Federal University of Santa Catarina
Dr. Báfica is an assistant professor of immunology at the Federal University of Santa Catarina, Brazil.
As a young medical student at the Federal University of Bahia in Brazil, André Báfica loved the intensity of emergency medicine. Although he planned to become an ER physician, he soon grew passionate for the field of tropical infectious diseases. He joined an immunology lab that provided a great deal of satisfaction. “Anything you can think of, you can test it yourself,” he says. “This is no job. It’s simply pleasure.”
Báfica fondly remembers marathon lab sessions with one of his medical school mentors, visiting fellow Johan Van Weyenbergh, that lasted until 2:00 or 3:00 A.M. “We’d discuss during the day and work during the night,” he says. The long hours paid off when the pair discovered a survival trick of the parasites that cause the tropical disease leishmaniasis, a serious problem in Brazil. The parasites spur cells to release molecules known as type I interferons, which enable the invaders to establish themselves in the body. Báfica also joined a clinical research project, under the supervision of Aldina Barral and Jackson Costa, and helped show that a drug prescribed for sluggish circulation heals the disfiguring skin ulcers associated with leishmaniasis.
This varied experience convinced Báfica that he could have “the best of both worlds—tropical medicine and basic research.” But he recognized that to continue in science, he needed a Ph.D., since, he says, M.D.s cannot be individual investigators on research grants in Brazil. During his Ph.D. research at the Oswaldo Cruz Foundation, Báfica worked with immunologist Manoel Barral-Netto to decipher how the tuberculosis (TB) bacterium meddles with the body’s production of interleukin-12, an immune system signal that promotes attacks on pathogens.
He continued the work on TB as a postdoctoral fellow in immunologist Alan Sher’s lab at the U.S. National Institutes of Health and took an interest in another major worldwide plague, HIV. In combination, the two pathogens cause a different and more severe illness than either does alone.
“It’s not A plus B, it’s A times B,” Báfica explains, partly because the TB bacterium stimulates cells to manufacture more copies of HIV, and HIV impairs immunity against TB. In 2003, he and his colleagues revealed that this virus-promoting effect requires a specific pathogen-detecting protein, Toll-like receptor-2, that occurs mainly on immune cells. That discovery suggested a possible way to slash levels of HIV in people who have TB.
Báfica also uncovered several aspects of the body’s mechanism for controlling the TB bacterium. The microbe sparks a reaction from the immune system, but an excessive response can be harmful. As Báfica found, the body produces molecules called lipoxins that can tone down the immune reaction provoked by the bacterium, thus possibly averting self-inflicted damage. The paper was published in the Journal of Clinical Investigation, and other labs are following up on this discovery, trying to determine whether blocking lipoxins can treat TB.
That same year, Báfica and colleagues reported that two kinds of Toll-like receptors work together to battle the TB bacterium. One receptor helps mobilize chemical defenses, whereas the other enables immune cells to gain access to lung tissues where the bacterium hides. The paper, published in the Journal of Experimental Medicine, was one of the first to show cooperation between such pathogen-detecting molecules.
Since 2007, when Báfica started his own lab at the Federal University of Santa Catarina in Brazil, he and his colleagues have zeroed in on one of the TB bacterium’s potential weak spots. Last year, they discovered that the microbe manufactures a protein, called sMTL-13, that the human immune system can recognize. The lab is now working to nail down the protein’s function, identify the pathogen-detector molecules that enable immune cells to spot sMTL-13, and determine what parts of the molecule immune cells key on. Ultimately, they want to know if the protein can boost the effectiveness of potential vaccines against TB.
Báfica also wants to understand why many people infected with TB show no symptoms of disease. Although the TB bacterium infects about one-third of the world’s people, only 5 to 10 percent of them fall ill. Determining how some people keep the bacterium in check might lead to better treatments for those who don’t. “The major challenge is to understand what’s going on with the people who control the disease,” says Báfica.