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Aequanimitas - The Road from Rheumatology to Cancer
Aequanimitas Fall 2014
The Road from Rheumatology to Cancer
Date: October 23, 2014
Even before he began his Osler residency 23 years ago, Antony Rosen found rheumatology intriguing. “The diseases are incredibly enigmatic, and I love the hunt,” he says. “I lie awake at night thinking about them.”
“Good ideas,” says Antony Rosen, “come from a slow hunch—a growing body of information focused on human clues.”
Now, as new vice dean for research, Rosen leads a research enterprise that receives more federal support annually—in excess of $574 million in 2013—than counterparts at other U.S. medical schools. First on his to-do list, he says, is encouraging people “to think about diseases in old and new ways.”
It’s advice borne of experience.
Over the past 10 years, having observed a large number of patients with rheumatic diseases develop cancer, Rosen became convinced of a “strange confluence” between cancer and autoimmunity. So he brainstormed with Scleroderma Center Director Fred Wigley, rheumatology researchers Livia Casciola-Rosen and Ami Shah, and the cancer genetics group of Bert Vogelstein and Ken Kinzler. Together they launched a study using blood and tumor tissue samples from 16 patients with both scleroderma and different kinds of cancer.
Patients with scleroderma, explains Rosen, often make antibodies to a protein called RPC1. The antibodies likely cause the organ damage characteristic of the disease. Although the reason behind this antibody production remains unknown, a breakthrough came in 2013, when Rosen, Vogelstein and colleagues showed that cancers from a majority of patients with scleroderma with antibodies to RPC1 had a mutation in the gene POLR3A, which codes for RPC1. These alterations created a foreign form of RPC1 that appears to trigger an immune response.
These findings suggest that scleroderma represents a powerful immune response to cancer, which cross-reacts with the patient’s own tissues and causes disease. In the patients with scleroderma without a discernable cancer—80 percent of the total—it is possible that this natural immune response was powerful enough to control the cancer completely. Rosen expects this research to spur additional studies into possible connections between cancer and other autoimmune diseases, including lupus and myositis. “It takes years to make discoveries,” he says, “but moments of intensity and asking the right questions can lead to meaningful findings.”
“Antony’s huge discovery has affected science around the world,” says Sanjay Desai, director of the Osler Medical Training Program. Desai also recognizes Rosen’s positive impact on Johns Hopkins trainees.
Laura Cappelli fondly recalls her first interaction with Rosen during her Osler training. Then her attending physician, he encouraged Cappelli to extract fluid from a patient’s knee; afterward, Rosen praised her skill. “Despite his remarkable accomplishments, he’s never arrogant,” she adds, “and has something compelling to say about every subject.”
For Cappelli and others pursuing careers in academic medicine, today’s flattened research funding can be discouraging. Rosen, however, says he’s hopeful, “as long as we stay creative, take advantage of novel opportunities and create venues that pull people from different disciplines together to talk about important, basic problems in human disease and biology.”
To hear Rosen’s lecture, “Autoimmunity in Rheumatic Diseases: New Insights” visit http://tinyurl.com/ka5adsk.