Several laboratories at the La Jolla Institute for Allergy & Immunology are researching inflammation biology. Researchers at the Institute have made great strides with three particular diseases including Coronary Artery Disease, Lung Disease and Sickle Cell Disease. Our research laboratories study the body's inflammatory response in each disease and are working toward discovering the pathways that lead to the treatment and prevention of these diseases.

BREAKTHROUGHS

Identification of Four Candidate Biomarkers for Aortic Aneurysms
An abdominal aortic aneurysm (known as AAA) is a result of complications from atherosclerosis. An AAA is a weakness in the abdominal aorta that causes dilation or a bulging out in a portion of the artery. If the bulge ruptures, you can die. Out of hundreds of biomarkers for the disease that causes this abdominal aortic aneurysm, or bulge, Dr. Klaus Ley has identified four candidate biomarkers for the disease.  Dr. Ley's inflammation research is essential to the ultimate creation of a test for AAA that is as good as or better than PSA (prostate-specific antigen) is for prostate cancer. This would save lives by making diagnosis more available and affordable.

Drug in Clinical Trials for Sickle Cell Anemia
At the La Jolla Institute, Joel Linden, Ph.D. is making strides in the pursuit of new treatments for sickle cell disease. Linden is an expert in adenosine receptors, which are proteins on the surface of cells that recognize certain molecules that reach the cell surface and trigger a response. "We believe that activating adenosine receptors to inhibit inflammation has a lot of potential uses in inflammatory diseases such as sickle cell disease," said Linden. In particular, Linden found that when a person with sickle cell disease has blocked blood flow due to red cell sickling, and then restoration of blood flow (called ischemia reperfusion injury), certain immune cells get activated, especially natural killer t-cells (NKT). Basically what happens is the body inappropriately responds to the event by sending out immune cells to kill what it thinks is an infection or foreign invader. But over time, the NKT cells can damage the organs and tissues, shortening the life span of sufferers. Linden hopes that his research in adenosine could be used to block this immune response in sickle cell disease patients, in that many of the anti-inflammatory effects of adenosine are actually due to their ability to inhibit NKT cells. Linden's lab is in pursuit of two new treatments for sickle cell disease, with one already in clinical trials. "Very little progress has been made in treating this devastating disease for several decades. I think our new approach has great promise" said Linden.

ARDS and the Role of Selectins in Inhibiting the Inflammatory Response
Dr. Klaus Ley is studying the immune response that happens as a result of inflammation caused by a lung injury. Acute Lung Injury (ALI), also known as Acute Respiratory Distress Syndrome (ARDS), can happen to anyone following a traumatic blow to the lungs, or even merely aspirating gastric content. While not immediately obvious, the individual will suddenly experience complications in breathing resulting in death. Imagine the motorcycle rider who crashes his bike, causing him to sustain an acute lung injury.  Or perhaps the college student, having a wild night out with friends, goes on a drinking binge and passes out.  While the student is passed out, they aspirate gastric content, causing it to flow the wrong way into the lungs. 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 Ley.  Ley has found that in mice, they can block an immune response molecule called P-selectin, or thromboxane A2, a lipid partly responsible for clot formation.  "Preclinical studies point to practical therapies for the inflammation involved in ALI and ARDS" said Ley. "This can hit young healthy people and they can die.  If we can control the inflammatory response, we may give those with Acute Lung Injury a chance to live," said Ley.

RESEARCHERS AND THEIR LABS

Catherine C. "Lynn" Hedrick, Ph.D. studies how immune cells influence cardiovascular complications of diabetes, particularly atherosclerosis. Patients with diabetes have increased risk of developing cardiovascular disease, and Dr Hedrick's laboratory focuses on how the diabetic environment contributes to early atherosclerotic plaque development. Specifically, her laboratory studies how elevated glucose and hyperlipidemia modulate immune cell function in the vessel wall.

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.

Joel Linden, Ph.D. studies adenosine receptors which are the proteins on the surface of cells that recognize adenosine and related compounds - which is important for regulating inflammation.  Dr. Linden is interested in adenosine's affect on disease processes.  He found that the adenosine receptor is a very powerful negative regulator of many cells of he immune system.  This is important to disease because by activating adenosine respetors, inflammatory processes can be inhibited.  Inflammation has been recognized to play an important role in many diseases, and this discovery opens up numerous new potential treatments for heart failure, diabetes, Crohn's disease, and sickle cell disease.