Dr. Yokoyama was recognized for his important discoveries on the role of natural killer (NK) cells, an interesting immune cell population that has cytotoxic activity and may play a key role in regulating the immune response as well as tumor cell killing. Specifically, Dr. Yokoyama’s research identified the Ly49A receptor, which is responsible for inhibiting NK cells, components of the immune system. The 1992 discovery, the first identification of an NK cell receptor, ultimately helped reveal how NK cells defend the body against viruses and kill certain types of tumors.
Prior to Dr. Yokoyama’s findings, scientists believed NK cells were insignificant to immunity because, unlike T and B cells, they didn’t appear to discriminate between particular pathogens or tumors.
In 2005 Dr. Yokoyama made further progress in understanding how NK cells function and what processes influence their potency. He found that NK cells work efficiently throughout life only if they are “licensed.” During licensing, Ly49A or another NK cell inhibitory receptor must bind to certain molecules in order to allow the cell to change and function properly.
His work has led to a host of other NK cell observations. Dr. Yokoyama says researchers in other labs are providing convincing evidence that NK cells may be involved in autoimmune conditions such as juvenile rheumatoid arthritis.
“I was of, course, delighted to be selected by the Arthritis Foundation’s review panel,” says Dr. Yokoyama. “It’s ironic. We didn’t set off specifically to do arthritis research.”
He explained that when he first began his current research when still a post-doc at the National Institutes of Health in the 1980s, working under physician-scientists Ethan Shevach and David Cohen, the focus was on studying the role of T cells, not NK cells. It took years of study to understand the role and function of Ly49A and to come to the realization that it had little to do with T cells and more to do with NK cells, says Dr. Yokoyama. Yet he believes unexpected discovery is the beauty of scientific research. “If you always find what you expect you will find there’s no need to do research,” he says.
Dr. Yokoyama says that his supervisors “gave me freedom to study what we wanted. We followed where the science was taking us.”
Along with treating patients, Dr. Yokoyama is a two-time Howard Hughes Medical Institute investigator; professor of medicine, pathology, and immunology; chief of the rheumatology division; and director of the Center for Arthritis and Related Diseases and the Rheumatic Diseases Core Center.
He also directs Washington University School of Medicine’s dual-degree MD-PhD, Medical Scientist Training Program. He holds deep appreciation for the value a good mentor can play in a researcher’s career, a belief acquired from personal experience. His long-term mentor is a high-school biology teacher who encouraged Dr. Yokoyama to pursue his interest in scientific research in high school and has encouraged him throughout his career.
After completing an undergraduate degree in biology at the University of Rochester, Dr. Yokoyama returned to his native Hawaii and obtained a medical degree at the University of Hawaii at Manoa. He completed a residency and a rheumatology fellowship at the University of Iowa Hospitals, in Iowa City, and a research fellowship in immunology at the National Institute of Allergy and Infectious Diseases (NIAID). He joined the Washington University School of Medicine in 1995.
He continues to make new discoveries surrounding NK cell receptors and how the innate immune system controls virus infections at his lab at Washington University.
Using Art to Teach and Inspire
During his more than 20 years of volunteerism for the foundation, Dr. Louie has inspired both physicians and patients by highlighting famous artists, past and present, who had arthritis and related diseases under the foundation’s purview.
He gives patients hope for coping with their disease by illustrating how famous artists managed, artists such as Pierre-Auguste Renoir, Henri de Toulouse-Lautrec, Raoul Dufy, Grandma Moses, and Paul Klee, all of whom had a form of arthritis. Some of the artists were able to manage their disease through the grit of their own determination, the support of family and friends, and by using the best medical advice and therapies available during their lives. Many used their art to express their pain and turmoil, while others preferred to ignore and surpass their pain and deformities through their art.
Dr. Louie enjoys describing John Outterbridge—a Los Angeles sculptor, painter, and arts administrator, who has benefited from current therapies that allow him to be fully functional—to newly diagnosed patients with rheumatoid arthritis who are worried about their condition. “Patients can identify with people who have to fight and keep going and, through the Arthritis Foundation, can learn how to access the best medical care of their generation,” says Dr. Louie. One of his many of medicine lectures, “Artists With Rheumatoid Arthritis—Then and Now,” has been given to physician and lay audiences across the country, often supported by the Arthritis Foundation. The lecture portrays the evolution of treatments available to Renoir, Dufy, and Outterbridge, who lived in different time periods.
Dr. Louie served on the Arthritis Foundation’s national board of directors from 2004 to 2010, after serving on the board of the foundation’s Southern California chapter. Currently, he enjoys facilitating the foundation’s international outreach efforts to southeast Asia, where rheumatology groups want to start their own foundations modeled after the Arthritis Foundation.
He completed his medical degree at Washington University School of Medicine, an internship in internal medicine at Johns Hopkins University in Baltimore, Md., and residencies in medicine at Johns Hopkins and the UCLA School of Medicine. He completed a fellowship in rheumatology and immunology at UCLA School of Medicine, and a sabbatical at the National Institutes of Health studying cytokine functions from monocytes.
Dr. Louie was chief of the rheumatology division at the Los Angeles County Harbor-UCLA Medical Center in Torrance, Calif., and a faculty member in the UCLA School of Medicine for 30 years. As medical affairs director at Amgen Inc. in Thousand Oaks, Calif., from 2002 to 2007, he facilitated translational and clinical studies of etanercept, one of the first biologic therapies for inflammatory arthritis.
Today he is professor emeritus of medicine at the UCLA School of Medicine, providing patient care and consults at the UCLA Center for the Health Science and West Los Angeles Veterans Administration Medical Center, and collaborating with investigators at Cedars-Sinai Medical Center, Harbor-UCLA Medical Center, and other medical centers.
Dr. Louie’s long relationship with the Arthritis Foundation began in the 1970s, when the foundation was intent on encouraging promising young physicians to choose rheumatology as a specialty, and funded many fellowships at UCLA, including Dr. Louie’s. He says that volunteering to support the foundation’s mission is one way he can give back.
Kathlyn Stone is a medical journalist based in Minnesota.
