showing what a game changer it can be to have some of the world’s leading experts in one field, ready to collaborate, right across campus. “If it wasn’t for Gene and his group, Vanessa particularly, we couldn’t have gotten this thing off the ground,” Sisodia said. “Jack Gilbert and Gene and the others are providing us all kinds of services and technologies to do this stuff, like deep gene sequencing. It’s something we wouldn’t know how to do, and they have all the capacity to do all the computational work for us.” PHOTO BY NANCY WONG
to organ transplants. Transplantation is a critical, lifesaving procedure — the body needs a new organ to survive — but the immune system does everything it can to reject it as a foreign invader, just as it would a bacterial infection or virus. Even with an organ donated from a close, genetically matched relative, transplant recipients usually have to take medication the rest of their lives to suppress the immune system response and prevent rejection. Success rates for transplants of skin, lungs and intestines — organs exposed to the outside world — are much lower than for transplants of internal organs such as kidneys and hearts. That’s true in both clinical settings for humans and in laboratory models. One hypothesis to explain this difference is that skin, lungs and intestines are colonized by microbiota whereas sterile internal organs are not.
A better understanding of the role microbes play to prime or suppress the immune response could lead toward new strategies to improve transplant outcomes in humans.
Marisa Alegre, MD, PhD ’93, and her team are studying the role microbiota play in the body’s ability to accept transplanted skin and other organs. In a recent study, the researchers demonstrated that skin grafts in mice treated with antibiotics prior to transplantation survive longer.
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ccess to in-house microbiome expertise and technical facilities at UChicago is helping researchers explore the impact of the microbiome on other unlikely areas. Maria-Luisa Alegre, MD, PhD’93, is a professor in the Department of Medicine who studies how the immune system behaves in response to infections, autoimmune diseases and cancer. Her lab’s main focus now, though, is organ transplantation, specifically the body’s mechanisms that either help tolerate or reject a new organ. As with autoimmune diseases, the immune system can be the body’s own worst enemy when it comes
THE UNIVERSITY OF CHICAGO MEDICINE AND BIOLOGICAL SCIENCES DIVISION
Earlier this year, Alegre and her team tested this hypothesis with the help of special “germ-free” mice from the Gnotobiotic Mouse Facility. The germ-free facility is a resource within the Animal Resources Center at UChicago, in partnership with the Digestive Disease Research Core Center, directed by Chang and Bana Jabri, MD, PhD, a professor in the Department of Medicine who focuses on celiac disease. Gnotobiotic or germ-free mice are born and raised in a tightly controlled, sterile environment so that they have no bacteria or viruses living on their skin or in their guts. This makes them excellent models for microbiome research, because scientists can track physiological changes after introducing different strains of bacteria, changing their diet or introducing non-sterile companions. In a study published in June, Alegre and her team showed that skin grafts between mice treated with antibiotics prior to transplantation survive roughly twice as long as mice that didn’t receive the medications. Grafts between mice raised in a sterile, germ-free environment also survived longer. Meanwhile, the team found that if germ-free mice were dosed with microbes from conventional, untreated mice, they rejected the skin grafts more