School Notes: School of Medicine
July/August 2010

Zeroing in on genes to head off aneurysms

In a new genomic study, a team led by Yale researchers has identified three new regions of the genome containing variants that increase the risk of intracranial aneurysms—weaknesses in the brain’s blood vessels. Brain aneurysms rupture in 500,000 people worldwide each year, causing hemorrhagic stroke, but most people have no prior symptoms. Rupture is fatal in up to 40 percent of cases, and survivors usually have severe neurological damage. The team compared nearly 900,000 variable spots in the genomes of 6,000 aneurysm patients with those of 14,000 healthy subjects. In the May issue of Nature Genetics, they describe the new regions and confirm that two previously identified loci are strongly associated with aneurysms. The new knowledge is “ten percent more than we understood just a couple of years ago,” says lead author Murat Günel ’94Grd, the Nixdorff-German Professor of Neurosurgery.

An engineered tissue’s surprising development

Christopher K. Breuer and Toshiharu Shinoka, both associate professors of surgery and pediatrics, have been studying the use of tissue-engineered vascular grafts (TEVGs) to treat congenital heart defects. TEVGs—created from a patient’s bone marrow cells (BMCs)—make living vessels that will grow as a child grows and could last a lifetime. With colleagues, Breuer and Shinoka explored how BMCs are transformed into vessels in TEVGs. Many scientists thought that BMCs—stem cells—differentiate into several kinds of cells that make up blood vessels. But the group found that BMCs were undetectable soon after TEVGs were implanted into mice. Instead, the graft appeared to initiate an inflammatory response that drew white blood cells to the scaffold, replacing the BMCs. These cells were also soon replaced—with the mouse’s own blood vessel cells. This “better understanding of how TEVGs develop in vivo will lead to improved second-generation TEVGs,” the authors write in Proceedings of the National Academy of Sciences.

Autoimmunity expert named Beeson Professor

Joseph E. Craft, chief of the section of rheumatology and director of the Yale Investigative Medicine Program, as well as chief of rheumatology at Yale–New Haven Hospital, has been named the Paul B. Beeson Professor of Medicine. Craft is an internationally recognized expert on the pathogenesis of systemic autoimmune diseases, including lupus and rheumatoid arthritis. He and his research team seek to define the mechanisms of loss of self-tolerance and activation of autoreactive T cells in systemic autoimmune diseases, as well as the differentiation and regulation of T cells in normal immune responses. The Beeson professorship was established in 1981 by the late Elisha Atkins to honor his colleague, Paul B. Beeson, chair of Yale’s Department of Internal Medicine from 1952 to 1965.