A researcher with Hawaiian roots is among the 72 members elected to the National Academy of Sciences this year. Selection for the academy is a prestigious honor that recognizes distinguished and continuing achievement in research and is one of the highest marks of distinction for an American scientist.
Wayne M. Yokoyama, the Sam J. Levin and Audrey Loew Levin Professor of Research in Arthritis, and professor of medicine and of pathology and immunology at Washington University in St. Louis, is internationally recognized for his research into an important component of the innate immune system that protects against viruses and tumors.
Yokoyama’s studies have helped show how various mechanisms license, restrain and unleash natural killer (NK) cells. His lab was the first to provide the molecular basis for a theory known as the “missing self” hypothesis. Prior to the discovery of NK cells, scientists had conceptualized the immune system’s method for recognizing invaders as comparable to that of police using an all-points bulletin: an alert went out that a particular invader had been seen, and immune system cells searched for and attacked that invader when they found it.
NK cells opened up a new possibility more comparable to that of a border guard. Scientists suspected NK cells were checking the molecular “credentials” of everything they encountered and could attack if the proper identification wasn’t forthcoming. In 1992, Yokoyama’s lab was the first to identify a receptor on the surface of NK cells that enabled this process.
The receptor inhibits NK cell function when it recognizes the appropriate credentials, which in this case are major histocompatibility complex (MHC) class I molecules. Normally present on the surface of cells, these molecules are often absent on tumors and virus-infected cells, allowing the NK cell to attack the abnormal cells. The paper was recently selected for The Journal of Immunology’s “Pillars of Immunology” series.
In related work, Yokoyama’s laboratory identified a cluster of genes that encode receptors that inhibit and receptors that activate NK cells. Recent studies have shown that NK cells use these receptors to specifically recognize cells infected by viruses. In a process Yokoyama calls “licensing,” the receptors also are involved in the functional development of NK cells
Yokoyama, who is also a Howard Hughes Medical Institute investigator, chief of the Division of Rheumatology, and director of the Center for Arthritis and Related Diseases, was the 2001 recipient of the Novartis Prize for Basic Research in Immunology, which is awarded only once every three years at the International Congress in Immunology.
Yokoyama was born in Wailuku, the son of the late Harry and Alice (nee Yano) Yokoyama. He credits Miles Muraoka, his biology teacher at Aiea High School, for catalyzing his interest in science. With the support of a Hawaii Heart Association Fellowship, he began his career in biomedical research at Kuakini Hospital. His studies there won him first place in the Hawaii State Science Fair in 1970. He earned his medical degree at the University of Hawaii at Manoa in 1978.
Washington University School of Medicine’s full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.