Jeffrey Bluestone in his UCSF lab, where he's leading research to better understand autoimmune diseases. Photo by Susan Merrell
A $10 million gift from The Parker Foundation, founded by Silicon Valley entrepreneur and philanthropist Sean Parker, will establish a new research laboratory within the Diabetes Center at UC San Francisco devoted to understanding autoimmunity, in the hopes of laying the groundwork for new treatments for diseases ranging from type 1 diabetes to multiple sclerosis to rheumatoid arthritis.
The new center, to be known as the Sean N. Parker Autoimmune Research Laboratory at UCSF, will be headed by UCSF’s Jeffrey A. Bluestone, PhD, one of the world’s leading immunologists.
“I believe that it is critical to significantly expand our understanding of autoimmune disease mechanisms in order to accelerate the development of new therapies that improve treatments and reduce costs,” said Parker. “I’m confident that under the leadership of Dr. Bluestone, this research initiative will transform our approach to autoimmune diseases and result in improved outcomes for millions of patients.”
Rising Incidence of Autoimmune Diseases
There are more than 80 autoimmune diseases affecting between 14 and 22 million Americans, according to the National Institutes of Health (NIH), and their incidence is rising. In 2001, the director of the National Institute of Allergy and Infectious Diseases pegged the annual cost of treating all autoimmune diseases in the U.S. at $100 billion. More recently the NIH has estimated that annual medical costs for treating type 1 diabetes alone range between $4.6 and $9.2 billion; for multiple sclerosis, annual costs have been estimated at $2.5 billion; for rheumatoid arthritis, $19.3 billion; for systemic lupus erythematosis, as high as $9.6 billion.
Autoimmune diseases are devastating conditions in which the immune system, which normally detects and defends against foreign invaders such as viruses and bacteria, goes awry and attacks the body’s own tissues and organs. Although there has been intensive research into the commonalities of these otherwise diverse diseases, the underlying causes of the conditions are largely unknown, and drug development has been extremely slow.
To accelerate the development of new treatments, for the past 20 years, Bluestone has championed research based on the concept of immune tolerance to promote the discovery of novel therapies for organ transplant rejection and autoimmunity. Rather than suppressing immune function – the mode of action of many drugs for autoimmune diseases – immune tolerance therapies aim to halt, or even prevent, autoimmune diseases while preserving the disease-fighting capabilities of the immune system. Moreover, these therapies are designed to “reprogram” the immune system, with the hope that a short course of treatment will have long-lasting, perhaps lifelong, effects.
Bluestone is one of the leading immunologists in the field of T-cell activation and co-stimulation. His work has led to the development of multiple therapies that promote immune tolerance, including CTLA4Ig (Abatacept), used in the treatment of rheumatoid arthritis; the first FDA-approved drug targeting T-cell co-stimulation to treat autoimmune disease and organ transplant rejection (Belatacept); a novel anti-human-CD3 antibody being developed to treat type 1 diabetes; and the first CTLA-4 antagonist drugs approved for the treatment of metastatic cancer. His recent research has focused on the critical role of regulatory T cells (Tregs) in autoimmune diseases such as type 1 diabetes, lupus and multiple sclerosis, a role that has been exploited in cell-based therapies to treat autoimmune diseases and transplanted organ rejection.
Expanding Immunology Research
At the new Sean N. Parker Autoimmune Research Laboratory at UCSF, Bluestone and colleagues will continue this work, with a particular focus on Tregs. Members of the laboratory will study direct Treg cell-based therapies as well as drugs such as IL-2, anti-CD3 and others that shift the balance from a disease-causing immune response to one that is dynamically controlled. In addition to their relevance to autoimmune diseases, research advances from the laboratory may also open the door to new treatments for immune consequences following organ transplantation and even for non-immune diseases, such as heart disease, muscular dystrophy and obesity.
Jeffrey Bluestone working in his lab with postdoctoral fellows. Photo by Susan Merrell
“Today, no area in biomedical research is more vibrant than immunology, and those who suffer from autoimmune diseases stand to benefit,” said UCSF Chancellor Sam Hawgood, MBBS. “Sean Parker’s generous gift empowers Dr. Bluestone and colleagues to apply novel approaches to drive the development of precise, targeted therapies for a broad array of conditions related to autoimmunity.”
The launch of the new laboratory adds to UCSF’s widely recognized strengths in immunology. The UCSF graduate program in immunology is consistently ranked as one of the best in the nation, and UCSF Medical Center offers the highest quality care for autoimmune diseases such as multiple sclerosis and diabetes, as well as immune disorders such as asthma. The Diabetes Center at UCSF, which just celebrated its 15th anniversary, has been instrumental in shaping diabetes research and care, and is one of only 16 federally recognized Diabetes Research Centers in the country.
“I am grateful for the generosity and foresight of The Parker Foundation in supporting autoimmunity research,” said Bluestone, the A.W. and Mary Margaret Clausen Distinguished Professor of Metabolism and Endocrinology and director of the UCSF Hormone Research Institute. “The progress over the past two decades in our understanding of the immune dysregulation that results in autoimmunity has been extraordinary, and points us in the direction of immune regulation as a direct target for disease intervention. This gift truly inspires us to tackle the biggest challenges in immune tolerance in the autoimmunity setting and will ensure that critical advances can be achieved more rapidly in the lab and translated to new treatments for the millions around the world with these harmful conditions.”
Bluestone is an academic leader on a national and international scale. He was the founder and served for 10 years as director of the Immune Tolerance Network, the largest NIH-funded multicenter clinical immunology research program. Bluestone was Executive Vice Chancellor and Provost at UCSF at the University of California San Francisco and is a former director of the UCSF Diabetes Center. He has authored more than 400 peer-reviewed publications and has received honors for his work, including election to the American Academy of Arts and Sciences and the National Academy of Medicine. Bluestone is the recipient of both the Gerold and Kayla Grodsky Basic Science Award and the Mary Tyler Moore and S. Robert Levine Excellence in Clinical Research Award from the Juvenile Diabetes Research Foundation.
UC San Francisco is the nation's leading university exclusively focused on health. Now celebrating the 150th anniversary of its founding as a medical college, UCSF is dedicated to transforming health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy; a graduate division with world-renowned programs in the biological sciences, a preeminent biomedical research enterprise and top-tier hospitals, UCSF Medical Center and UCSF Benioff Children's Hospitals.