The successful dedication of the Type 1 Diabetes Center as a comprehensive biomedical research center is due to our visionary leadership, our central location key for collaboraive partnerships, our dynamic, state-of-the-art laboratories, and dedicated people at all levels of the Institute's operation.  Most notable are the esteemed Faculty and researchers who are commited to integrating basic research and clinical care into a focused center to fight this disease and help those who suffer from it in San Diego and throughout southern California.

DIRECTOR

Matthias von Herrath, M.D.
The Center is led by Matthias von Herrath, M.D., one of the world's top type 1 diabetes researchers and recipient of the American Diabetes Association's prestigious 2008 Outstanding Scientific Achievement Award, the Center will accelerate research toward new therapies to better treat, prevent or cure type 1 diabetes.  "Our mission is to be a premier center of immunological excellence in type 1 diabetes research," said Dr. von Herrath.  The Center will focus on new, immune-based approaches and is the first such immunologically focused research center for type 1 diabetes in Southern California.  Dr. von Herrath said collaboration with local organizations is key to the Center's efforts to combat type 1 diabetes.

FACULTY

Nunzio Bottini, M.D., Ph.D.
Research in the Bottini lab is focused on a protein called PTPN22, which is a critical negative regulator of T lymphocyte activation. Dr. Bottini discovered that a mutation in the PTPN22 gene is a predisposing factor to T1D in humans. This finding was then confirmed by many groups and currently PTPN22 is ranked as a major T1D gene. Dr. Bottini's laboratory at the LIAI T1D Center is entirely focused on understanding the regulation of PTPN22 and how the T1D-predisposing PTPN22 variant alters immune cell responses in a manner that predisposes to the autoimmune destruction of insulin-producing beta-cells. The laboratory recently discovered that the T1D-predisposing PTPN22 variant shows higher function than normal. This result suggests that pharmacological inhibition of PTPN22 might be beneficial for prevention or treatment of T1D. In collaboration with other groups at the Center, the laboratory has an active translational program focused on identification of chemical and DNA-based inhibitors of PTPN22 and on testing of these early drugs in animal models of T1D. 

Hilde Cheroutre, Ph.D.
Dr. Cheroutre's Type I Diabetes research focuses on the hypothesis that defects during the initial development and "education" of immune cells (T cells), might be a major underlying cause of defective central self-tolerance leading to autoimmune Type I diabetes.  We aim at identifying the key players in this self-tolerance process and the defects that may lead to susceptibility to Type I diabetes. This will allow us to early identify and treat those individuals that might be at high risk for the development of Type I diabetes.

Lynn Hedrick, Ph.D.
Patients with type 1 diabetes develop severe vascular complications, including heart disease, arterial disease, and retinopathy.   In addition, patients with type 1 diabetes have a much higher chance of developing these vascular complications than patients who do not have diabetes.  Dr. Hedrick's research focuses on identifying and understanding the early changes that occur in blood vessels in patients with type 1 diabetes that leads to the acceleration of vascular disease.  We have identified a protein called ABCG1, which is important in regulating cholesterol content in the vascular wall, whose expression is changed in patients with type 1 diabetes.  Patients with Type 1 (and Type 2) diabetes have dramatically reduced expression of this protein.  Since this protein regulates cholesterol removal from cells in the vascular wall, patients who have less of this protein may have increased cholesterol accumulation in the artery, which leads to accelerated atherosclerotic plaque formation and heart disease.  Importantly, we have recently discovered that expression of ABCG1 is critical for insulin secretion from beta cells in islets.  If ABCG1 levels are low in the beta cell, the beta cell has impaired insulin secretion.  Polymorphisms exist in the ABCG1 gene in patients with diabetes that impact ABCG1 expression.  These ABCG1 polymorphisms have been associated with plasma insulin levels in patients with diabetes, again suggesting that ABCG1 plays an important role in regulation of insulin secretion.  Therapies to increase ABCG1 expression and function in patients with Type 1 diabetes may be important both for improving islet function as well as for reducing the vascular complications associated with Type 1 diabetes.

Klaus Ley, M.D.
T1D is an autoimmune disease where immune cells enter the pancreas and destroy the cells that make insulin. Dr. Ley's lab have tried to inhibit the migration of these immune cells by locking them up in lymph nodes and the spleen. This works quite well and can completely prevent T1D in a mouse model. But would it work as a therapy? Probably not. When mice were made diabetic and started on the drug right then, the mice were fine and did not become diabetic. But when the drug was withdrawn after a few weeks, they all became diabetic. When the treatment was started after the disease had fully developed, it did not work any longer and the mice stayed diabetic. 

Yun-Cai Liu, Ph.D.
The immune system has evolved to mount robust responses against invading pathogens, but at the same time, is tolerant to self-tissues or self-antigens. The study of immune tolerance has been a central topic in the field of immunology for quite a long time, since failure in or breakdown of immune tolerance results in disastrous consequences like the development of autoimmune diseases including type 1 diabetes. T cells are the critical components of the immune system, which function via specifically recognizing the antigenic peptides presented by the antigen-presenting cells and orchestrating effective immune responses. The T cell tolerance to self-antigen is generated through both central and peripheral mechanisms, which starts at the developmental stage in thymus, and continues to keep T cell under control in the peripheral via ignorance, deletion, anergy, or the production of T regulatory cells. However, the exact relationship between T cell tolerance and autoimmunity remains largely unclear. Our laboratory is studying the process of tagging a small molecule ubiquitin to a protein substrate and the subsequent consequences of such modification in T cell activation and tolerance induction. Particularly, we are using the NOD mouse model of type 1 diabetes to investigate the molecular mechanisms of ubiquitin conjugation in the immune regulation and diabetes development. The expected information may help in the design of therapeutic inventions for human type 1 diabetes.

Anjana Rao, Ph.D.

Stephen Schoenberger, Ph.D.
A central focus of Dr. Schoenberger's research is the regulation of CD8+ T lymphocytes (CTL), which carry out the task of killing the body's own cells should they become infected or otherwise compromised. In diabetes, it is believed that CTL mistakenly target and destroy normal insulin-producing cells in the pancreas, and it is this step that his research aims to prevent. Dr. Schoenberger's lab has identified a key molecular interaction that mediates the death of activated CTL under normal circumstances, and has shown that monoclonal antibodies against a specific receptor can be used to selectively eradicate CTL that recognize the normal insulin-producing cells in an animal model of Type I diabetes. Current efforts are focused on understanding the mechanism underlying this effect, and performing translational studies to move this approach to the clinic.