NIH Distinguished Investigator Warren J. Leonard, M.D., has spent more than 30 years conducting pioneering research into the immune system, the network of cells and other structures that help protect the body against disease. His research has focused on hormones of the immune system known as cytokines. Among his many contributions to the field is his discovery of the genetic mutations that cause X-linked severe combined immunodeficiency (XSCID), also known as the “Bubble Boy” disease, a rare genetic disease made famous by a boy who lived for 12 years in a plastic, germ-free shelter to avoid infections. Dr. Leonard found that this form of SCID and three others are diseases of defective cytokine signaling.
Dr. Leonard, chief of the Laboratory of Molecular Immunology and director of the Immunology Center at the National Heart, Lung, and Blood Institute (NHLBI), is now being recognized for his achievements with one of science’s top honors: election to the National Academy of Sciences. He is among 84 new members elected to the Academy in 2015.
“Election to the National Academy of Sciences is one of the greatest honors bestowed upon a scientist,” said Dr. Gary Gibbons, director of NHLBI. “The NHLBI community joins together in offering Dr. Leonard congratulations on being elected to this esteemed group of individuals.”
As noted, Dr. Leonard’s laboratory focuses on cytokines, small proteins that are released by cells and induce new signals in immune responses, including signals in inflammation, allergy, infection, and cancer. His lab focuses on a particular family of cytokines that includes many that are called interleukins.
Early in his career, Dr. Leonard became the first to clone and characterize a component of the human receptor for the cytokine, interleukin-2 (IL-2), which plays a key role in regulating immune responses. His groundbreaking research in this area eventually led to his discovery that mutation of a component of the receptor for IL-2 is mutated in patients with the so-called “Bubble Boy” disease. This led to his discovery that this same receptor component is shared by a family of cytokines, which in turn led to the discovery of the basis for additional forms of SCID. One of these was due to mutations in a kinase called JAK3, which led Dr. Leonard to predict that agents that inhibit JAK3 might be immunosuppressive.
Dr. Leonard’s studies of cytokines and their receptors have led to new insights into the requirements for the evolution of a wide range of other immune-related diseases including rheumatoid arthritis, type 1 diabetes, lupus, asthma, and other conditions. Likewise, his findings have provided the research community with potential targets to explore in finding treatments for these conditions. Moreover, he has also contributed to our understanding of the ability of these cytokines to exert anti-cancer effects. Furthermore, he has made major contributions to our understanding, including in a genome-wide fashion, of the actions of cytokines on gene regulation and epigenetics and mechanisms underlying T cell differentiation.
In 2015, Dr. Leonard’s team co-led a multi-institutional research effort to develop a new way to modify interleukin-2 (IL-2), a cytokine that plays key roles in regulating immune system responses, in order to fine-tune its actions. Harnessing the action of IL-2 in a controllable fashion is of clinical interest with potential benefit in a range of conditions, including transplantation and autoimmune disease. The modified IL-2 molecules inhibited the actions of endogenously (internally) produced IL-2, potentially more effectively than existing agents. The modified IL-2 molecules also inhibited the actions of another interleukin, IL-15, a finding which might also provide disease-fighting benefits, the researchers suggest.
Dr. Leonard received his bachelor’s degree in mathematics, magna cum laude and Phi Beta Kappa, from Princeton University in 1973 and his M.D. from Stanford University in 1977. After completing residency training in medicine at Barnes Hospital in St. Louis, and a year of research in biochemistry at Washington University in St. Louis, he came to the NIH as a postdoctoral fellow in the Metabolism Branch, National Cancer Institute, in 1981. He began directing his own laboratory in the Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, in 1985 and then joined the NHLBI in 1992.
In addition to membership in the National Academy of Sciences, Dr. Leonard is the recipient of many other honors and awards, including the American Federation for Clinical Research Foundation Outstanding Investigator Award, the Food and Drug Administration Center for Biologics Evaluation and Research Outstanding Service Award, the American Association of Immunologists (AAI)-Huang Foundation Meritorious Career Award, and the Honorary Lifetime Membership Award of the International Cytokine and Interferon Society. Dr. Leonard is also a Fellow of the American Association for the Advancement of Science (AAAS) and a member of the Institute of Medicine (IOM) of the National Academies.
The NHLBI scientist has authored or coauthored more than 300 articles and book chapters and holds 19 patents. He is currently an Associate Editor and former Co-Editor of Immunity, on the editorial board of Cytokine, an Associate Editor of International Immunology, and a contributing member of the Faculty of 1000. Moreover, he is past-president of the International Cytokine Society, a member of the Board and former vice president of the Foundation for Advanced Education in the Sciences (FAES), a member of the American Association of Immunologists, the American Society for Clinical Investigation, and the Association of American Physicians.
The National Academy of Sciences was established by an Act of Congress in 1863 to provide scientific advice to the government “whenever called upon” to do so by any department of the Government. The organization now includes the National Research Council, the National Academy of Engineering, and the Institute of Medicine — known collectively as The National Academies. The organization, which includes some of the Nation’s top scientists, engineers, health professionals, and other experts, has produced reports that have led to some of the most important advances in health, education, and welfare in the world.