UC Davis distinguished professor Bruce Hammock, who holds a joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Society, is known for his expertise in chemistry, toxicology, biochemistry and entomology. He meshes all four sciences in his 50-year research on how environmental chemicals impact human health.

And now, the company he founded, EicOsis LLC, to develop a non-opiate drug to relieve inflammatory pain in companion animals and target chronic neuropathic pain in humans and horses, can add “Sacramento Region Innovator of the Year” to its list of accomplishments.

EicOsis won the award in the medical health/biopharmaceutical category of the annual Sacramento Region Innovation Awards Program.  The program “recognizes the area's vibrant innovation community—from emerging to established companies—and their breakthrough creations,” according to sponsors Stoel Rives LLP, Moss Adams LLP and the Sacramento Business Journal.

“This project is an illustration of how fundamental science leads to real world applications, in this case addressing severe pain of humans and companion animals,” said Hammock, chief executive officer of EicOsis and a UC Davis faculty member who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. “Our success in translation has been due largely to support from a number of institutes of the National Institutes of Health and a small team of hard-working scientists.” 

The ceremony, honoring the winners of the eight categories, took place Nov. 7 in the Crest Theatre, Sacramento. Judges scored the finalists on novelty, market need, economic or social impact and disruption. (See more information on YouTube (the EicOsis award presentation starts at 1:05.)

“It was an honor to be awarded the Sacramento Region Innovator of the Year in Medical Health and BioPharma,” said Cindy McReynolds, senior program manager of EicOsis and a UC Davis doctoral candidate studying pharmacology and toxicology.  “The companies represented were inspiring, and it is great to be a part of the innovation going on in the Sacramento region.”

“Chronic pain is an enormous emotional and economic burden for more than 100 million people in the United States alone,” said Hammock, who co-founded EicOsis in December 2011 to alleviate pain in humans and companion animals. “The extreme and poorly treated pain that I observed as a medical officer working in a burn clinic in the Army, is a major driver for me to translate my research to help patients with severe pain.”

EicOsis, based in Davis, is developing a new class of oral non-narcotic analgesics based on inhibition of the soluble epoxide hydrolase (sEH) enzyme. The sEH inhibitors have already shown to be effective for inflammatory and neuropathic pain in the rodents, horses, dogs and cats, with no apparent adverse or addictive reactions.

Phase 1 human clinical trials to test the drug candidate, EC5026, a first-in-class, small molecule that potently inhibitssEH, will begin Dec. 10 in Texas. The title: "A Single-Center, Double-Blind, Placebo-Controlled, Phase 1a Single Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Sequential Dose Regiments of Oral EC5026 in Healthy Male and Female Subjects." Eight will participate; six with the drug candidate and two  with the placebo. The technology was discovered in the Hammock lab and UC Davis has licensed patents exclusively to EicOsis.

“EC5026 is a key regulatory enzyme involved in the metabolism of membrane fatty acids,” Hammock said. "It's a novel, non-opioid and oral therapy for neuropathic and inflammatory pain. Inhibition of sEH treats pain by stabilizing natural analgesic and anti-inflammatory mediators."

The project is unique in that “there have been very few truly new types of analgesic compounds that have reached the market in the past 50 years,” Hammock said.

“The sEH enzyme is involved in regulating the activity of powerful anti-inflammatory fatty acids called EETs that are present in all cells in humans and animals,” the scientists explained in their awards application. “EETs are anti-inflammatory, analgesic, anti-hypertensive, but they are short lived molecules that are normally eliminated within seconds. By inhibiting sEH, EET levels can be increased by 4x or more and maintained at high anti-inflammatory and analgesic levels for 24 hours or longer.”

“The sEH inhibitors are very potent molecules that are designed for once daily oral dosing. They can also be administered intravenously for acute pain (e.g. equine laminitis),” they wrote. “Preclinical safety studies show that sEH inhibitors are very safe with no visible signs of toxicity at doses more than 100x higher than the therapeutic dose levels. Unlike conventional analgesics, they do not produce sedation or cognitive dysfunction and they have been shown to have no addiction liability, no adverse cardiovascular effects, and no adverse effects on the gastrointestinal tract. They can be safely co-administered with existing analgesic medications.”

Approximately 50 million Americans (20 percent of the population) suffer from chronic pain, according to the Center for Disease Control and Prevention. The annual economic toll is $560 billion, encompassing direct medical expenses, lost productivity, and disability claims. Pain research is now one of the top priorities of the National Institutes of Health (NIH).

