PNAS paper

Every year some 10,000 burn victims in the United States undergo an acute inflammatory reaction and die of burn-related infections, according to the Centers for Disease Control and Prevention. 

Now a newly published study by a research team from the laboratory of distinguished professor Bruce Hammock,  University of California, Davis, and the Department of Surgery, University of Cincinnati College of Medicine (UC CoM), has identified a key regulatory mechanism in inflammation that may lead to new targets for resolving that inflammation—and the inflammation of patients with sepsis, cancer and COVID.

In research published in the current edition of Proceedings of the Natural Academy of Sciences, the scientists announced that they have discovered a pathway that regulates the immune response after infection or injury, such as burns. Dysregulation of this pathway could differentiate those who are at risk of fatal sepsis or help identify targets to resolve this unregulated inflammation.

“We are very excited about the findings in this paper and the far-reaching impacts it could have on understanding a key regulatory step in the immune response,” said co-lead author and researcher Cindy McReynolds of the Hammock lab and director of research at EicOsis, a Davis-based company founded by Hammock. Hammock, the corresponding author of the publication, has been involved in enzyme research for more than 50 years. 

The eight-member team, using a rodent model, found that the metabolites of linoleic acid formed by the enzyme, soluble epoxide hydrolase (sEH), drive deleterious inflammation after injury. These metabolites, known as lipid mediators, regulate inflammation, blood pressure and pain. Drugs that inhibit the sEH enzyme and resolve inflammation could lead to a better patient outcome. 

“Our previous work identified that these same lipid mediators were up-regulated in severe COVID infections, and we are now finding that these compounds play a role in modulating the immune response so that the body is unable to fight infection or respond properly to trauma without leading to a potentially fatal overreaction,” said McReynolds, who holds a doctorate in pharmacology and toxicology from UC Davis. 

“This dysregulation has fatal consequences in serious diseases such as COVID, cancer, sepsis, burn, where fatality rates can be as high as 40 percent in severe cases,” she said. “An understanding of these pathways can help identify patients at risk of developing serious disease or identify new therapeutic targets for treatment.” 

“The immunological disbalance we see in many cases of severe burn injury, trauma and sepsis pose a huge clinical challenge as we lack the understanding of how to diagnose and treat it,” said co-lead author Dr. Christian Bergmann, formerly with UC CoM's Department of Surgery and now headquartered in Germany with the University of Ulm's Department of Trauma Surgery, Hand, Plastic and Reconstructive Surgery. “With this work, we reveal an important mechanism how immune cells are functionally disabled by sEH-derived metabolites of linoleic acid.” 

“The natural compounds we are studying in this paper are metabolites of linoleic acid (LA), an essential fatty acid the body needs in very small amounts to survive and is only available through the diet,” McReynolds explained. “At lower concentrations, these metabolites are necessary for regulating thermogenesis and heart health but promote inflammation at higher concentrations. LA is more stable and much cheaper than longer chain polyunsaturated fatty acids, so heavily processed foods have higher LA content to increase shelf-life. Additionally, agricultural practices, such as feeding animals corn-based diets, have increased LA in meats and dairy products.” 

Charles Caldwell, professor and director, Division of Research, UC CoM Department of Surgery

“As a result, we are consuming the highest amount of linoleic acid and have the highest recorded concentration of LA in our fatty tissue in human history," McReynolds said. "As our bodies respond to stress or disease, we metabolize LA into the regulatory metabolites that were monitored in this paper. At higher concentrations, the immune system was unable to properly respond to infection, thereby promoting a sustained immune response. These observations are important in inflammatory- driven diseases, such as sepsis and COVID, but could also be important in understanding many of the increased chronic diseases we are seeing in our population.” 

The research, titled "sEH-Derived Metabolites of Linoleic Acid Drive Pathologic Inflammation while Impairing Key Innate Immune Cell Function in Burn Injury,” is co-authored by Debin Wan, formerly of the Hammock lab and now a scientist at Escape Bio, San Francisco; Nalin Singh of the Hammock lab; and three UC CoM researchers: Charles Caldwell, professor and director, Division of Research, Department of Surgery; Dorothy Supp, adjunct professor in the Department of Surgery and a scientific staff member at Shriners Children's Ohio; and Holly Goetzman, principal research assistant in the Caldwell lab.

