(Editor's Note: News embargo lifted at 12 noon, April 1, Pacific Daylight Time. The research paper was posted on the PNAS website April 3.)
April 1, 2013
In groundbreaking research, the team of 16 scientists led by Dr. Guodong Zhang of the Bruce Hammock laboratory, Department of Entomology and the UC Davis Comprehensive Cancer Center, discovered cytochrome P450 epoxygenase metabolites of omega-3 fatty acid DHA or epoxy docosapentaenoic acids (EDPs) block blood supply to the tumor and thus inhibit tumor growth and metastasis.
The natural EDPs were further stabilized by a drug called a soluble epoxide hydrolase inhibitor which is already under development to control pain and hypertension. The research was published April 3 in the Proceedings of the National Academy of Sciences (PNAS).
“Many human studies have shown that omega-3 fatty acids reduce the risks of cancers, but the mechanism is poorly understood,” said Zhang, a postdoctoral researcher. “Our study provides a novel mechanism by which these omega-3 lipids inhibit cancer.”
“We demonstrated that EDPs have very potent anti-cancer and anti-metastatic effects,” Zhang said. “Current anti-cancer drugs that block angiogenesis (the formation of new blood vessels to fuel tumor progression) can cause serious side effects such as hypertension. By blocking angiogenesis by a new mechanism and by widening blood vessels, EDPs could block tumor growth with reduced side effects in cancer patients.”
Co-author Hammock, a distinguished professor of entomology with a joint appointment at the UC Davis Comprehensive Cancer Center, said the research shows lots of promise. “Basically what Dr. Zhang and his collaborators found is that the epoxides of the omega 3 fatty acid DHA are strongly anti-angiogenic and block tumor growth and metastasis. He used the soluble epoxide hydrolase inhibitors to stabilize these epoxides in mice. In contrast, the epoxides of the omega 6 fatty acid ARA (arachidonate) are mildly angiogenic and encourage tumor and wound healing.”
“Thus the effects of the soluble epoxide hydrolase inhibitors have opposite effects depending on whether the background lipid mediators are omega 3 or omega 6,” Hammock said. “Assuming that humans are mice (the study involved mice), the prediction is that with some cancer drugs--particularly the ones like sorafenib and regorafenib that are potent epoxide hydrolase inhibitors as well as anti-angiogenic agents--these could be more effective with a high omega 3 and low omega 6 background.”
Said co-author and chemist Sung Hee Hwang: “This is exciting work as a chemist to be involved in; not only was there a strong team of chemists, biochemists and analytical chemists working with Guodong, but we got the chance to collaborate with the bioengineers from the Katherine Ferrara laboratory who did the imaging as well as with some top cancer researchers from UC Davis and Harvard.”
“This is an exciting step towards our full appreciation of the impact of bioactive products from the DHA metabolome,” said Charles Serhan of Harvard Medical School, an expert on omega-3 autacoids and inflammation who is the Simon Gelman Professor of Anesthesia, Periopterative and Pain Medicine, Harvard Medical School. “This (UC Davis) contribution places metabolic conversion of omega-3 DHA to epoxy DHA products pivotal in vascular mechanisms key in cancer and vascular biology. It will be exciting to watch these important findings translated to humans for new evidence based treatments for angiogenesis, tumor growth and cancer metastasis.”
Cardiologist Jonathan Lindner of the Oregon Health & Science University lauded the research.
“The study by Zhang and colleagues has uncovered a previously unrecognized anti-cancer effect of omega-3 fatty acids which are an important lipid component of diets that have been developed to prevent heart disease and cancer,” Lindner said. “The authors have demonstrated that metabolites of these lipids can act to suppress the growth of new blood vessels that are necessary to feed tumor growth. By shutting off the tumor’s blood supply, these compounds can act to dramatically slow tumor growth and prevent metastasis. The results from this suggest that new drug strategies for fighting cancer could emerge from knowledge of how the body uses nutrition to promote health.”
“Now UC Davis researchers report that the epoxides of docosahexaenoic acid do exactly the opposite by inhibiting angiogenesis, and thus decrease tumor growth and metastasis,” Fleming said. “Thus, it may now be possible to potentate the beneficial effects of sEH inhibition by supplementing therapy with dietary omega-3 fatty acids.”