EicOsis advancement of EC5026 into clinical trials has been funded as part of the Blueprint Neurotherapeutics Network (BPN) of the NIH Blueprint for Neuroscience Research. The BPN is a collaboration of NIH Institutes and Centers that supports innovative research on the nervous system with the goal of developing new neurotherapeutic drugs.

EicOsis (pronounced eye-cosis), derives its name from eicosanoid, “the major backbone of chemical mediators in the arachidonate cascade,” said McReynolds. “It symbolizes the epoxide group in chemistry, which is key to the anti-inflammatory chemical mediators and where the biochemical target called soluble epoxide hydrolase works.”

Let's see...John Casida, Bruce Hammock and now Thomas Sparks. You probably recognize their names as exemplary scientists affiliated with the University of California system. They all meshed entomology, chemistry and toxicology and biochemistry.

But did you know that they are all interlinked and that each won the prestigious Kenneth A. Spencer Award of the American Chemical Society (ACS)? They represent three generations of scientists--knowledge passed from Casida to Hammock to Sparks.

Thomas Sparks, the first graduate student of UC Davis distinguished professor Bruce Hammock, is the 2019 recipient, following in the generational footsteps of Hammock, his major professor at UC Riverside and UC Davis; and Hammock's major professor, the late John Casida of UC Berkeley.

Sparks accepted the award at the recent ACS meeting in San Diego. Hammock received the Spencer award in 1993, and Casida in 1978.

In his talk, Sparks acknowledged that he was a “third generation winner” following Casida and Hammock. "I was surprised to get a very large response/applause for this--very gratifying and likely testimony to the high regard for John Casida and Bruce Hammock."

"I was there cheering for Tom," Hammock said. "He gave a wonderful talk.  Actually, I was there with Tom and our wives and my second student Keith Wing."

Casida, Hammock, Sparks and Wing also won the ACS International Award for their research: Casida, the inaugural winner, won it in 1969; Hammock in 1992; Sparks in 2012, and Wing in 2015.

Said Sparks: "As an aside, Vince Salgado, who worked in the lab next to Keith and I in Riverside got the International Award this year (2019)--perhaps something in the water or atmosphere."

Sparks, a native of San Francisco who grew up in a farming community in the central valley, is an internationally recognized leader in the discovery of new insect control agents, the biochemistry and toxicology of insecticides, and insecticide resistance. Formerly a professor at Louisiana State University (LSU) and then a researcher in private industry for three decades, he recently retired as a research fellow from Corteva Agriscience (formerly Dow AgroSciences).

“Tom was instrumental in the discovery and development of a new class of insecticides called spinosids,” said Hammock, who holds a joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. Spinosad, launched in 1997, is a naturally occurring mixture of spinosyns. Sparks co-invented the next-generation semi-synthetic spinosyn-based insecticide, spinetoram, that improved the efficacy, spectrum, and residual of spinosad. Both compounds received the EPA Presidential Green Chemistry Challenge Award, spinosad;in 1999 and spinetoram in 2008.

Always keenly interested in insects and later, chemistry, Sparks obtained his bachelor's degree in biology, with a minor in chemistry, in 1973 from California State University, Fresno. He then headed to UC Riverside for his doctorate to study insect endocrinology, biochemistry, and toxicology with Hammock. Sparks received his doctorate in 1978 from UC Riverside. When Hammock joined the UC Davis faculty in 1980, Sparks continued his work with him, and while on the faculty of LSU, completed a sabbatical at UC Davis.

Sparks praised the broad training and inspiration he received in Hammock's lab as “outstanding preparation for my future roles in science.” 

Sparks served on LSU's Department of Entomology faculty from 1978 to 1989 as an insect toxicologist, achieving full professor. His research covered endocrine regulation of insect metamorphosis, insecticide resistance, and insecticide biochemistry and toxicology.

In 1989, Sparks joined the agrochemical research group, the joint venture between Eli Lilly and The Dow Chemical Company, DowElanco (later known as Dow AgroSciences). He worked in discovery research for nearly three decades.

Sparks holds 46 patents or patent applications and continues to publish widely. He has published more than 175 refereed journal publications, book chapters, and other articles. Many involve a variety of discovery efforts in innovative insecticidal chemistries.

In recognition of this work, Thomas was named R&D Magazine's 2009 Scientist of the Year, the first in the 50-year history of the award for a scientist working in the field of agriculture. He also received the ACS International Award for Research in Agrochemicals (2012) and the AGRO Award for Innovation in Chemistry of Agriculture (2015). He is a Fellow of the Entomological Society of America and, in 2018, received the Entomological Society of America Recognition Award in Insect Physiology, Biochemistry and Toxicology.  

