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Entomologist Helping Humankind
Bruce Hammock a distinguished entomology professor at the University of California, Davis, began his career trying to figure out how to control pests. Now he's making news with his potent enzyme inhibitor that dramatically reduces inflammation, inflammatory pain and neuropathic pain.
He couldn't have been more pleased or proud when a colleague in Spain published ground-breaking research on diabetes using the Hammock-discovered soluble epoxide hydrolase (sEH) inhibitor.
Researchers in the Joan Clària laboratory at the University of Barcelona, Spain, discovered that diabetes can be prevented and reversed, at least in genetically obese mice.
The study, published in the Proceedings of the National Academy of Sciences, revealed that when the sEH inhibitor was used in mice with a high level of omega-3 fats, the treatment both prevented the onset of diabetes and reversed the effects of diabetes in obese mice. Clària is an associate professor at the Barcelona University School of Medicine and a senior consultant at the Biochemistry and Molecular Genetics Service of the Hospital Clínic of Barcelona.
“Our previous studies show the drug we are working on will reduce the symptoms of diabetes in mice by itself,” Hammock said, “but the excitement about Joan Clària's work is that if the mice have a genetically increased level of omega-3 fatty acids--the drug offers prevention or cure in mice.”
This is breaking news that we hope will lead to targeting diabetes in humans. Worldwide, some 347 million people have diabetes, according to the World Health Organization. The Center for Disease Control and Prevention (CDC) estimates that 29.1 million Americans or 9.3 percent of the population have diabetes, either diagnosed or undiagnosed.
Hammock explained that the epoxide metabolites of the omega-3 fatty acid DHA are stabilized by inhibiting sEH, "and these metabolites contribute a great deal to the beneficial effects of an omega-3 diet." Previous UC Davis research in the laboratories of Bruce Hammock, Nipavan Chiamvimonvat, Robert Weiss, Anne Knowlton and Fawaz Haj showed that the enzyme reduces or reverses such diabetes-linked medical issues as renal failure, hypertension, diabetic pain, hardening of the arteries, and heart failure.
In the paper, titled “Inhibition of Soluble Epoxide Hydrolase Modulates Inflammation and Autophagy in Obese Adipose Tissue and Liver: Role for Omega-3 Epoxides,” Clària described the administration of the sEH inhibitor as “a promising strategy to prevent obesity-related co-morbidities.” Technically, the study “demonstrates that stabilization of cytochrome P-450 epoxides derived from omega-3 polyunsaturated fatty acids through inhibition of the inactivating enzyme soluble epoxide hydrolase (sEH) exerts beneficial actions in counteracting metabolic disorders associated with obesity, including insulin resistance and fatty liver disease,” Clària said.
Clària said the study also “sheds more light on the role of sEH in cellular homeostasis by providing evidence that omega-3 epoxides and sEH inhibition regulate autophagy and endoplasmic reticulum stress in insulin-sensitive tissues, especially the liver.”
Cristina López-Vicario was the first-author of the research paper. In addition to Clària and Hammock, other co-authors were José Alcaraz-Quiles, Verónica García-Alonso, Bibiana Rius, Aritz Lopategi, Ester Titos and Vicente Arroyo, all of the Clària lab or associates; and Sung Hee Hwang of the Hammock Lab, UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center
Hammock has worked on the mechanism of hydrolytic enzymes and their effect on human health for more than 35 years. He is developing both enzyme inhibitors and natural products as drugs for use in the United States and developing countries. His work has helped identify new targets for the action of drugs and other compounds to improve health and predict risk from various environmental chemicals.
Hammock is the founder and CEO of EicOsis, and through EicOsis, the compounds are in clinical trials for companion animals and the Pre-Investigational New Drug Application (Pre-IND) Consultation Program for neuropathic pain in human diabetics.
Hammock was recently selected a fellow of the National Academy of Inventors (NAI), which honors academic invention and encourages translations of inventions to benefit society and a member of the National Academy of Sciences. He directs the campuswide Superfund Research Program and National Institutes of Health Biotechnology Training Program.