Lois Smith, professor of ophthalmology at the Harvard Medical School and Boston Children’s Hospital, commented: “Fish oil (enriched in ω3 polyunsaturated fatty acids; ω3-PUFAs) has been shown to reduce the occurrence of diseases associated with abnormal vessel development such as age-related macular degeneration and retinopathy of prematurity. In this study, Zhang et al. demonstrate that epoxydocosapentaenoic acids (EDPs), the metabolites of ω3-PUFA by cytochrome P450 enzymes inhibits vessel development in tumors and suppresses tumor growth and metastasis by reducing VEGF-C production. This discovery provides a novel mechanism of ω3-PUFAs action on vessels and tumors and may lead to new therapies.”
Zhang, who focuses his research on lipid mediators on angiogenesis, tumor growth and metastasis, received his doctorate in food science from the University of Wisconsin-Madison.
Cancer, characterized by uncontrolled growth and spread of abnormal cells, can be caused by external factors such as tobacco, infectious organisms, chemicals and radiation, and by internal factors such as inherited mutations, hormones, immune conditions and mutations that occur from metabolism, according to the National Cancer Institute. Death occurs when the cancer is not controlled. Some 1.6 million new cases of cancer are expected to be diagnosed this year. Cancer, the second most common cause of death in the United States, is exceeded only by heart disease.
Other co-authors of the paper in addition to Hammock were Jun Yang, Jun-Yan Liu, King Sing Stephen Lee, Arzu Ulu, and Sung Hee Hwang, all of the UC Davis Department of Entomology and UC Davis Comprehensive Cancer Center; Lisa Mahakian, Xiaowen Hu, Katherine Ferrara, Sarah Tam, and Elizabeth Ingham, UC Davis Department of Biomedical Engineering; Hiromi Wettersten of the UC Davis Division of Nephrology, Department of Internal Medicine; Robert Weiss, Comprehensive Cancer Center, Division of Nephrology and U.S. Department of Veterans’ Affairs Medical Center, Sacramento; and Dipak Panigrahy and Mark Kieran of the Vascular Biology Program, Children’s Hospital, Harvard Medical School.
The research project received funding support from the National Institute on Environmental Health Sciences Superfund (Bruce Hammock); UC Davis Research Investments in the Sciences and Engineering (RISE) Program (Katherine Ferrara); NIH research grant (Dipak Panigrahy); Stop and Shop Pediatric Brain Tumor Fund and the C. J. Buckley Pediatric Brain Tumor Fund (Mark Kieran); and the Medical Service of the U.S. Department of Veterans’ Affairs (Robert Weiss). Hammock is a George and Judy Marcus Senior Fellow of the American Asthma Society.
Link to PNAS Paper
National Institute of Environmental Health Science (NIEHS) website
Contact:
Guodong Zhang at gdzhang@ucdavis.edu
--Kathy Keatley Garvey
Communications specialist
UC Davis Department of Entomology
(530) 754-6894
(From UC Davis News Service and Department of Entomology)
April 1, 2013
He is one of four young UC Davis faculty members selected for the award. Others are Ken Loh, assistant professor in the Department of Civil and Environmental Engineering, who received $400,000; Stephen O'Driscoll, assistant professor in the Department of Electrical and Computer Engineering, who received $400,000; and Ilias Tagkopoulos, assistant professor in the Department of Computer Science and the UC Davis Genome Center, who received $600,000. Together they received $2 million.
The NSF fund projects aimed at developing new nanomaterials, smaller medical implants, "biological circuits" and a better understanding of timing in ecosystems.
Yang is studying the importance of timing in interactions between plants, animals and their environment, specifically studying the monarch butterfly and milkweed. Species interactions change with the seasons and with different life stages, and climate change may disrupt these interactions, for example, if caterpillars emerge before food sources are available. His $600,000 award will support work that will provide new knowledge about how natural communities respond to such changes.
Yang was also recently selected as a UC Davis Hellman Fellow and will be honored at a luncheon in May of 2014. He received a $10,000 award to support his research activities investigating the timing of milkweed (Asclepias spp.) and monarch (Danaus plexippus) interactions in western North America due to climate change. His research addresses two main questions: “How has the relative timing of species interactions changed in the recent past?” and “What are the fitness consequences of phenological shifts?”
Yang's research interests include community ecology, species interactions, temporal variation, extreme events in nature, and the integration of ontogeny and phenology.