“Chronic pain is an enormous emotional and economic burden for more than 100 million people in the United States alone,” said co-author Hammock, who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. "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 laboratory research to help patients with severe pain and at risk from sepsis." Another major influence: his mother served 15 years as a nurse in a children's hospital burn center, caring for hundreds of patients.

Hammock founded EicOsis in December 2011 to advance novel, safe and effective oral treatments for patients suffering from pain and inflammation. The LLC is developing a new class of oral non-narcotic analgesics based on inhibition of the soluble epoxide hydrolase enzyme. Human clinical trials are underway to test the drug candidate, EC5026, a first-in-class, small molecule that potently inhibits sEH. The sEH inhibitors have already shown to be effective for inflammatory and neuropathic pain in animals, with no apparent adverse or addictive reactions. 

Several grants supported the research: Dr. Bergmann received a grant from Deutsche Forschungsgemeinschaft (German Research Foundation) and a National Institutes of Health (NIH) grant from the National Institute of General Medical Sciences (NIGMS); Supp, a grant from the Shriners Hospitals for Children; and Hammock, a RIVER (Revolutionizing Innovative Visionary, Environmental Health) grant from the NIH's National Institute of Environmental Health (NIEHS), and an NIH/NIEHS Superfund Program grant. Hammock has directed the UC Davis Superfund Program for nearly four decades.

Resources:

• PNAS paper
• UC Davis distinguished professor Bruce Hammock, bdhammock@ucdavis.edu

Cindy McReynolds, a 10-year outstanding research administrator and scientist in the laboratory of UC Davis distinguished professor Bruce Hammock, Department of Entomology and Nematology--and who just received her doctorate in pharmacology/toxicology--is the recipient of the UC Davis Staff Assembly's 2021 Citation of Excellence Research Award. 

The Staff Assembly will honor her and other award recipients at a ceremony at 5 p.m., Monday, Oct. 4 at the Walter A. Buehler Alumni Center,  said Tasha Burr and Danielle Kehler, co-chairs of the Citations of Excellence Committee.  McReynolds will receive a $1500 check.   

“Our nominee, a 10-year UC Davis employee and longtime scientist with a master's degree in pharmacology and a bachelor's degree in animal science, excels at program management, research administration, and research itself,” wrote nominators Bruce Hammock, forensic entomologist Robert Kimsey and communications specialist Kathy Keatley Garvey. 

“She was the lead author of research that may be ‘the missing link' as to why some COVID-19 patients recover and some don't,” they wrote. “Her innovative work on a blood plasma biomarker discovered in hospitalized COVID-19 patients may not only predict the severity of adult respiratory distress syndrome but further research may lead to inhibiting its progression. She initiated the collaborative research to test specialized pro?resolving mediators (SPM) for their therapeutic potential against COVID-19 in a preclinical model at Rutgers University. This ongoing study is expected to provide ‘proof-of-concept' for a novel treatment to COVID-19.” 

The trio pointed out that “her  expertise includes grants management (applying and budgeting), organizing program outreach, coordinating training grants for trainees funded by a multi-million national grant, and mentoring students, whether in the lab or in the classroom. Our nominee goes above and beyond what is expected of her. Her supervisor says she is ‘the most amazing person I've ever met. For her entire career at UC Davis, she has been a phenomenal asset to the laboratory and campus.  In her role in the laboratory, she oversees an accountant who handles the complex budget problems of the federally funded UC Davis Superfund Program Project.  This multi-college, multi-principal investigator program has essentially five separate NIH grants, each of which itself is multi-departmental and multi-college supported by three cores.”

In addition, McReynolds also helped establish a community research program on human and environmental health in Northern California with the Yurok Indian Tribe, and a research translation program with several state agencies to identify STEM opportunities between UC Davis and surrounding communities.   

Coordinated National Meeting 
Hammock, who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center and for nearly four decades has directed the UC Davis Superfund Research Program (funded by the National Institutes of Health's National Institute of Environmental Health Sciences) noted that in 2019-20, McReynolds coordinated the national meeting of the Superfund Programs with multiple state and federal agencies. “She played an integral and critical role in submitting a competing renewal for years 30-35 of the program. This massive effort involved integrating multiple budgets across campus and coordinating with NIH, the campus research office, and multiple colleges.” 

