Keichi Itakura, Ph.D., Arthur Riggs, Ph.D., David V. Goeddel, Ph.D. and Roberto Crea, Ph.D.

‘Hidden History’: Legacy of Diabetes Research at City of Hope

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Arthur Riggs, Ph.D.

City of Hope’s Arthur Riggs Diabetes & Metabolism Research Institute is committed to developing a cure for type 1 diabetes, fueled by a $50 million funding program led by the Wanek family.

But it's natural to wonder: Why would a cancer center be the recipient of such a transformative gift? Believe it or not, City of Hope — widely known as a center for cancer care and research — is the home of one of the most influential diabetes research programs in the world.

“There is a hidden history of diabetes at City of Hope that needs to be told,” said Fouad Kandeel, M.D., Ph.D., chair of the departments of Translational Research and Cellular Therapeutics, and Diabetes, Endocrinology & Metabolism, director of the Islet Cell Transplant Program and associate director of the Arthur Riggs Diabetes & Metabolism Research Institute at City of Hope. “We’re a powerhouse that is not as well-known as we should be.”

breakthroughs - world diabetes day II
Fouad Kandeel, M.D., Ph.D.

According to Arthur Riggs, Ph.D., the Samuel Rahbar Chair in Diabetes & Drug Discovery, director of the Diabetes & Metabolism Research Institute at City of Hope and director emeritus of Beckman Research Institute of City of Hope, the organization has been a major player in diabetes research since it first established a Division of Diabetes in the early 1970s.

He should know — back in 1978, Riggs, along with Keiichi Itakura, Ph.D., professor in the Department of Molecular and Cellular Biology, conducted research that led to the development of synthetic human insulin.

“We’ve made tremendous advances in the field of diabetes research, starting with the work of Rachmiel Levine,” said Riggs.

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Arthur Riggs, Ph.D., and Keiichi Itakura, Ph.D., in 1978

The late Levine, a physician and former executive medical director at City of Hope “wrote the book” on diabetes and glucose uptake, Riggs said. In fact, he was dubbed the "Father of Modern Diabetes Research" after discovering the role of insulin in glucose metabolism in 1949. Levine came to City of Hope just in time to encourage the work of Riggs and Itakura, which led to the development of the first genetically engineered health care product — Humulin — approved by the Food and Drug Administration. Today, the medication has become the standard of care for diabetes, helping over 4 million people worldwide.

In 1982, Yoko Fujita-Yamaguchi, Ph.D., professor emeritus of the Arthur Riggs Diabetes & Metabolism Research Institute of City of Hope and adjunct professor of molecular and cellular biology, isolated specific cell proteins that interact with insulin and mediate its metabolic effects, increasing scientific understanding of how insulin work in cells.

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Rama Natarajan, Ph.D.

In the early 1990s, Rama Natarajan, Ph.D., now the National Business Products Industry Professor in Diabetes Research and professor and chair of the Department of Diabetes Complications and Metabolism, conducted seminal research dealing with diabetic complications and islet dysfunction, which has led to the identification of novel therapeutic targets and agents for the treatment of such complications.

Natarajan was also the first to demonstrate the role of epigenetics in diabetic vascular inflammation and in the metabolic memory phenomenon. Her work continues to explore the role of epigenetics, or the changes that are made to our genes by external or environmental factors, in diabetes. Later that decade, Barry Forman, M.D., Ph.D., identified molecules that promote fat cell formation and affect insulin resistance in patients with type 2 diabetes.

By the turn of the new century, City of Hope had established the Southern California Islet Consortium, which serves as a central resource to prepare and distribute islets (insulin-making clusters of cells) for transplantation and research. In 2004, Kandeel led the first islet cell transplantation at City of Hope, a technique that replaces islet cells destroyed by type 1 diabetes with healthy ones. Since then, he has perfected clinical islet cell transplantation protocols and has developed imaging methods that enable physicians to monitor in real time the health of islets after transplantation.

In 2014, City of Hope established the Diabetes & Metabolic Research Institute, integrating basic, translational and clinical research with innovative care and comprehensive education. The work done there has resulted in exciting developments in cell transplantation, gene regulation and immune tolerance, and in gaining systemic understanding of diabetes as a complex, multifaceted disease. Current projects are taking a closer look at the cancer-diabetes connection, using high-tech analytic tools to revolutionize the way diabetes is treated, developing vaccines that could result in a cure and addressing the complications that often result in increased morbidity for patients, among many other research initiatives.

Then, in 2017, came the Wanek gift. Through the generosity of the family and gifts from an anonymous donor, City of Hope will be able to devote more than $50 million over the next six years to an unprecedented research effort: The Wanek Family Project for Type 1 Diabetes at City of Hope. The ultimate prize — a cure for type 1 diabetes — might be just around the corner.

Not too shabby for a program that’s just 46 years young.

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