Prominent immunologist and leader in diabetes research joins UCSF study

By Wallace Ravven

Jeffrey A. Bluestone, PhD, one of the world’s leading experts on why the body’s
immune system rejects or tolerates transplanted tissue, has been appointed to a
new professorship at the University of California, San Francisco devoted to
diabetes research.

Bluestone is recognized internationally for his contributions toward clarifying
the biological basis of immune tolerance. He is perhaps best known for
molecular-level approaches to control the immune activity of antibodies and
boost the beneficial effects of tolerance-inducing drugs. This research has
stimulated recent progress in islet cell transplantation for treating Type 1

He will head up the UCSF Diabetes Center, one of only a few diabetes programs
nationwide to combine the best available patient care and education with
aggressive basic research on the causes of and potential cures for the disease.
For example, efforts are under way at UCSF to understand how islet cells—the
insulin factories in the pancreas—develop and to understand why these cells
become targets for destruction by the immune system.

Bluestone’s appointment is expected to strengthen and accelerate research on
diabetes and other autoimmune diseases at UCSF and quicken the pace of applying
promising new research findings to clinical treatments. The aim is to improve
the success of transplantation and of newer, less invasive treatments for
diabetes and other autoimmune diseases, allergies and asthma.

Bluestone will hold the new A.W. & Mary Margaret Clausen Distinguished
Professor in Metabolism and Endocrinology at UCSF and has also been appointed
director of UCSF’s Hormone Research Institute and the Metabolic Research Unit.

“Jeff Bluestone is a spectacular addition to an already formidable immunology
program, ” said Haile T. Debas, MD, dean of the School of Medicine at UCSF. “We
expect our diabetes program, in both basic research and patient therapies, to
become a national leader.”

Bluestone comes to UCSF from the University of Chicago, where he spearheaded
the formation of an international network of more than 70 leading researchers
in nine countries, funded by the National Institute of Allergy and Infectious
Diseases (NIAID), the Juvenile Diabetes Foundation and the National Institute
of Diabetes and Digestive and Kidney Diseases to coordinate clinical testing of
new therapies to induce immune tolerance.

Among the eight clinical trials initiated during the first year by this Immune
Tolerance Network (ITN), a clinical trial is under way to replicate the
promising recent success of islet transplantation for Type 1 diabetics recently
reported by researchers in Edmonton, Canada.

The network, which has received more than $140 million in support to date, will
be based at UCSF.

In his own research, Bluestone has helped define the critical importance of
dual-signaling in the immune system—known as the T cell receptor and
co-stimulatory signaling systems—which are required to fully launch immune
rejection of organ grafts and autoimmune diseases. He has carried out animal
studies of islet transplantation using drugs that target one or the other of
the signaling mechanisms. The research indicates that a combination of drugs
could allow for successful islet transplantation without shutting down the
entire immune system. 

About one million people in the U.S. have Type 1, insulin-dependent diabetes
(formerly known as juvenile-onset diabetes), a condition in which they are
unable to produce insulin, usually because their immune system destroys the
insulin-producing pancreatic islet cells. Current treatment relies on daily
administration of insulin to regulate the body’s sugar levels. However, insulin
treatment is still inexact, and the inability to effectively control high sugar
levels can lead to devastating long-term complications.

A major goal in treatment of Type 1 diabetes has been to replace the insulin
producing islet cells. Historically, this has been done by full-organ
transplantation of a pancreas, requiring major surgery and the use of toxic
drugs to prevent graft rejection. Many researchers now hope that the use of far
less invasive islet cell transplantation, combined with the novel drugs to
induce tolerance, will lead to long-term independence from insulin treatments
for people with the disease.