Other UC Davis-affiliated recipients of the Spencer Award include the late Emil Mrak, for whom Mrak Hall is named.

The award memorializes Kenneth A. Spencer (1902-1960), a Kansas City geologist, engineer, coal miner, philanthropist and owner of the Spencer Chemical Company. 

Our story begins with a kid bred and born in Arkansas.

You may have seen the news article about the distinguished professor at the University of California, Davis, who won a $6 million, eight-year "Outstanding Investigator" federal grant for his innovative and visionary health research. The award, part of the Revolutionizing Innovative, Visionary Environmental Health Research (RIVER) Program of the National Institutes of Environmental Health (NIEHS), is given rarely and is based on a track record of innovation and a "visionary" proposal to address serious problems in environmental health.

The kid born in Little Rock, Ark. who went on to win the prestigious grant is Bruce Dupree Hammock, who holds a joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Society. He is known for his expertise in chemistry, toxicology, biochemistry and entomology. He meshes all four sciences in his 50-year research on how environmental chemicals impact human health.

Born to a father who worked for the U.S. Post Office, and a mother who sold World Book Encyclopedias, Bruce slipped into science as naturally as he slipped into learning more about the world around him.

"I collected insects, kept snakes, lizards, frogs, raccoons, possums, and a deer, etc.," he said, "and I loved the outdoors,  canoeing, climbing and hiking.  I went into forestry but became interested in a forest insect outbreak, then insects, then pesticides etc.  It is hard to say where science leads. I was lucky in having an inspirational scoutmaster E.A. Bowen, who was a wonderful naturalist, a wonderful guy.  He was also my dad's scoutmaster, an American Indian. My parents had to leave me on my own for several months when I was 16, and a wonderful biology teacher arranged for me to have a microscope and lab in a room at the high school and suggested ecology projects for me to do in local woods."

The rest, they say, is history. Remarkable history.

Hammock, now a septuagenarian,  received his bachelor's degree in entomology (with minors in zoology and chemistry) magna cum laude from Louisiana State University, Baton Rouge, in 1969. He received his doctorate in entomology-toxicology from UC Berkeley in 1973 with John Casida at UC Berkeley. Hammock served as a public health medical officer with the U.S. Army Academy of Health Science, San Antonio, and as a postdoctoral fellow at the Rockefeller Foundation, Department of Biology, Northwestern University, Evanston, Ill. He joined the UC Davis Department of Entomology (now the Department of Entomology and Nematology) in 1980.

“I am thrilled to receive the RIVER award,” said Hammock, who devotes much of his research toward environmental health. “The National Institutes of Health has many institutes and several of them have funded my laboratory over the years.  But it is the NIEHS that most closely matches my interests.  They have supported my work since I was a graduate student, so I am particularly thrilled they have shown such high confidence in the science and work our laboratory does.  This award certainly recognizes the current and past members of the laboratory who have been so productive and innovative.”

The program provides $6 million in funding over an eight-year period “to give scientists greater intellectual and administrative freedom as well as sustained support to achieve greater scientific impact,” according to NIEHS officials. RIVER provides a select few scientists with great latitude in addressing the most pressing scientific problems.

“Professor Hammock is especially deserving of this recognition for his important research over many years,” said Helene Dillard, dean of the UC Davis College of Agricultural and Environmental Sciences. “Environmental health is central to the mission of our college, and we anticipate that this award will empower him to continue making advances in areas with the potential to impact human well-being.”

Ken Burtis, faculty advisor to the Chancellor and Provost and past Dean of Biological Sciences at UC Davis, said it would be difficult to find “a more deserving scientist to invest in than Bruce Hammock.”

“We both worked in the same building, and Bruce was one of the most hard-working, creative and enthusiastic colleagues I knew,” Burtis said. “The grant process often limits innovation. The intellectual freedom NIEHS is providing Hammock makes our university shine and is a smart investment on the part of the agency. Their investment in him in the past paid off and RIVER will pay off even more in the future.” When asked how the award would change his life, Hammock, a kayak enthusiast and instructor, responded: “I will give up kayaking the harder rivers, I certainly do not want to drown and have to give any of the funding back. Having been given this great freedom, it will be hard to live up to the expectations.”

