Gene Mutation “Hotspots” Linked to Better Breast Cancer Outcomes

Genetic phenomenon associated with low tumor invasiveness and longer patient survival could inform prognosis and help identify patients who would best respond to immunotherapy and other treatments —

Kataegis is a recently discovered phenomenon in which multiple mutations cluster in a few hotspots in a genome. The anomaly was previously found in some cancers, but it has been unclear what role kataegis plays in tumor development and patient outcomes. Using a database of human tumor genomic data, researchers at the University of California San Diego School of Medicine and Moores Cancer Center have discovered that kataegis is actually a positive marker in breast cancer — patients with these mutation hotspots have less invasive tumors and better prognoses. … Read the Full Story from the UC San Diego News Center


Dr. Jill Mesirov

Dr. Jill Mesirov

The study coauthors included Department of Medicine faculty researchers Pablo Tamayo, PhD, and Jill P. Mesirov, PhD. Both are Professors of Medicine in the Division of Genetics.

Read the Full Text (UC San Diego Only)

Enhancer RNAs Alter Gene Expression

New class of molecules may be key emerging “enhancer therapy”

In a pair of distinct but complementary papers, researchers at the University of California, San Diego School of Medicine and colleagues illuminate the functional importance of a relatively new class of RNA molecules. The work, published online this week in the journal Nature, suggests modulation of “enhancer-directed RNAs” or “eRNAs” could provide a new way to alter gene expression in living cells, perhaps affecting the development or pathology of many diseases. … Read the full story from the UCSD Newsroom


Christopher K. Glass

Christopher K. Glass, MD, PhD

Drs. Christopher Glass (left) and M. Geoffrey Rosenfeld (at right below) are the principal investigators of the two studies reported in Nature.

M. Geoffrey Rosenfeld, MD

M. Geoffrey Rosenfeld, MD

Christopher Glass, MD, PhD, is professor of medicine and cellular and molecular medicine. M. Geoffrey Rosenfeld is professor of medicine and biology and is a Howard Hughes Medical Institute professor.

Both are members of the Division of Endocrinology & Metabolism in the Department of Medicine.

Citations for the study reports:

Glass report:

Michael T. Y. Lam, Han Cho, Hanna P. Lesch, David Gosselin, Sven Heinz, Yumiko Tanaka-Oishi, Christopher Benner, Minna U. Kaikkonen, Aneeza S. Kim, Mika Kosaka, Cindy Y. Lee, Andy Watt, Tamar R. Grossman, Michael G. Rosenfeld, Ronald M. Evans & Christopher K. Glass.  Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription.  Nature (2013) doi:10.1038/nature12209. Published online 02 June 2013.  |   Full Text  (UCSD only)

Rosenfeld report:

Wenbo Li, Dimple Notani, Qi Ma, Bogdan Tanasa, Esperanza Nunez, Aaron Yun Chen, Daria Merkurjev, Jie Zhang, Kenneth Ohgi, Xiaoyuan Song, Soohwan Oh, Hong-Sook Kim, Christopher K. Glass & Michael G. Rosenfeld. Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature (2013) doi:10.1038/nature12210. Published online 02 June 2013.  |  Full text  (UCSD only)

More Information:

UC San Diego Cancer Researchers Target Link between Obesity and Breast Cancer Risk

July 28, 2011. A team of researchers from the University of California, San Diego School of Medicine and UC San Diego Moores Cancer Center will be participating in a cooperative agreement initiative, funded by the National Cancer Institute (NCI) of the National Institutes of Health, with four other major cancer centers. The Transdisciplinary Research on Energetics and Cancer (TREC) initiative…. Read the full story from the UCSD Newsroom

Dr. Jerrold Olefsky

Jerrold M. Olefsky, MD, is principal investigator of one of the four UC San Diego projects: Role of Inflammation and Insulin Resistance in Mouse Models of Breast Cancer. He is one of 22 researchers taking part in the UC San Diego TREC project. Dr. Olefsky is Distinguished Professor of Medicine in the Division of Endocrinology and Metabolism and Associate Dean for Scientific Affairs, UC San Diego Health Sciences. | Read the UC San Diego TREC project abstract

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.

UC San Diego Researcher Awarded $5.3 Million for Breast Cancer Survivorship Study

Dr. Barbara A. Parker is an investigator in the new clinical trial described in “UC San Diego Researcher Awarded $5.3 Million for Breast Cancer Survivorship Study” from the UCSD Newsroom.

Barbara A. Parker, M.D., Medical Director of Oncology Services for the Moores UCSD Cancer Center, is Professor of Clinical Medicine in the Division of Hematology-Oncology.

Overnight Fasting May Reduce Breast Cancer Risk in Women

A decrease in the amount of time spent eating and an increase in overnight fasting reduces glucose levels and may reduce the risk of breast cancer among women, report University of California, San Diego School of Medicine researchers in the journal Cancer Epidemiology, Biomarkers & Prevention. … Read the full story from the UC San Diego Newsroom