Yang earned his bachelor's degree (ecology and evolution) from Cornell University in 1999 and his doctorate from UC Davis in 2006, studying with entomology professor and ecologist Rick Karban. Yang conducted postdoctoral research at UC Santa Barbara before returning to UC Davis as a faculty member in 2009. While at UC Santa Barbara, he served as a UC President’s Postdoctoral Fellow in the Department of Ecology, Evolution and Marine Biology.
NSF's Faculty Early Career Development Program supports junior faculty who perform outstanding research, are excellent educators, and who integrate education and research in their work. The awards, known as CAREER awards, typically support both a five-year research program and a program of outreach and education in local schools and colleges.
Including these latest awards, current UC Davis faculty members have held a total of 63 NSF CAREER awards.
See UC Davis News Release by Andy Fell
--Kathy Keatley Garvey
Communications specialist
UC Davis Department of Entomology
(530) 754-6894
April 3, 2013
Katharina Ullmann of the Neal Williams lab is the host. The seminar is scheduled to be recorded for later viewing on UCTV.
“Increasing demands for food, and now fuel, have put pressure on our agricultural lands,” Gratton says. “Land use and land cover are continuing to change the way we manage our lands with significant biological and ecosystem-level consequences.”
“The ‘simplification’ of the agricultural landscape, that is the removal of natural and semi-natural areas in the landscape and the increase in monocultures of annual crops, is typically associated with a decrease in species richness and increases in crop pest abundance,” he said. “ These effects go beyond mere aesthetics. The consequences of landscape simplification are felt by growers who apply more pesticides in landscapes dominated by annual cropland. The question then, is can we balance our needs for agricultural production (both food and fuel) in a way that supports other ecosystem services on which we as humans depend?”
“I argue that understanding the relationships between landscape structure and the tradeoffs between ecosystem services will be a key a designing ‘custom’ multifunctional landscapes.”
Gratton joined the University of Wisconsin faculty in 2003. His research group works broadly in the field of landscape ecology in both agricultural and natural systems. In Wisconsin agriculture, he has been interested in understanding how beneficial insects, such as pollinators and lady beetles, utilize the landscape and carry out important functions such as pollination of crops and suppression of insect pests.
His work in agroecology has included studying insect landscape ecology and conservation in potatoes, rotational grazing, grasslands, soybeans, cranberries, apples.
Gratton has worked with growers to understand how to best manage non-crop “natural” areas in the landscape in order to enhance and conserve beneficial insects. He is also an active member of the Great Lakes Bioenergy Research Center as part of the team looking at developing sustainable bioenergy crops. He teaches courses in Insect Biological Control, Multivariate Analysis and Coastal Field Ecology.
He received his bachelor of science degree in biology from the University of Illinois in 1991 and his doctorate in entomology from UC Berkeley in 1997.
--Kathy Keatley Garvey
Communications specialist
UC Davis Department of Entomology
(530) 754-6894
Mark your calenders!
The Honey and Pollination Center at the University of California, Davis, has postponed its "Luncheon in the Garden" initially set Sunday, June 2 from noon to 3 p.m. in the Good Life Garden at the Robert Mondavi Institute for Wine and Food Science on campus.
Executive director Amina Harris says plans call for the event to be rescheduled in October. it will be a "dazzling five-course meal from appetizers to cheese and desserts. Each course features honeys from around the globe."
The luncheon, open to the public, supports and introduces the Honey and Pollination Center. Food and drink will be provided by chefs, apiaries, wineries and meaderies (think wine made from honey), and the farmers of California.
What is the Honey and Pollination Center? Its vision is to establish UC Davis as a global center of excellence and education on bees, honey and pollination.
Its mission:
- Promote the use of high quality honey in the California market, help ensure the sustainability of honey production in California, and showcase the importance of honey and pollination to the well-being of Californians.
- Spearhead efforts to gain support and assemble teams for research, education and outreach programs for various stakeholder groups including: (1) the beekeeping industry, (2) agricultural interests who depend on bee pollination, (3) backyard beekeepers, and (4) the food industry
Its specific goals are five-fold:
- To optimize university resources by coordinating a multidisciplinary team of experts in honeyproduction, pollination and bee health
- To expand research and education efforts addressing the production, nutritional value, health benefits, economics, quality standards and appreciation of honey
- To serve the various agricultural stakeholders that depend on pollination services
- To help the industry develop informative and descriptive labeling guidelines for honey and bee-related products to establish transparency in the marketplace
- To elevate the perceived value of varietal honey to producers and consumers through education, marketing, and truth-in-labeling with the end goal of increasing the consumption of honey
For more information, contact events manager Tracy Diesslin at (530) 752-5233 or at tdiesslin@ucdavis.edu.