Hammock, who has directed the NIEHS-UC Davis Superfund Research Program for the past 35 years, said many of his UC Davis collaborators are affiliated with the Superfund Program, including:

• Professor Aldrin Gomes who holds a joint appointment with the Department of Neurobiology, Physiology and Behavior, College of Biological Sciences, and the Department of Physiology and Membrane Biology, School of Medicine;
• Fawaz Haj, who holds a joint appointment with the Department of Nutrition, College of Agricultural and Environmental Sciences, and the Department of Internal Medicine, School of Medicine
• Research scientist Christophe Morisseau of the Hammock lab, Department of Entomology and Nematology and the Comprehensive Cancer Center, and
• Cardiologist Nipavan Chiamvimonvat of the Division of Cardiovascular Medicine, Department of Internal Medicine, UC Davis Health System

“Bruce had been wonderful supporting students through running a training grant and particularly bringing diverse scientists together with the NIEHS Superfund Program,” said Chiamvimonvat. “It has been such a privilege to be part of this exciting program to understand the mechanisms of environmental contaminants on human health. His pioneering work on novel targets to combat inflammation has far-reaching applications, not only in pain, but also in other diseases including cancer and cardiovascular diseases, the two most common causes of morbidity and mortality.”

Gomes explained that rather than trying to find biological markers for individual environmental chemicals, this Superfund group is working together to find universal markers of stress and disease and understand how to prevent these diseases.  ‘By stabilizing mitochondria, the endoplasmic reticulium and other cell organelles to stress,” Gomes said, “we are reducing toxicity, as well as understanding the very basis of tissue damage by commonly used drugs and pesticides and how to reverse it.”

Michael Lairmore, dean of the UC Davis School of Veterinary Medicine, said he was pleased to hear that Hammock has won the NIEHS River Award. “Bruce is very deserving of this award,” Lairmore said. “He has pioneered trans-disciplinary research across campus and has engaged faculty in multiple colleges and schools to transform the way we treat diseases in multiple species.  His creative approaches blend his natural curiosity with practical ways to translate his research findings into real world solutions to disease processes.”

“By providing research freedom through the RIVER award to Bruce Hammock, NIH made a remarkable decision,” said Scott Fishman, director of the Center for Advancing Pain Relief, Fullerton Endowed Chair in Pain Medicine, and executive vice chair of the Department of Anesthesiology and Pain Medicine for the UC Davis School of Medicine.

“For example, Bruce sought me out shortly after I arrived at UC Davis with interest in reducing pain and our excessive use of opioids,” Fishman said. “Over time, he went on to develop an experimental pharmaceutical that is a promising unique non-opioid drug for treating chronic pain that will enter human trials this fall.  With Hammock as a recipient, the NIH RIVER Program has declared its commitment to recognizing basic scientists who are developing profound solutions that address the opioid crisis.”

Harvard Medical School researcher and former physician, Dipak Panigraphy, said that “The pioneering studies from the Hammock laboratory not only have elucidated how certain environmental contaminants increase cancer risk, but our collaborative work shows promise for preventing metastasis and recurrence of cancer following surgical tumor resection and chemotherapy. These potentially paradigm shifting studies show that preoperative or peri-chemotherapeutic management of inflammation may stave off cancer recurrences.”

Said Hammock: “We would not have this without the scientific and intellectual input of Cindy McReynolds, program manager of the Superfund Program. Of course RIVER is a complement to the existing and past scientists who have worked on this project.”

The RIVER program is “the centerpiece of an emerging effort to support people, not projects, by providing support for much of an independent research program for outstanding investigators and giving them intellectual and administrative freedom, as well as sustained support, to pursue their research in novel directions in order to achieve greater impacts,” according to the NIEHS-RIVER website. “The RIVER program rewards outstanding environmental health sciences researchers who demonstrate a broad vision and potential for continuing their impactful research with increased scientific flexibility, stability in funding, and administrative efficiency.”

Nationally recognized for his achievements, Hammock is a fellow of the National Academy of Inventors, which honors academic invention and encourages translations of inventions to benefit society. He is a member of the U.S. National Academy of Sciences, a fellow of the Entomological Society of America, and the recipient of scores of awards, including the first McGiff Memorial Awardee in Lipid Biochemistry; and the Bernard B. Brodie Award in Drug Metabolism, sponsored by the America Society for Pharmacology and Experimental Therapeutics.

“Bruce Hammock and his research team are the perfect example of how UC Davis translates university research into societal impact,” said Dushyant Pathak, associate vice chancellor for Innovation and Technology Commercialization in the UC Davis Office of Research.

“As a result of their fundamental work in unraveling both insect and human regulatory biology, the Hammock laboratory elucidated a biochemical pathway that regulates inflammation, pain and senescence,” Pathak said. “Enabled by this knowledge, a novel drug candidate to treat chronic pain is expected to enter human phase 1a trials this fall--also supported by NIH. The drug is licensed by the university to EicOsis, a company that is directing its development and is a UC Davis spin-off.”