“On all of these projects, her knowledge of accounting and grantsmanship, coupled with her personal skills (always congenial and eager to help) proved critical,” Hammock said. “She was involved even to the point of editing specific objectives to make the projects more integrated, which relied on her knowledge as a scientist as well.”  This was on top of being office manager for the large Hammock research laboratory involving a team of multiple disciplines. 

“During this time, she served as both the lab manager and the accountant/business manager, replacing a retiree,” Hammock noted. 

The nominators pointed out that McReynolds is a doctoral candidate (now PhD graduate), wife, mother of two, and a community volunteer. Known for sharing her scientific expertise, she organized a “Science Day” with UC Davis and Davis primary schools; organized speakers for “Meet a Scientist”; judged Davis science fairs; helped struggling high school students with their science projects; and coached the Davis Youth Robotics Team. 

“She balances her multiple difficult tasks with skill, efficiency and good humor,” the nominators wrote. “She is always eager to help, even to transporting a colleague's newly eclosed, out-of-season monarch butterfly to an overwintering site in Santa Cruz!” 

'Brilliant Researcher and Wonderful Instructor'
 Kimsey praised her work in teaching and mentoring students in his animal biology classes.  “She has not only made their time and efforts highly productive in the research arena, but provides effective counseling on their career trajectories, how to balance personal life, kids and family with university life,” Kimsey said.  “She is not only a brilliant researcher, a wonderful instructor for undergraduates that enter the laboratory, but is a dedicated and caring mentor.  Her principal investigator has stated that she is possibly the most amazing person he has ever met.  I very certainly concur in all regards.” 

McReynolds, who received her doctorate in pharmacology and toxicology in June, initially sought a career as a veterinarian. She received her bachelor's degree in animal science from UC Davis in 1999, and her master's degree in animal science from Washington State University, Pullman, in 2001. 

“After receiving a master's degree in animal science, I quickly realized that I had an interest and passion for understanding the roles of nutrition and environment on disease outcomes in both human and animal health,” McReynolds related. “Instead of continuing my research career in animal science, I left to gain experience in development therapeutics for humans and animals. My work in understanding the role of bioactive lipid mediators began in 2006 when I joined Arete Therapeutics, South San Francisco, as project manager to advance soluble epoxide inhibitors through clinical trials for treating hypertension. After leaving Arete, I joined Dr. Hammock's laboratory as a research administrator where I gained important experience in project management, budgeting and grants administration. Once my children were old enough to accommodate the often-inconsistent schedule of laboratory work, I continued my career goals of becoming a PhD scientist.” 

McReynolds traced her interest in scientific research to her “formative years in a small town in western Kentucky, cataloging observations of animals in a notebook.” 

Understanding the Roles of Lipid Mediators
McReynolds has studied the biological activity of lipid mediators for the past 12 years. “My current efforts focus on understanding the roles of lipid mediators in inflammation especially relating to pain and degenerative disease,” said McReynolds, who is a member of the American Society for Pharmacology and Experimental Therapeutics  and the American Chemical Society. “My research focuses on developing tools for use in in vitro and in vivo knockout studies to understand their role in inflammation with a focus on mechanism of pharmacokinetics.” 

McReynolds said her “career aspirations are to lead collaborative research programs that will use science to improve overall health outcomes by developing disruptive treatment or diagnostic capabilities to predict early responders/nonresponders to therapies,” she said, adding that “I approach problems and challenges now, not with a pass/fail approach, but with an understanding of how to address the problem at hand.” 

 “In my career, I strive to make significant contributions in advancing science to understand disease so that there are better treatment options for everyone; I strive to provide encouragement to women struggling to balance a family and career, to lead by example that it is possible to be a mom and scientist; I strive to motivate others, as I have been motivated by my mentors, that their fears are not too big to prevent them from reaching their goals; I strive to create a positive, collaborative work environment. Ultimately, I strive to share my enthusiasm for science and learning as well as unique background to advance a basic understanding of biology that will benefit global health outcomes for all.” 

The Staff Assembly's annual awards program provides recognition for individual staff and staff teams “who have demonstrated outstanding achievement that go above and beyond the requirements outlined in their position descriptions.” Staff Assembly presents Individual awards in the categories of innovation, research, service, supervision and teaching; and team awards for project or program staff, office staff, or other similar groups.

