Investigations

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On September 21, in a determined effort to attack a phalanx of common and debilitating diseases through its genetic underbelly, an army of mice, patient samples, and geneticists invaded the newly constructed Martin Boyer Laboratories. On the fifth floor of the former Billings Hospital, the labs were created to take the war on inflammatory bowel disease (IBD) to a new front, by going after their inherited origins through the genes of families with multiple cases of IBD and by testing the effects of those suspect genes in mouse models. Although lobbying for the space and designing and building the center took more than two years and required nearly $4 million in financial support, the researchers say that the space, and the kinds of work that it allows, was worth the wait.

"I know of no other laboratory quite like this in the world," says Joseph B. Kirsner, PhD'42, the Louis Block distinguished service professor of medicine and author of the first scientific paper, in 1948, on the inheritance of IBD. Kirsner and gastroenterology researcher Eugene B. Chang, MD'76-the Martin Boyer professor of medicine and the new labs' director-were instrumental in pulling together financial backing for the project, including support from the Boyer family, the Gastrointestinal Research Foundation, and others.

Inflammatory bowel disease is a broad term for two painful conditions known as Crohn's disease and ulcerative colitis. Led by Kirsner and Stephen Hanauer, U of C physicians have been pioneers in improving care, testing new therapies, and searching for a cure since the 1930s. The staff cares for more than 5,000 patients with IBD, including many families with a predisposition to IBD. But despite years of study of the disorders' epidemiology, biochemistry, and immunology, the cause-how genes, lifestyle, and environment interact to trigger uncontrolled inflammation-remains unknown.

Two Boyer Lab researchers, human geneticist Judy Cho and molecular immunologist Averil Ma, will use genetic tools-including information from the newly completed Human Genome Project-to unravel the complicated events that initiate these disorders and to develop more specific therapies to treat the disease, not just the symptoms.

The inflammatory bowel diseases are not simple, single-gene disorders, and the researchers expect to find multiple genes, in the range of seven to nine separate but perhaps interrelated genes that increase a person's risk for IBD. Two years ago, Cho led a team that performed the largest, most comprehensive genome-wide study ever done of patients with inflammatory bowel disease. The team identified regions on chromosomes 1, 3, and 4 that appear to contain genes that could trigger the disease's onset. They also confirmed the role of one previously localized gene named IBD1, near the center of chromosome 16, that appears to act in concert with the disease gene on chromosome 1.

While Cho looks for clues in patients' DNA, Ma works with mice, and their three-day-old embryonic stem cells, to "interrogate" how specific genes that may be involved in IBD work. His sections of the lab consist of two tightly controlled areas for sensitive tissue-culture research. One room is devoted to manipulating the embryonic stem cells to generate gene-altered mice; the other room is used for studies of the mice's immune response to various stimuli, and how altered genes can affect the immune response to infections and the process of inflammation. Ma is particularly interested in the role of substances that affect the immune response, and how the body regulates its response to these potent molecules.

The new research space and equipment will save time, energy, and money, says Ma. Before the lab opened, he had to send members of his team to Atlanta to perform certain essential experiments, waiting for results before arranging follow-up tests-an expensive, slow, and inefficient process. Now, he says, "We should be able to make much more rapid progress."

"The center is committed to making a difference in the lives of people with IBD," says Chang. "It's the crucial next step in the long battle with this disease."

- Jennifer Fortney