Novel Imaging Model Helps Reveal New Therapeutic Target for Pancreatic Cancer

Antisense treatment in preclinical models shows effectiveness against deadly tumors —

Pancreatic ductal adenocarcinoma, the most common of pancreatic cancers, is extraordinarily lethal, with a 5-year survival rate of just 6 percent. Chemotherapy treatments are poorly effective, in part due to a high degree of drug-resistance to currently used regimens.

In a new study, published online June 6 in Nature, researchers at University of California San Diego School of Medicine and Moores Cancer Center, together with colleagues at Keio University, the University of Nebraska and Ionis Pharmaceuticals describe an innovative new model that not only allowed them to track drug resistance in vivo, but also revealed a new therapeutic target … Read the Full Story from the UC San Diego Newsroom


Tannishtha Reya, PhD, Professor of Medicine in the Division of Hematology-Oncology and Professor of Pharmacology, was co-principal investigator of the project.

Dr. Frederick D. Park

Dr. Frederick D. Park

Another Department of Medicine coauthor was Frederick D. Park, MD, PhD, Assistant Professor in the Division of Gastroenterology.

Dr. Seth Field Elected to the American Society for Clinical Investigation

Dr. Seth FieldSeth J. Field, MD, PhD, Associate Professor of Medicine in the Division of Endocrinology and Metabolism, has been elected to the American Society for Clinical Investigation (ASCI).

ASCI membership is a distinction that recognizes the nation’s most outstanding physician-scientists.

“Seth is a highly innovative biomedical researcher, a caring clinician, and a teacher who devotes himself to mentoring learners at all levels,” said Wolfgang Dillmann, MD, Professor and Interim Chair of the Department of Medicine, who supported Dr. Field’s nomination. “He embodies the ideals of the ASCI.”

“It has been a pleasure to watch Seth’s career take off and succeed at UCSD,” said Jerrold M. Olefsky, MD, who proposed Dr. Field’s nomination. “He’s an outstanding and incisive scientist who still manages to be an exceptional clinician and teacher.”

Dr. Olefsky is Associate Dean for Scientific Affairs and Distinguished Professor of Medicine in the Division of Endocrinology and Metabolism.

Dr. Field has earned international recognition and major extramural funding for his original research. His investigations focus on the metabolism and signaling pathways of phosphoinositides, a group of lipid signaling molecules implicated in the pathophysiology of a range of human diseases.  |  Visit his laboratory website

“His findings,” said Dr. Dillmann, “have catalyzed a major paradigm shift in our understanding of the export of proteins from the cell.”

In 2009, Dr. Field and coworkers discovered that the Golgi protein GOLPH3 binds to phosphatidylinositol-4-phosphate in the trans-Golgi membranes and connects the Golgi to F-actin via binding the unconventional myosin MYO18A. The resulting tensile force plays an important role in the secretory pathway by drawing vesicles and tubules from the Golgi. In the process, the Golgi apparatus acquires its characteristic stretched and flattened shape.

Dr. Field and colleagues reported the finding in the journal Cell in October 2009. The discovery, announced in a UC San Diego press release, earned worldwide attention.  |  Read the report in Cell (free full text)

Now, in one of many subsequent studies, Dr. Field is examining how GOLPH3 may function to cause cancer and whether there are potential therapeutic targets in the GOLPH3 pathway. GOLPH3 has been identified as a cancer gene commonly associated with human cancers, including breast cancer.

This work is supported by a 5-year, $3.8 million Era of Hope Scholar Award for Breast Cancer Research he received last year from the US Army Medical Research and Materiel Command.

Dr. Field collaborated with Judith A. Varner, PhD, and coworkers in the tumor inflammation studies reported in the June 14, 2011, issue of the journal Cancer Cell. They have identified a single point at which myeloid cells are triggered to enter cancer cells and promote tumor growth: the PI-3 kinase-gamma enzyme. The report, pinpointing what may be an important new therapeutic target for cancer treatments, was highlighted in a mini-review in the same journal.  |  Read the report in Cancer Cell (free full text)

Dr. Field has also collaborated with Dr. Ronald Evans and coworkers in the Gene Expression Laboratory at the Salk Institute for Biological Studies in defining a novel negative feedback pathway for insulin signaling. The results identify a new target area for the development of insulin-sensitizing drugs.

In 2008, Dr. Field was honored with an NIH Director’s New Innovator Award, a five-year, $ 2.3-million research grant. Recipients of the NIH Director’s New Innovator Award are selected for the exceptional creativity and potential impact of their research.

In an earlier honor that brought major funding, the Burroughs Wellcome Fund granted Dr. Field a Career Award in the Biomedical Sciences in 2004. The five-year, $500,000 career awards are given to support outstanding postdoctoral researchers in their transition from advanced training to academic faculty service. The funding supported Dr. Field’s project, “Comprehensive analysis of phosphoinositide function.”

An active teacher in the Department of Medicine’s education programs, Dr. Field is also a member of the teaching and research faculty of the UC San Diego Biomedical Sciences Graduate Program. In addition, he is an investigator in the Cancer Biology program at the UC San Diego Moores Cancer Center.

Dr. Field received his MD degree from Harvard Medical School and his PhD in Genetics in the laboratory of Michael E. Greenberg, PhD, at Harvard. After his internship and residency in internal medicine at the Hospital of the University of Pennsylvania, he completed his fellowship in endocrinology at the Massachusetts General Hospital.

He returned to Harvard for his postdoctoral research training in cell biology and systems biology in the laboratory of Lewis C. Cantley, PhD. In 2005, he joined the UC San Diego Department of Medicine faculty as an assistant professor in the Division of Endocrinology and Metabolism.

Dr. Field and the other honorees for 2011, including Dr. Maike Sander from UC San Diego’s Department of Pediatrics, were introduced April 16 at the annual joint meeting of the ASCI and the Association of American Physicians in Chicago.

With the addition of Dr. Field, the ASCI now includes 63 current members of the faculty of the Department of Medicine.