Resources:

• UC Davis Research: ‘Missing Link' Detected in COVID-19 Patients?
• List of UC Davis Staff Assembly's 2021 Award Winners

A newly published UC Davis research paper pinpoints what could be “the missing link” in why some COVID-19 patients recover and some don't.

A blood plasma biomarker discovered in hospitalized COVID-19 patients may not only predict the severity of adult respiratory distress syndrome (ARDS) but further research may lead to inhibiting the progression, a team of eight University of California researchers announced today.

The UC researchers, primarily from the laboratory of UC Davis distinguished professor Bruce Hammock,  found that four compounds in the blood of COVID-19 patients are highly associated with the disease. Their paper, “Plasma Linoleate Diols Are Potential Biomarkers for Severe COVID-19 Infections,” is published as open access in the current edition of Frontiers in Physiology.  

ARDS, characterized by fluid build-up in the lungs, is the second leading cause of death in COVID-19 patients, next to viral pneumonia, according to the National Center for Biotechnology Information.

“Different outcomes from COVID-19 infections are both terrifying from a human health perspective and fascinating from a research perspective,” said UC Davis lead author and doctoral candidate Cindy McReynolds of the Hammock lab. “Our data provide an important clue to help determine what impacts the severity of COVID-19 outcomes. Initially, we focused on the immune response and cytokine profile as important drivers in severity, but considering what we now know from our study and others in the field, lipid mediators may be the missing link to answering questions such as why some people are asymptomatic while others die, or why some disease resolves quickly while others suffer from long-haul COVID.” 

The compounds, known as leukotoxins and leukotoxin diols, originate from linoleic acid, the body's most abundant dietary fat, said Hammock, who holds a joint appointment in the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center and directs the National Institute of Environmental Health Sciences (NEIHS) Superfund Research Program at UC Davis. “The leukotoxins (also called EpOMEs) are converted to the leukotoxin diols (also called DiHOMES) by the soluble epoxide hydrolase we work on.”

“The hypothesis advanced in this paper is that because the leukotoxins have been associated with serious illness and death in humans and dogs and the symptoms are those of adult respiratory distress syndrome, these compounds are biomarkers of pulmonary involvement in COVID-19,” Hammock said. “We also think that it is the conversion of leukotoxin to the toxic leukotoxin diol that causes pulmonary and perivascular edema and this could be leading to the respiratory complications.”

“So the leukotoxins and leukotoxin diols,” Hammock said, “are indicators of respiratory problems in COVID-19 patients as plasma biomarkers. They also present a pathway for reducing ARDS in COVID-19 if we could inhibit the soluble epoxide hydrolase, a key regulatory enzyme involved in the metabolism of immune resolving fatty acids.”

Professor John Imig, director and eminent scholar of the Medical College of Wisconsin's Drug Discovery Center, who was not involved in the study, said: “The COVID-19 pandemic has demonstrated that coronaviruses can have deadly consequences. Lung distress is a major reason for death in COVID-19 patients infected with the coronavirus (SARS-CoV-2). The findings of McReynolds et al. identified lipids called leukotoxin diols in the blood of COVID-19 patients that could act as a biomarker for lung distress. In addition, leukotoxin diols could be responsible for lung distress in COVID-19 patients. Excitingly, this suggest that therapies to lower leukotoxin diols could treat lung distress and prevent death in COVID-19 patients.”  

“The findings presented in this paper bring important attention to a role for oxylipin metabolites in COVID-19 infections,” said Professor A. Daniel Jones of Michigan State University's Department of Biochemistry and Molecular Biology and director of the university's Research Technology Facility's Mass Spectrometry and Metabolomics Core. “Most notably, metabolites known as DiHOMEs which have been previously implicated in lung inflammation show promise for their potential to predict outcomes in COVID patients and guide therapeutic, and perhaps dietary interventions beneficial to human populations.” Jones, who was not involved in the study, serves as secretary of the Metabolomics Association of North America.  

The UC Davis scientists used clinical data collected from six patients with laboratory-confirmed SARS-CoV-2 infection and admitted to the UC Davis Medical Center, Sacramento, and 44 healthy samples carefully chosen from the healthy control arm of a recently completed clinical study.