Entomologist Bruce Hammock in his office in Briggs Hall. (Photo by Kathy Keatley Garvey)
Bruce Hammock: Scientist Extraordinaire
Research lab, yes. With colleagues, postdoctoral researchers, graduate students and undergraduate students, yes.
Hammock, a distinguished professor of entomology at UC Davis who holds a joint appointment with the UC Davis Comprehensive Cancer Center, has just been selected a fellow of the National Academy of Inventors (NAI), which honors academic invention and encourages translations of inventions to benefit society.
He is now one of five UC Davis NAI fellows, including Chancellor Linda P. B. Katehi, who was inducted in 2012; Jerry Woodall in 2013; and Kyriacos A. Athanasiou and M. Saif Islam), both elected this year with Hammock in the 170-member Class of 2014 fellows.
A member of the UC Davis faculty since 1980, Hammock has made major innovations in multiple fields. Most recently his laboratory found potent enzyme inhibitors that dramatically reduce inflammation, inflammatory pain and neuropathic pain. He is the founder and CEO of EicOsis, and through EicOsis, the compounds are in clinical trials for companion animals and the Pre-Investigational tional New Drug Application (Pre-IND) Consultation Program for neuropathic pain in human diabetics. Hammock is developing both enzyme inhibitors and natural products as drugs for use in the United States and developing countries. In agriculture, his laboratory developed the first recombinant viruses as greeninsecticides, while in environmental chemistry, they pioneered the use of immunodiagnostics for environmental analysis and biosensor development, currently applying alpaca nanobodies to sensor technology.
Hammock is a member of the U.S. National Academy of Sciences, a fellow of the Entomological Society of America, and the recipient of the Bernard B. Brodie Award in Drug Metabolism, sponsored by the America Society for Pharmacology and Experimental Therapeutics. He directs the campuswide Superfund Research Program, National Institutes of Health Biotechnology Training Program, and the National Institute of Environmental Health Sciences (NIEHS) Combined Anayltical Laboratory.
Hammock, who received his bachelor of science degree magna cum laude from Louisiana State University in entomology and chemistry, and his doctorate from UC Berkeley in entomology and toxicology, working in xenobiotic metabolism, describes himself as a basic scientist who “sometimes fines something interesting.” He attributes his success to “having wonderful colleagues and students.”
He also describes himself as “an avid, if incompetent hiker and climber,” and occasionally teaches white-water kayaking with UC Davis Outdoor Adventures. By the way, he and his lab also holds an annual water balloon battle outside Briggs Hall every summer. It's usually amounts to a 10-minute battle because the Hammock lab works hard and plays hard.
NAI, founded in 2010, now has 414 fellows representing more than 150 prestigious research universities and governmental and non-profit research institutions. Included: 61 presidents and senior leadership of research universities and non-profit research institutes, 208 members of the other National Academies, 21 inductees of the National Inventors Hall of Fame, 16 recipients of the U.S. National Medal of Technology and Innovation, 10 recipients of the U.S. National Medal of Science, 21 Nobel Laureates, 11 Lemelson-MIT prize recipients, 107 Fellows of the American Association for the Advancement of Science, and 62 fellows of the Institute of Electrical and Electronics Engineers.
Congratulations, Professor Hammock! Getting elected “is a high honor bestowed upon academic innovators and inventors who have demonstrated a prolific spirit of innovation in creating or facilitating outstanding inventions and innovations that have made a tangible impact on quality of life, economic development, and the welfare of society,” NAI officials said.
Bruce Hammock is a new fellow of the National Academy of Inventors. (Photo by Kathy Keatley Garvey)
Bruce Hammock in a hammock--something you don't see often! (Photo by Cindy McReynolds)
'The Well': The Hammocks Did It Well
Just because an entomologist is cast in a Hollywood movie, that doesn't mean there will be bugs.