And if you'd like to make a donation, contact Harris at (530) 754-9301 or aharris@ucdavis.edu.
(Editor's Note: Here's the newly created Facebook page.)
April 3, 2013
No wonder. The insect, measuring about 1.5 millimeters long, is much smaller than a grain of rice.
Now, however, they can see a teddy-bear-sized version, thanks to a University of California, Davis entomology major Kristina Tatiossian, a member of the Research Scholars Program in Insect Biology.
Through the UC Davis Art/Science Fusion Program, Tatiossian, a junior, crafted a ceramic mosaic sculpture of the tiny walnut twig beetle for her research poster, “Flight Response of the Walnut Twig Beetle, Pityophthorus juglandis, to Aggregation Pheromones Produced by Low Densities of Males.”
The beetle jutting from the poster is so true to form that scientists studying the insect not only readily recognize it, but point out that it’s a female. That includes her mentor, chemical ecologist and forest entomologist Steve Seybold of the Davis-based Pacific Southwest Research Station, USDA Forest Service, and an affiliate of the UC Davis Department of Entomology.
Seybold and Andrew Graves, a former UC Davis researcher with the UC Davis Department of Plant Pathology, who now works for the USDA Forest Service, first detected the newly recognized beetle-fungus disease, known as Thousand Cankers Disease (TCD), in California in 2008. TCD had been detected earlier in Colorado and its impact had been noted even earlier in New Mexico, Oregon, and Utah. TCD and its history are chronicled in a newly revised “Pest Alert” issued by the USDA Forest Service.
The beetle, emerging from a gallery of a black walnut tree, is accurate right down to the concentric ridges that occur on the skin (cuticle) that protects its head. Some observers claim the beetle is smiling and could be a cartoon character.
Tatiossian completed the ceramic mosaic project over a four-week period. She earlier worked on two UC Davis Art/Science Fusion Program projects, including the “Tree of Life,” with the program’s founders, entomologist/artist Diane Ullman and artist Donna Billick. A former Los Angeles resident, Tatiossian will receive her bachelor’s degree in entomology this June and then plans to attend graduate school to study either biochemistry or virology.
Meanwhile, the poster is making the rounds. Tatiossian entered the poster in the Entomological Society of America’s student poster competition last year at its meeting in Knoxville, Tenn., where it drew lots of attention, not only for the research project but for the art.
Tatiossian will giving an oral presentation on her research at the Pacific Branch, ESA meeting, set for April 7-10 at South Lake Tahoe. Then she will display the poster again in the Undergraduate Research Conference at UC Davis on April 24 in Wellman Hall.
The disease is creating havoc throughout much of the western United States, Seybold said, and is now heading east. Its primary host is the black walnut tree but it also attacks other walnut trees.
On her poster, Tatiossian explained that the walnut twig beetle (WTB), in association with the fungus, causes the newly recognized disease, Thousand Cankers Disease. WTB vectors the fungal pathogen, which infects phloem tissue around the beetle galleries, she wrote. “Numerous localized infections have led to the common name of the disease.”
“Male WTB initiate new galleries and produce an aggregation pheromone, which can be used to study patterns of initial host colonization behavior of WTB. It has been previously shown by Graves and colleagues (2010) that as the number of males in a branch is increased from 20 to 200, the flight response of males and females is similarly increased,” she wrote. “We investigated flight responses to lower numbers of males in cut branch sections of northern California black walnut, Juglans hindsii.”
Her objective: “To determine the minimum number of males in an artificially infested branch of Juglans hindsii necessary to elicit a flight response from WTB.” She found that as little as one to five males is enough to elicit the aggregation response at her field study sites at two locations in Davis.
The poster will be displayed on the third floor of Briggs Hall, just outside the Department of Entomology’s administration office.
On her poster, Tatiossian credits Seybold; Extension entomologist Mary Louise Flint, associate director for Urban and Community IPM, UC Statewide Integrated Pest Program; entomology graduate student Stacy Hishinuma, and postdoctoral researcher Yigen Chen of the UC Davis Department of Entomology.
And the UC Davis Art/Science Fusion Program where the tiny walnut twig beetle sprang to life.
--Kathy Keatley Garvey
Communications specialist
UC Davis Department of Entomology
(530) 754-6894
