La Jolla Institute for Allergy and Immunology (LJI, previously LIAI) is dedicated to understanding the intricacies and power of the immune system to that we may apply that knowledge to promote human health and prevent a wide range of diseases. Since its founding in 1988 as an independent, non-profit research organization, the Institute has made numerous advances leading towards its goal: Life Without Disease.
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Center for Infectious Disease
The La Jolla Institute for Allergy & Immunology launched the Center for Infectious Disease in 2006, focusing research efforts on new and re-emerging infectious diseases such as West Nile virus and avian influenza, along with potential bioterrorist agents such as smallpox. The Center is led by vaccine expert Alessandro Sette, Ph.D.
The development of vaccinations continues to be a major priority in research and clinical medicine. There are a large number of diseases that do not have vaccinations that are effective, as in the case of HIV and malaria. New and emerging infectious agents such as SARS and avian flu, as well as resurfacing dormant diseases, are frequently without effective treatment as well. Threats of bioterrorism are also bringing the attention of the medical research community back to diseases such as anthrax and smallpox. La Jolla Institute's research scientists are working to understand how we can better immunize ourselves against infection and how we can better combat infections once we have been exposed.
Gene discovery that triggers disease-fighting antibodies
A research team led by the La Jolla Institute for Allergy & Immunology has identified the specific gene which triggers the body to produce disease-fighting antibodies - a seminal finding that clarifies the exact molecular steps taken by the body to mount an antibody defense against viruses and other pathogens. The finding, published online in the prestigious journal Science, has important implications for aiding researchers in the development of new and more effective vaccines. The La Jolla Institute's Shane Crotty, Ph.D. was the lead scientist on the team, which also included researchers from Yale University.
Key role in biodefense
Shane Crotty, Ph.D., a principal investigator at the Institute, identified an antibody that could be the nation's first line of defense in protecting against a terrorist-sponsored smallpox outbreak. The Institute states that Dr. Crotty's work is one of several La Jolla Institute for Allergy and Immunology projects under way that play a key role in the nation's biodefense efforts. In 2005, while studying long-term immunological memory to the smallpox vaccine, Dr. Crotty identified the anti-H3 antibody in humans that quickly fights the smallpox virus. This is a vital finding since the younger portion of the U.S. population is not vaccinated (routine U.S. smallpox immunization ended in 1972). Dr. Crotty is currently analyzing how to mass-produce the antibody so it may be stockpiled nationally, along with the smallpox vaccine.
Natural killer T-cells and Lyme disease
Mitchell Kronenberg, Ph.D., found that a bacterium transmitted by a tick bite, and which causes Lyme disease, stimulates an immune attack by the NKT cells; a major discovery considering this is the first disease-causing microorganism (and only the third substance on earth) known to naturally activate NKT cells.
Immune epitope database and analysis resource (IEDB)
The Center for Infectious Disease is home to the world's largest database on how the immune system responds to infectious diseases, the Immune Epitope Database and Analysis Resource (IEDB). The IEDB is groundbreaking because it contains antibody and T cell epitope data curated from scientific literature, presented collectively to facilitate basic research. The database interface is designed to be intuitive and easily searched and to propel the dissemination of immune epitope information. The database is freely available to researchers worldwide and was created to aide in the development of new and more effective vaccines.
Allergy and asthma research
Kimishige Ishizaka, M.D., Ph.D., the Institute's first Scientific Director, received worldwide recognition in 1966 for his discovery of the IgE protein, an antibody that plays a key role in allergic disease. Today, scientists use molecular tools to unravel the remaining mysteries of allergic reactions, seeking to develop tools to treat and prevent allergies. "Ten to 20 percent of the population of industrialized countries suffers from some form of allergies," said Institute scientist Toshiaki Kawakami, M.D., Ph.D. "There is a huge need to understand this disease and to find therapeutic interventions."
Asthma accounts for one-quarter of all emergency room visits in the U.S. each year. It might come as a surprise to many that asthma results from the good intentions of the body, gone bad. Asthma can occur when T cells, the body's disease-fighting cells, respond to a stimulus and cause inflammation of the bronchial tubes, making breathing difficult. Michael Croft, Ph.D., and Institute President Mitchell Kronenberg, Ph.D., are studying ways to stop the overzealous response from the immune system's T cells, which occurs due to contact with an external allergen such as those from pollen.
OX40 Ligand in asthma
A major asthma discovery by a researcher at the Institute has been licensed by MedImmune, a biotechnology company and wholly owned subsidiary of AstraZeneca PLC. MedImmune licensed the discovery to explore its use in the development of a potential biologics drug for treating asthma. Under the agreement, MedImmune was granted exclusive intellectual property rights to the discovery, which demonstrated the pivotal role of a protein called the OX40 ligand in asthma. The finding was made by the laboratory of Institute scientist Michael Croft, Ph.D., and marked a major milestone in asthma research.