In the introduction, the researchers wrote: “The pandemic coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), initiates an aberrant immunological response resulting in a wide range of disease severities ranging from asymptomatic cases to severe cases with rapid progression to acute respiratory distress syndrome (ARDS) and death. Patients with severe COVID-19 show evidence of hyperinflammation with increased release of inflammatory cytokines. The role of a cytokine release syndrome, or cytokine storm, in COVID-19 has drawn much attention. However, recent reports demonstrate that, although pro-inflammatory cytokine levels are elevated in severe COVID-19 patients, they are lower than levels usually observed in non-COVID ARDS, suggesting additional factors leads to severe outcomes in some patients. One of the key pathways regulating the immune response to infections is the release of regulatory lipid mediators that have dual functions of driving inflammation [e.g., prostaglandins (PGE2)] or promoting resolution of inflammation and return to homeostasis [e.g., long chain epoxy fatty acids (EpFAs)]. Recent data indicate a role of dysregulated lipid profiles in COVID-19 and identified cytochrome P450 (CYP) metabolites of polyunsaturated fatty acids (PUFA) as potential biomarkers of disease severity

The Hammock lab's 50-year research on soluble epoxide hydrolase (sEH) and its inhibitors led the professor to found and direct EicOsis Human Health, a Davis-based company that is developing a potent soluble epoxide hydrolase inhibitor for pain relief.  Epoxy fatty acids control blood pressure, fibrosis, immunity, tissue growth, depression, pain, inflammation and other processes.

But more recently, the Hammock lab has turned its attention to using sEH as a means to resolve inflammation associated with COVID-19 and the fibrosis that can follow.

Lipid metabolism researcher Ameer Taha of the UC Davis Department of Food Science and Technology pointed out that linoleic acid is an essential fatty acid present in only small amounts in our evolutionary diets. “In addition to nutritional and structural roles of linoleate, minor linoleate metabolites including the leukotoxin diols (also known as DiHOMEs) regulate a number functions including body temperature, cardiac health and vascular permeability.  This study cautions that now with dietary linoleate levels at an all-time high, in periods of high stress as with COVID-19, these regulatory functions may become detrimental.” 

The paper is the work of Hammock, McReynolds and Jun Yang of the Department of Entomology and Nematology and EicOsis Human Health; Irene Cortes-Puch of the Department of Entomology and Nematology, EicOsis Human Health, and the Department of Internal Medicine's Division of Pulmonary Critical Care and Sleep Medicine; Resmi Ravindran and Imran Khan of the Department of Pathology and Laboratory Medicine; Bruce G. Hammock of UC Davis Department of Veterinary Medicine, Aquatic Health; and Pei-an Betty Shih of the UC San Diego Department of Psychiatry. 

“This study resulted from an exciting collaboration with Imran Khan and Angela Haczku of the UC Davis School of Medicine to identify potential biomarkers for differentiating the severity of COVID-19 diseases,” said Yang, the corresponding author.

The research drew financial support from several National Institutes of Health agencies: National Institute of Environmental Health Sciences (NIEHS) Superfund Research Program and R35 grant,  National Institute of General Medical Sciences (NIGMS),and the National Institute of Mental Health (NIMH).

Resources:

• EicOsis: Developing a New Approach to Treat Pain
• Bruce Hammock:  Lifetime Achievement Award from the Chancellor 
• Cindy McReynolds Receives Major NIH Training Grant
• Cancer Team's Research Paper Named Journal of Clinical Investigation's Editor's Pick (Includes Bruce Hammock and Jun Yang)

Contacts:

• Bruce Hammock at bdhammock@ucdavis.edu 
• Cindy McReynolds at cbmcreynolds@eicosis.com or cbmcreynolds@ucdavis.edu
• Jun Yang at junyang@ucdavis.edu

 

The Food and Drug Administration has granted a fast-track designation to a non-narcotic drug candidate being developed by EicOsis LLC, a pharmaceutical company founded by UC Davis distinguished professor Bruce Hammock to treat chronic pain in humans and companion animals.

“The fast-track process is designed to facilitate the development and expedite the review of new therapies to treat an unmet medical need in the treatment of a serious condition,” said EicOsis founder and CEO Hammock, who holds a joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center.

