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Zealous Mercenaries

A visit with Habib Zaghouani , Professor, Department of Immunology and Microbiology

By Jessica Huang
Published: - Topics: insulin Type I diabetes pancreas injection brain
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In a back corner of the University of Missouri’s medical building, a few floors above the hospital and tucked away to the right, Habib Zaghouani watches a cellular war. He has been up there for seven years, with an army of graduate students and a colony of mice, trying to understand why our bodies attack us and how we can make them stop.

As Professor of Immunology and Microbiology, Director of the Center for Cellular and Molecular Immunology, and the J. Lavenia Edwards Chair in Pediatrics, Zaghouani oversees an ambitious group of twelve graduate students, post-doctoral students, and technical assistants as well as operates four different projects. His research costs about $1.5 million dollars each year, and is funded by grants from the National Institute of Health. But his motivation is simpler than all of that. “I love what I do,” he says. “I do it as a hobby, not just a means of providing for my living. I really like it.”

Zaghouani was drawn to immunology because although the field is similar to genetics, it focuses on humans, not plants. Autoimmune diseases interested him the most. “I always thought the immune system was there to defend us,” he says. “It is like the military branch of our body. But sometimes, like in the military, there are overzealous mercenaries.” He was intrigued that sometimes the body’s military can make serious mistakes.

Zaghouani’s current research combines his curiosity about genetics and his love of immunology. Two of his current immunology projects address the genetic diseases of multiple sclerosis and type I diabetes. His team of graduate students and post-docs play a major role in his research. After giving an overview of his four projects, he brought in each team leader to outline the details.

Haymaker

Graduate student Cara Haymaker describes the parameters of one research program. Using mouse models, the team examines the way certain immune cells attack the myelin coating on nerves in the brain, causing experimental allergic encephalomyelitis in mice and multiple sclerosis in humans. Multiple sclerosis, Haymaker observes, is a painful, paralyzing disease affecting one in every 700 people worldwide – and it has no cure. The disease makes the body’s own cells attack protein in the brain and destroy nerves.

Haymaker and her team have devised an amazing way to calm those overactive immune cells, so they will either leave the brain or do nothing to harm it. When they give a sick mouse a certain protein, the mouse gets better. Much better.

“We will have a mouse that is very sick with almost complete paralysis of the body,” she says, “and we can make that mouse completely better again.” What’s more, they have developed treatment in both injections and pill form. The goal, of course, is to eventually move the research from mice to humans. Once they understand the underlying mechanisms of these treatments, and identify potential side effects, the team plans to pursue human trials.

Tarter

The type I diabetes research has yielded similar results. Danielle Tartar explains that in type I diabetes the body’s immune system kills the insulin-producing beta cells in the pancreas. Often called juvenile diabetes, this disease affects about one in every 400 children in the United States. “We’re trying to remind the body that beta cells are self-tissue and therefore should not be destroyed," she says. "In that way, we’re trying to allow for better insulin production, which will lead to a decrease in blood glucose levels and an overall increase in health. This would also hopefully reduce the need for children afflicted with this disorder to constantly require insulin injections.”

To conduct this research, Tartar and her team use mice that naturally develop diabetes. She explains that the treatment they have developed using this spontaneous model of disease is different from many other diabetes treatments because it targets only the rogue, autoreactive T cells instead of shutting down multiple types of T cells, some of which could be necessary for fighting infection. That means the treatment should cause only minimal side effects.

Zaghouani’s other two research projects focus not on specific diseases, but on the underlying functions of immune cells. One examines the way in which cells of the immune system either die or linger after an infection has been defeated. The other seeks to understand the immune system in newborns, with the hope that someday the research will help create better vaccines for babies.

Ellis

Jason Ellis is in charge of the project that analyzes immune system cells. When a patient is infected, the immune system sends out T cells that kill the pathogen that infects the body, he says. After the infection has been destroyed, most of the T cells die because they are no longer needed. But some of them, called memory T cells, stick around, so the body’s response will be stronger and faster when the pathogen shows up again. Vaccines are based on the immune system’s ability to “remember.” Ellis and his team are trying to figure out how a T cell makes the decision to die or become a memory T cell so that this research can be applied to vaccines. “This would allow them to better design their vaccines and the delivery systems for those vaccines,” he notes, “so that the vaccine is more efficacious and there is less disease.”

Hoeman

Christine Hoeman runs Zaghouani’s final project, in which they seek to understand why newborns get sick more frequently than adults. “If you had a baby or you know a baby, [it seems that] they have fevers every other day and are throwing up every other hour,” Zaghouani remarks. The reason, Hoeman explains, is an excess of the T cells that promote allergies and a lack of the T cells that fight infection. As it turns out, the infection-fighting cells give off signals that the allergy-promoters read as "kill me." Hence, the allergy-promoting T cells, derived from the mother, kill the infection-fighting T cells in newborns. “In the beginning [of life], it is really important to keep the baby as healthy as you can,” Hoeman explains, an imperative that may account for why there are so many of them at the beginning. Ultimately, Zaghouani's team hopes to learn how to fix this imbalance in order to make better vaccines for newborns and keep them from having allergic reactions.

In all of these ways, Zaghouani and his assistants continue to do battle with the smallest rebels of our bodies. Although each new breakthrough calls for more research, someday soon the citizens of our world will benefit from their research into our immune system.