Hammock traces the history of his enzyme research to his studies in the Casida laboratory.  He was researching insect developmental biology and green insecticides when he and colleague Sarjeet Gill, now a distinguished professor at UC Riverside, discovered the target enzyme in mammals that regulates epoxy fatty acids.

“My research led to the discovery that many regulatory molecules are controlled as much by degradation and biosynthesis,” Hammock said. “The epoxy fatty acids control blood pressure, fibrosis, immunity, tissue growth, depression, pain and inflammation to name a few processes.”

“Basically, I began by trying to figure out how a key enzyme, epoxide hydrolase, degrades a caterpillar's juvenile hormone, leading to metamorphosis from the larval stage to the adult insect,” Hammock said. He asked himself these questions: “Does the enzyme occur in plants? Does it occur in mammals?" It does, and particularly as the soluble epoxide hydrolase in mammals.

"It is always important to realize that the most significant translational science we do in the university is fundamental science,” said Hammock, marveling that “this work to treat pain in companion animals, horses and humans all began by asking how caterpillars turn into butterflies.”

Related links:

• Bruce Hammock Laboratory Receives $6 Million/8-Year NIEHS RIVER Award
• UC Davis and EicOsis in Bloomberg - Business Week on Opioid Replacements for Pain Treatment
• 16th Annual Water Balloon Battle (The Hammock lab works hard and plays hard)

He wasn't invited, but he crashed the party anyway.

A few minutes before the 16th annual Bruce Hammock Lab Water Balloon Battle began on the Briggs Hall lawn at the  University of California, Davis, water warrior Jasmine Morriseau, 10, noticed "something" on the head of her twin brother, Cedric.

Could it be? It was. An immature praying mantis.

Specifically, a male Stagmomantis limbata, as identified by praying mantis expert Lohitashwa “Lohit” Garikipati. “I'd guess 5th instar by the size of the wingpads,” said Garikipati, a Bohart Museum of Entomology associate who just recently received his bachelor's degree in entomology.

It's not every day—or every year—that a praying mantis joins an entomologically based water balloon battle

The twins showed the insect, also known as a bordered mantis, to their older sister Evelyne, 15, and to their father Christophe Morisseau, a research scientist in the Hammock lab who coordinates the annual water balloon battles.

And then Jasmine gingerly placed the praying mantis on a nearby bush, out of the line of fire and out of the 96-degree heat.

Then, and only then, did the battle begin.

The annual battle, aka “Bruce's Big Balloon Battle at Briggs,” is the brainchild of Bruce Hammock, a distinguished professor who holds a joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. It's a way of showing  camaraderie and engaging in a little fun. They fill and toss 2000 water balloons, and then empty tubs of water on unsuspecting lab mates.

It's an international soakfest: the Hammock lab includes 30 researchers from eight countries: United States, China, France, Ukraine, Lebanon, Japan and Korea. United Stares, China, France, Ukraine, Lebanon, Japan, Korea and Viet Nam.

Sometimes other labs join in the fun, as did the scientists this year and last year in the Aldrin Gomes lab, UC Davis Department of Neurobiology, Physiology and Behavior.

The water warriors are so skilled that the battle usually lasts about 15 minutes—15 minutes of aim. Then they remove all the balloon remnants from the lawn, pose for their annual group photo, and head back to work.

Morisseau says that water balloon battles “provide team building efforts, stress relief and healthy exercise.” He created and displayed a poster, “Health Benefits of Water Balloon Fights,” last year at the Hammock Lab Alumni Reunion. “We recommend that any workplace establish water balloon fights on a yearly or twice yearly basis,” Morisseau concluded.

“We work hard and play hard,” said Hammock, a member of the UC Davis faculty since 1980 and the director of the National Institute of Environmental Health Sciences (NIEHS)-UC Davis Superfund Research Program. Trained in chemistry, toxicology, biochemistry and entomology, he now targets chronic pain in humans and companion animals. For the past 20 years, the Hammock lab has been researching an inhibitor to an enzyme, epoxide hydrolase, which regulates epoxy fatty acids.  “My research led to the discovery that many regulatory molecules are controlled as much by degradation and biosynthesis," Hammock said. "The epoxy fatty acids control blood pressure, fibrosis, immunity, tissue growth, depression, pain and inflammation to name a few processes.”

Hammock co-founded EicOsis LLC, a Davis-based company that recently received a $5 million investment from Open Philanthropy to move original research developed in the Hammock lab into human clinical trials. (See news story.) Nationally recognized for his scientific achievements, he is a fellow of the National Academy of Inventors, which honors academic invention and encourages translations of inventions to benefit society.

The Hammock lab also knows how to translate science into watery fun on a hot summer day.