“This designation will enable us to have early and frequent communication with the FDA throughout the drug development and review process,” Hammock said, “and this often leads to faster drug approval and patient access.”

The drug candidate, known as EC5026, targets a novel pathway to block the underlying cause of certain types of pain. Described by EicOsis, a Davis-based company, as a “novel, non-opioid and oral therapy for neuropathic and inflammatory pain,” it inhibits the soluble epoxide hydrolase (sEH) enzyme, a key regulatory enzyme involved in the metabolism of fatty acids. UC Davis recently licensed certain patents supporting the underlying technology exclusively to EicOsis.

The FDA granted EC5026, an investigational new drug (IND) clearance in October 2019. It is currently the subject of a Phase 1a clinical trial in healthy human volunteers. Phase 1b clinical trials are scheduled to begin this fall.

Earlier studies showed that the EicOsis-developed inhibitors reduce inflammatory and neuropathic pain in rodents, horses, dogs and cats, and without the addictive effects associated with opioids or multiple side effects of nonsteroidal anti-inflammatory drugs (NSAIDS).

Hammock said the successful fast-track application is the work of three EicOsis team members: clinical scientist Irene Cortés-Puch, a critical care medicine physician and researcher; project manager Cindy McReynolds, a UC Davis doctoral student in pharmacology and toxicology; and vice president of clinical development William Schmidt, who has focused his entire professional career on developing novel pain medicines.

“Without them, we would not have had the fast track,” Hammock said. “They did a superb job.”

Cortés-Puch worked in Spain in intensive care and emergency units, where she treated patients with acute respiratory distress syndrome (ARDS), and then accepted a position at the National Institutes of Health to study sepsis and ARDS, now targeted as the killer of COVID-19 patients. ARDS is respiratory failure characterized by rapid onset of widespread inflammation in the lungs.

“Listening to patient stories and working with pain management specialists has given me an understanding of the urgent need for new pain medications,” said McReynolds. “It's inspiring to work with such an amazing team in addressing this critical problem and the Fast Track status will allow us to advance this potential treatment as quickly as possible.”

Said Schmidt: “FDA's decision to grant the fast track designation to EC5026 is an important milestone in our ongoing efforts to develop a safe and effective new approach for pain management. We look forward to working closely with the FDA to optimize the development of this novel, non-opioid drug candidate for neuropathic pain.”

Dr. Scott Fishman, vice chair of the UC Davis School of Medicine's Department of Anesthesiology and Pain Medicine, who is not involved with EicOsis, commented: “It is not a coincidence that this FDA fast-track designation comes as the United States is addressing the enormous problem of opioid abuse and is seeking safer and more effective treatment for pain. This FDA designation reflects the substantial promise of this new and novel analgesic drug.”

Nearly 16 million Americans suffer from neuropathic pain, according to the National Institutes of Health (NIH). Physicians often prescribe opioids, which can lead to misuse, addiction and intolerance. Alternatively, the EicOsis drug is an effective, non-addictive drug for pain management, Hammock said.

Every day more than 130 Americans die from opioid overdose, according to the National Institute of Drug Abuse. The total economic burden of prescription opioid misuse alone in the United States is estimated at $78.5 billion a year. That includes the costs of health care, lost productivity, addiction treatment, and criminal justice involvement.

“I know my patient is suffering and sadly I know I've gone through everything available to help,” said rheumatologist Laura Carbone, professor and division chief of rheumatology in the Department of Medicine, Medical College of Georgia, Augusta University. “I struggle, we both struggle, to find a way to make today better as we both hope for something better to come that will really help. That is the daily reality of pain.” She is not involved with EicOsis.

NIH has financially supported the discovery and development of EC5026 and its advancement into clinical trials through the Blueprint Neurotherapeutics Network (BPN) of the NIH Blueprint for Neuroscience Research and the NIH's Helping to End Addiction Long-term (HEAL) Initiative.

Hammock, a member of the UC Davis faculty since 1980, received his doctorate in entomology and toxicology from UC Berkeley. Nationally recognized for his achievements, he 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.

The UC Davis professor traces the history of his enzyme research to 1969 during his graduate student days in the John Casida laboratory, UC Berkeley.  Hammock 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.”