Biochemistry Discoveries Pave Way for Therapeutics and Environmental Monitoring Tools
DERT Success Story
Bruce Hammock, Ph.D.
Renowned scientist and NIEHS grantee Bruce Hammock, Ph.D., has made groundbreaking discoveries in biology and biochemistry that have implications for improving the health of both humans and the environment. Originally trained as an insect developmental biologist, Hammock has since expanded his research into developing safe therapeutics for humans and animals, as well as developing tools to monitor exposure to environmental contaminants.
“It is fun to look back and see how this research has expanded over time,” said Hammock, who has been supported by NIEHS since obtaining his first job in 1975. “Every time we learn something new about the fundamental biology of humans and animals, it raises ten times more questions.”
Hammock directs the University of California (UC) Davis NIEHS Superfund Research Program Center, which has been funded since 1987.
Discovering a novel enzyme target
Hammock is best known for his discovery of soluble epoxide hydrolase (sEH), an enzyme in cells that degrades chemically stable fatty acid epoxides. But sometimes it can be useful to block the function of sEH, so that beneficial fatty acid epoxides, like those from omega-3 and omega-6, are not degraded. These fatty acid epoxides have been found to reduce inflammation, inflammatory pain, and even chronic or neuropathic pain.
“After we learned a bit about how the sEH enzyme works, we began to develop tools to inhibit it so we could learn more,” Hammock said. They found that the potent inhibitors could reduce inflammation and inflammatory pain in mouse and rat models more effectively than nonsteroidal anti-inflammatory drugs.
Hammock and his team found that blocking sEH after a heart attack may prevent cardiac fibrosis, scar tissue damage that often leads to heart failure, opening the doors for a new therapy to stop cardiac fibrosis. He has also found that sEH plays a key role in the inflammation associated with depression and is a potential target for treatment. He is collaborating with veterinarians to test sEH inhibitors to treat laminitis, a painful and deadly disease in horses.
More recently, Hammock and his team discovered that sEH blocks endoplasmic reticulum (ER) stress, which is a pathway that can lead to cell death. He also found that ER stress is a significant driver of neuropathic pain. According to Hammock, blocking ER stress using sEH inhibitors may be a way to control neuropathic pain, inflammatory pain, inflammation, hypertension, depression, schizophrenia, and other human diseases.
Through a small business, Eicosis LLC, Hammock is developing sEH inhibitors to treat unmet medical needs in human and animals. Through an NIEHS-funded small business grant, they are testing the safety of oral inhibitors of sEH that could be used to treat neuropathic pain in diabetic patients in Phase 1 clinical trials. Based on this support, Eicosis obtained a NIH Blueprint Development Grant. Hammock expects to have these compounds in human clinical trial early next year.
Immunoassays to detect chemicals in the environment
Hammock’s NIEHS-funded laboratory has also pioneered the use of immunoassay technologies to detect hazardous chemicals. Immunoassays use antibodies to bind to a chemical of interest, and labels on the antibodies are used to detect this binding to measure the presence and concentration of the chemical.
Hammock began this work by developing a biochemical tool to test for the presence of pyrethroids, a class of pesticides. Since then, he has developed more than 40 immunoassays for pesticides, pesticide metabolites, and other environmental contaminants. The immunoassays can be used to monitor contaminants in the environment as well as the levels that humans are exposed to contaminants using their urine.
“The immunoassays are also really useful in worker training programs,” Hammock said. “Some agricultural workers don’t realize the potential danger from exposure to pesticides. We can provide them with information about their level of exposure from their urine at the work site, which tells them whether they need to limit their exposure or use more protective equipment.”
Spanning fundamental and applied research
According to Hammock, even the most fundamental research has applications to human and environmental health. His work over the years, particularly working with sEH inhibitors, has advanced the field from both a fundamental and applied perspective.
“We started with applied research to test whether a pesticide was safe before registering it for use. It led to findings related to sEH and epoxy fatty acids that have helped us understand a variety of biological mechanisms and further understand fundamental biology,” said Hammock. “From there, we are now developing sEH inhibitors and mimics of the epoxide fatty acids as pharmaceuticals to treat veterinary and human diseases, including hypertension, depression, and neuropathic pain.”
Hammock also values the importance of engaging the community in research. He has recently initiated a project with the Yurok Tribe in northern California, training them to use immunoassays to identify and monitor exposure to environmental contaminants such as pesticides.
“People of the Yurok nation are worried about pesticide exposure from illegal marijuana growers, but they don’t want people outside of their tribe coming in and monitoring them,” said Hammock. “We are showing them how to run their own immunoassays. It is a very powerful monitoring tool that doesn’t require expensive equipment.”
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.