Pancreatic Program Pushes Research Frontiers

L-cell in a human intestine, shown in a fluorescence microscopy image. The hormone glucagon-like peptide 1, stained green in the basal part of the cell, has a beneficial effect on metabolism.

The pancreas is not an organ that you normally notice. Located near the stomach, this unobtrusive gland goes about its business of producing insulin and other substances to help the body digest food. But when it malfunctions, it can wreak havoc.

More than 40,000 people in the U.S. each year learn they have pancreatic cancer, and the rate is rising, according to the National Cancer Institute. Over 90 percent of these patients will succumb to the devastating disease within five years, statistics indicate. While this cancer is associated with a number of risk factors, including diabetes, obesity and smoking, the cause is mysterious.

Another pancreatic disorder, acute pancreatitis — or inflammation of the pancreas — is among the most frequent gastrointestinal causes of hospital admission. It is painful and can be life-threatening.

Enter the new Cedars-Sinai Pancreatic Diseases Program. Now in its second year, it enlists teams of scientists and clinicians in a collaborative drive to understand, prevent, diagnose and treat pancreatic disorders. Under the direction of Stephen J. Pandol, MD, director of basic and translational pancreatic research in the Department of Medicine, this multidisciplinary program currently coordinates more than a dozen research studies.

"Our first year was our thinking year — to get all our ideas together," Pandol said. "Going forward, we expect to refine our working teams and their projects."

Cedars-Sinai is well-suited to such joint efforts. "Normally, there's a chasm between people who see patients and people who work in the laboratories," Pandol explained. "We are talking different languages." But Cedars-Sinai, in pursuing its dual mission as a medical and academic center, fosters cooperation across departments, he said.

For instance, Pandol said, a conversation with Marc Troup Goodman, PhD, director of cancer prevention and genetics and associate director of population science at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, opened up a new avenue of research for the pancreatic program.

"I was talking with him about risk factors for pancreatic cancer," Pandol recalled, when Goodman mentioned that gastric bypass surgery, a treatment for severe obesity, also resolves adult-onset, or type 2, diabetes. Intrigued, the two men hypothesized that the surgery, by creating a new connection between the stomach and small intestine, alters the gut's bacterial environment in a way that counters diabetes. They have proposed a pilot study, drawing on patients from the Cedars-Sinai Weight Loss Center, to test this theory.

A related project is led by co-investigators Pandol and Ravinder Abrol, PhD, a computational molecular biologist at the Cedars-Sinai Digestive Diseases Center who also is a faculty member in the Departments of Medicine and Biomedical Sciences. Along with colleagues, they are studying special cells, known as L-cells, that line the intestinal tract. These cells release hormones — glucagon-like peptide 1 and peptide YY —that have a beneficial effect on metabolism.

The scientists are seeking to discover unique sensors in these cells that regulate the hormone releases and, they believe, likely are responsible for the resolution of diabetes after gastric bypass surgery. Potentially, therapies that focus on these sensors may reduce or prevent diabetes, removing a risk factor for pancreatic cancer.

The L-cell research relies on molecular structure modeling of gastrointestinal receptors and patient tissue samples from the Cedars-Sinai Biobank. This extensive tissue repository, overseen by Beatrice Knudsen, MD, PhD, is "critical" to the success of the study, Pandol said.

Stephen J. Pandol, MD

Other teams in the pancreatic program are investigating, among other topics: the role of alcohol abuse in pancreatitis and the cellular supporting structures in pancreatic cancer; how the pancreas protects itself from injury; the usefulness of MRI brain mapping in diagnosing pancreatitis; and how to achieve early diagnosis of pancreatic cancer.

Pandol's vision for his program is wide-ranging, with an eye to leveraging Cedars-Sinai's extensive facilities, patient base and faculty and physician roster to create a world-class center for pancreatic research and creation of important treatments.

"My goal is to have clinicians and researchers working together upfront to design the whole pathway — from developing models of the disease, to preclinical investigations to develop new therapies, to developing clinical trials," he said.

For more information about the Pancreatic Diseases Program, please contact Pandol at