Bruce Hammock, distinguished professor of entomology at the University of California, Davis, and his wife, Lassie, recently headed to the Los Angeles Film Festival for the premier showing of “The Well,” directed by their son, Tom Hammock.
The parents play minor roles in the film, a thriller set in a futuristic dust bowl.
“It was too cold for bugs,” said Professor Hammock of the December 2013 filming in a secluded area of the high desert, near the Mojave.
“No bugs were featured in the film,” Tom confirmed. “But there were bugs around the set. A few velvet ants, for sure.”
The film marks Tom Hammock's debut as a director and Bruce and Lassie Hammock's debut as actors.
At the edge of a barren valley, all that remains of the Wallace Farm for Wayward Youth is a few hollowed-out husks of buildings and the memories of Kendal, a seventeen-year-old girl who can barely recall when the valley was lush. It's been a decade since the last rainfall, and society at large has dried up and blown away. Only Kendal and a few others remain, barely scraping by while dreaming of escape. When a gang leader named Carson lays claim to what little precious water remains underground, Kendal must decide whether to run and hide or bravely fight for what little she has left in this post-apocalyptic thriller.
The film stars Haley Lu Richardson, Booboo Stewart, Max Charles, Nicole Fox, Michael Welch and Jon Gries. Critics are praising the Tom Hammock-directed film as "superb" and looking forward to more of his work.
Wrote “Hammock's direction is superb; every moment of every scene matters, and the film shifts between action and drama superbly. Cinematographer Seamus Tierney also deserves kudos; considering how many scenes in the film incorporate both dark hiding places and the sun-razed landscape around them, the shots are always clean, clear and, in their way, beautiful. The Well"has its pleasures and powers, as well as a distinctive take on what could have been familiar, dead material; Hammock may have begun his career making worlds for other directors, but given a chance to create his own here, he not only succeeds but excels.”
Although new to acting business, Bruce Hammock is not new to "directing." In addition to his joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center, he directs the campuswide Superfund Research Program, National Institutes of Health Biotechnology Training Program, and the National Institute of Environmental Health Sciences (NIEHS) Combined Analytical Laboratory. Bruce also is an athlete who loves rock climbing and white-water rafting and water balloon battles. (He will host the annual Bruce Hammock Water Balloon Battle--10 minutes of aim--on Thursday, July 24 on the Briggs Hall lawn for his students, researchers and colleagues.)
In "The Well," however, Bruce Hammock does not look like a professor, a researcher, an athlete or a water warrior. For the shoot, he grew a beard, donned his father's old ragged World War II clothes and worn-out shoes, and practiced looking (1) forlorn and haggard and (2) like a corpse.
“It was very interesting,” the professor told us last December. “But my, the producers work hard. We were on the set at 5:30 a.m. We worked until dark, in weather well below freezing, with high winds blowing sand. The professional actors and actresses put in amazing performances under quite adverse conditions."
“They're a very professional and fun group. I had never realized the complexity of filming a movie. I hope they pull off their vision.”
Tom Hammock is obviously multitalented. He served as the production designer for the critically acclaimed horror films, "All the Boys Love Mandy Lane" and "You're Next," and also worked on such film productions as “Breaking Bad,” “Dexter,” “Charlie and the Chocolate Factory." A 1994 graduate of Davis High School, he received his bachelor's degree in landscape architecture from UC Berkeley, and then studied film design at the American Film Institute. He is now very much involved in the hugely popular young adult and horror film genre, but showed more of his talent when he authored the original graphic novel, “An Aurora Grimeon Story—Will O' the Wisp." (See previous Bug Squad blog)
Release date of "The Well?"
Well...the next step is to find a buyer. Directors are fully aware that sometimes this can take months or years.
Meanwhile, Bruce Hammock doesn't intend to quit his day job, but he could--if he wanted to--add "acting" to his resume.
