2001

GABRIEL NUÑEZ

Professor of Pathology, University of Michigan

BROAD MEDICAL RESEARCH PROGRAM

Many people don’t understand how debilitating inflammatory bowel disease is. Even as a doctor and immunologist, I wasn’t fully aware until I began studying Crohn’s disease. If you’re one of the 1.6 million Americans afflicted, symptoms can start when you’re just a few weeks old, or maybe when you’re a teenager, and you’ll deal with it the rest of your life. It’s not fatal, but it’s painful and incapacitating and has all kinds of complications, some requiring surgery. It can have a damaging psychological effect on individuals, particularly young people. Frustratingly, not only do we not understand how to treat Crohn’s, we don’t know the full scope of its causes.

In 1998, a gene called NOD2 changed our entire research program. In collaboration with Dr. Judy Cho, then at the University at Chicago, we found that mutations in NOD2 make an individual more susceptible to Crohn’s. Everybody has thousands and thousands of mutations in their genome; it’s part of what makes us different from our neighbors. Some of these mutations, however, can make you susceptible to a disease. The link of NOD2, a protein that recognizes bacteria, to Crohn’s disease was a seminal finding that changed how we think about its cause.

When The Broad Foundation established the Broad Medical Research Program (BMRP) in 2001, I immediately applied for funding. We were lucky to receive two grants to continue our work, and they came at a critical time. We used the funds to generate stronger data, which helped us secure additional grants to complete two large-scale studies. The BMRP was instrumental for investigators who needed support early in their projects. The Broad Foundation was taking a risk on younger, more experimental work that wouldn’t be funded in the traditional way. It was also supporting work all over the world, which inspired international collaboration.

Since BMRP’s founding, our understanding of Crohn’s disease has changed radically through a deeper knowledge that suggests bacteria normally residing in our gut can trigger Crohn’s attacks in individuals with NOD2 mutations. We still don’t know exactly which bacteria are the “bad guys” here, but we’re getting closer. Eventually, if we can block the disease-causing bacteria, we can prevent the severe attacks that make it so challenging for people with Crohn’s to go about their daily lives. It won’t be long before we identify these triggers and translate that underlying knowledge into treatments.