Automimmune research
Type 1 diabetes, rheumatoid arthritis, multiple sclerosis, and Crohn's disease are all examples of autoimmune diseases, which can be triggered when the body's immune system begins to attack healthy cells. Treating these diseases requires an understanding of how to turn off an immune system attack, which might seem an unusual goal. After all, most immune onslaughts are aimed at viruses, bacteria or other biological invaders to the body. But what if the immune system's attack is aimed at healthy cells, the immune 'off switch' becomes very important.
Potential new treatment for Crohn's Disease and Ulcerative Colitis
A discovery by scientists at the Institute has entered pharmaceutical research for use in the creation of a potential new antibody therapy for ulcerative colitis and Crohn's disease. The discovery of a molecule known as LIGHT was made in the laboratory of Carl Ware, Ph.D.
Institute scientist receives NIH Pioneer Award to study novel approach to autoimmune diseases
In September 2009, Institute researcher Hilde Cheroutre, Ph.D., received the 2009 National Institutes of Health Director's Pioneer Award to fund innovative research to create a new way of detecting, treating and possibly preventing autoimmune diseases, with the potential for identifying high risk for autoimmunity in newborns.
T cell activation
Ammon Altman Ph.D. has researched how T lymphocytes cells spring into action when they encounter an infected cell. This has turned up several important findings, most notably the discovery of an enzyme - protein kinase C theta - which may hold the key to controlling immune response. Better understanding of the process of T cell activation will allow scientists to design treatments aimed at either boosting an immune response, such as to fight cancer, or to suppress an unwanted immune attack on normal cells, which occurs in autoimmune disease.
Institute dedicates new Type 1 Diabetes Research Center
In 2009, the La Jolla Institute dedicated its new Type 1 Diabetes Research Center, which focuses on new immune-based approaches to type 1 diabetes. The Center is led by Matthias von Herrath, M.D., an internationally known type 1 diabetes researcher and recipient of the 2008 Outstanding Scientific Achievement award from the American Diabetes Association. Eight Institute faculty members contribute to the Center's research. In addition, Center faculty collaborate with local and national scientists to speed up efforts toward new treatments or a cure.
Moving closer to a cure for Type 1 diabetes
One of the Center's primary areas of study is on a combination therapy developed by Dr. von Herrath, which has shown significant promise in mouse models at stopping type 1 diabetes when caught in the early stages. Dr. von Herrath is hopeful that clinical trials will start on the combination therapy in the near future.
Allergies In San Diego Video
Cancer research
Cancer is the second leading cause of death in the United States today. At the Institute, researchers are working to defeat cancer by finding ways to boost the disease-fighting power of the immune system. Stephen Schoenberger, Ph.D., studies lymphomas and leukemias. He states that he sees "real possibilities" for solving the biological paradox of blood cancers.
Tumor suppressor
Institute researchers studying an enzyme believed to play a role in allergy onset, instead have discovered its previously unknown role as a tumor suppressor that may be important in myeloproliferative diseases and some types of lymphoma and leukemia. Myeloproliferative diseases are a group of disorders characterized by an overproduction of blood cells by the bone marrow and include chronic myeloid leukemia. Lymphoma and leukemia are cancers of the blood.
"PLC-beta 3 is an enzyme, but the function we found was a completely different function that no one knew it had - as a tumor suppressor," said the La Jolla Institute's Toshiaki Kawakami, M.D., Ph.D., who led the research team. The study, conducted in mouse models, could eventually lead to the development of new therapies directed towards controlling this newly discovered cellular mechanism.
Inflammation biology
Klaus Ley, M.D., studies the underlying factors that contribute to the disease atherosclerosis, and more specifically the chronic inflammatory response. His research has uncovered the role of leukocytes (cells of the immune system), and specifically the role of adhesion molecules, in the formation of these arterial plaques. Coronary artery disease, commonly referred to as coronary heart disease, atherosclerosis or ischaemic heart disease, is the result of plaques that form in the major arteries supplying blood to the heart.
Dr. Ley is also studying the immune response that happens as a result of the inflammation caused by lung injury. The first hours of the inflammation determine the progression and ultimate outcome of the disease. Dr. Ley is working on the role of selectins in inhibiting the inflammatory response in the beginning stages, thus reducing the degree of disease infiltration. "You can get away with blocking the inflammation for a few hours, which may be enough to intervene and maintain oxygen flow," said Dr. Ley.
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