Professor Bruce Hammock in his office in Briggs Hall, UC Davis campus. (Photo by Kathy Keatley Garvey)
It All Began With Bugs
That's where it usually begins when your father is an entomologist.
Tom Hammock, son of distinguished professor Bruce Hammock, of the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center, learned about insects early in life. Young Tom caught, sketched and released such insects as dragonfiles, damselflies and wasps.
"He didn't want to kill them," his father recalled.
Tom took art lessons from noted scientific illustrator Mary Foley Benson, and initially pondered a career as a scientific illustrator. He considered biology as a college major, and finally, landscape architecture. After graduating from UC Berkeley with a degree in landscape architecture, Tom studied film design at the American Film Institute and worked on such films as Breaking Bad, Dexter and Charlie and the Chocolate Factory.
Tom, who now lives in Hollywood, is better known for his work in the wildly popular young adult and horror genre, including "You're Next!" and "All the Boys Love Mandy Lane."
"Will o' the Wisp" is based on many of his father's childhood memories of the Deep South. Bruce Hammock, born in Little Rock, Ark., and a graduate of Louisiana State University, beguiled him with fascinating stories about southern swamps and will o' the wisps, his pet raccoon, a biological supply company, venomous creatures, and dermestid beetles, used to clean animal skeletons.
You'll read about them--and more--in "Will o' the Wisp."
“Almost no one writes for girls and almost no one writes for girls dealing with girls and science,” Tom said. “Graphic novels for girls are rare and have a tough road in the publishing world.”
Assorted bugs, including butterflies, scorpions, fireflies, mosquitoes, beetles and spiders, find their way into the book. And a tattoo of a dermestid beetle found its way on Hutchison's arm. (For more information on the graphic novel, access ossuaryisle.com, and then check out the trailer, Facebook page, and YouTube video.)
"Will o' the Wisp" is drawing rave reviews, and rightfully so. Already it has been nominated for "best young adult graphic novel" award from the American Library Association.
The Hammock-Hutchison team plans to make this a trilogy.
One online comment, with triple exclamation points, says it all: "OMG!! This was so good. I hope and hope and hope there will be more!!!!"
Looking back, entomologist Bruck Hammock commented: "Tom was always interested in landscape, art, and biology. However, film and graphic novels are so far from my background, I never saw this as a career path. In retrospect it is obvious."
And it all began with bugs.
Tom Hammock, a renaissance man, has authored a graphic novel featuring a girl scientist who solves mysteries in a southern swamp. (Photo by Kathy Keatley Garvey)
Exciting News from the Hammock Lab
In research led by postdoctoral researcher Zuodong Zhang, a team of 16 scientists discovered a key mechanism by which dietary omega-3 fatty acids (fish oils) could reduce the tumor growth and spread of cancer, a disease that kills some 580,000 Americans a year.
The research is published today (April 3) in the Proceedings of the National Academy of Sciences (PNAS). They 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.
“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 who focuses his research on lipid mediators on angiogenesis, tumor growth and metastasis. “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.”
The studies, conducted on mice, also suggest that a combination of omega-3 diet and some anti-cancer drugs such as sorafenib, “could not only be efficacious to treat cancers but reduce potential side effects,” said Zhang, who received his doctorate in food science from the University of Wisconsin-Madison.
“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.”
“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.”
Said cardiologist Jonathan Lindner of the Oregon Health & Science University: “New drug strategies for fighting cancer could emerge from knowledge of how the body uses nutrition to promote health. Diet has been shown to influence susceptibility to many types of cancer, and also to influence rate of tumor progression and response to chemotherapy. This information has been leveraged to make reasonable recommendations on diet in patients with cancer. Perhaps more importantly, by uncovering how diet influences tumor development and growth, it may be possible to develop new drugs that work through the same beneficial pathways.”
“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.”
Read more about the research on the UC Davis Department of Entomology website and see photos of some of the co-authors.
UC Davis postdoctoral researcher Zuodong Zhang. (Photo by Kathy Keatley Garvey)
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