique among intracellular pathogens, she believes, in that it sneaks into cells undetected. Once inside, the protozoan hunkers down inside a membrane-lined capsule, waiting several hours before it escapes. At that point, at least in cell culture, T. cruzi starts tripping gene switches in the cell. By activating genes that make heart muscle more contractile, for example, it initiates the first steps toward heart enlargement.

Quite by accident, Burleigh's team has discovered that T. cruzi puts a big damper on genes that normally control the continual buildup and breakdown of fibrous tissue. "Fibroblast cells in muscle and other tissues continuously make and dismantle collagen and matrix proteins. But T. cruzi interrupts this cycle by interfering with messenger molecules called cytokines," Burleigh explains. These cytokines represent potential targets for new drugs that could be developed to control fibrotic diseases, including scleroderma and the excessive scarring seen in burn patients.

In a year or two, Burleigh hopes to have at her fingertips powerful technologies that will allow her to study the genetic changes occurring simultaneously in T. cruzi and its host cell. Such advances herald "a new era," she says, one that could change for all time how scientists study the interplay between parasites and their hosts.

Just as exciting, Burleigh adds, is the prospect of being able to devise treatments for the first time for many devastating parasitic diseases. "Ten years ago, it was a pipe dream to think that even if I identified a good drug target, a drug company would be interested in picking it up," she says. But given ever more potent technologies, "biologists in public health, along with chemists, may one day be empowered to develop drugs themselves."

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Photo: Kent Dayton