NIEHS grantee Bruce Hammock, Ph.D., a toxicologist and entomologist at the University of California, Davis (UCD), is the first recipient of the John C. McGiff Memorial Award for Contributions to Eicosanoid Research. Eicosanoids are cellular compounds derived from polyunsaturated fatty acids and are important in a number of body processes.
NIEHS Scientific Director Darryl Zeldin, M.D., presented the award during the March 13-16
International Winter Eicosanoid Conference in Baltimore. The conference is supported in part by NIEHS. “He has been a leader in the eicosanoid research community, and an outstanding collaborator and colleague,” said Zeldin, one of the conference organizers.
Many common medications, including over-the-counter painkillers and anti-inflammatory drugs, work by altering eicosanoid pathways. By focusing on specific steps in the eicosanoid pathway, Hammock’s team has identified therapeutic compounds that block the processes involved in hypertension, pain, and inflammation.
As part of the award, Hammock presented the McGiff Memorial Lecture, titled “Epoxide Hydrolase Inhibitors as Biochemical Probes and Drug Candidates.”
“We found that some of our compounds reach the brain where they can reduce complications from stroke and convulsions, including those from epilepsy,” he noted. “Based on these brain-penetrating compounds, Kenji Hashimoto’s lab at the Chiba University Center for Forensic Mental Health, Japan, found that they are promising for depression, bipolar disorders, and some other central nervous system effects.” (See text box.)
Hammock has received individual research grants from NIEHS and is the lead researcher in the NIEHS-funded Superfund Research Program (SRP) Center at UCD. He is a fellow of the National Academy of Inventors, a member of the National Academy of Sciences, and recipient of many other awards, including the Bernard Brodie Award in Drug Metabolism, an NIEHS Merit Award, and the Kenneth A. Spencer Award in Agricultural Chemistry. Hammock is a distinguished professor of entomology and holds a joint appointment with the university’s comprehensive Cancer Center.
(This story is based on a UCD
press release by Kathy Keatley Garvey.)
Chemical shows promise for treating depression and inflammation
By Kelly Lenox
Findings reported March 14 by Hammock and collaborators suggested that soluble epoxy hydrolase (sEH) plays a key role in the inflammation associated with depression and is a potential target for treatment. Depression is a severe and chronic psychiatric disease that affects 350 million people around the world, the authors noted.
Hammock and his team at UCD worked with a team in Japan led by Kenji Hashimoto, Ph.D., of Chiba University, to study a mouse model for a form of depression known as social defeat stress. The authors highlighted several important conclusions.
- A single dose of a potent sEH inhibitor known as TPPU can produce a rapid antidepressant effect in the inflammation and social defeat stress models of depression.
- The scientists uncovered particular molecular signaling in the prefrontal cortex and hippocampus regions of the brain associated with stress resilience.
- sEH inhibitors appear to lack the potential for abuse and certain side effects exhibited by ketamine, a substance that also exhibits rapid antidepressant effects.
“These findings suggest that sEH inhibitors have the ability to be more effective, faster acting, and have fewer side effects than current antidepressant drugs,” the authors wrote.
The researchers also reported that in the brains of mice that were chronically stressed, as well as in the postmortem brain samples of patients with psychiatric diseases, expression of genes that code for the sEH protein was higher than that in controls.
“The effects of exposures on sEH activity are complex,” said David Balshaw, Ph.D., head of the NIEHS Exposure, Response, and Technology Branch. “Bruce’s research into the basic biochemistry of sEH has helped us understand those interactions and how they may underlie not only mental health but also several other areas, from pain to atherosclerosis to kidney disease.”
Funding for the study included a research grant to Hammock, SRP Center funding, as well as other support from the National Institutes of Health and Japanese sources.
Ren Q, Ma M, Ishima T, Morisseau C, Yang J, Wagner KM, Zhang JC, Yang C, Yao W, Dong C, Han M, Hammock BD, Hashimoto K. 2016. Gene deficiency and pharmacological inhibition of soluble epoxide hydrolase confers resilience to repeated social defeat stress. Proc Natl Acad Sci U S A; doi:10.1073/pnas.1601532113. [Online 14 Mar 2016].