- Author: Kathy Keatley Garvey
The award consists of a $2,000 honorarium and a commemorative medal. His work will be published in the journal Drug Metabolism and Disposition.
A member of the UC Davis faculty since 1980, Hammock will receive the award April 28 during the joint annual meeting of the ASPET and the Chinese Pharmacological Society, set for April 26-30 in San Diego. He will present a keynote speech about his research.
The award recognizes Hammock’s outstanding original research contributions to the understanding of human drug metabolism and transport and the continued impact of his research in the area of drug discovery and development.
Hammock, who directs a laboratory of more than 40 scientists and students in the UC Davis Department of Entomology and Nematology, explores the biochemical basis of human and environment interactions and their implications for improving both human and environmental health.
For more than 35 years, Hammock has worked on the mechanism of certain hydrolytic enzymes and their effect on human health. 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.
In selecting Hammock, ASPET acknowledged Hammock’s collaborative studies in drug metabolism and metabolomics. The society also noted his tradition of sharing reagents for research to enable investigators in both the private and public sectors to make substantial advances for the development of potentially useful therapeutic compounds to treat stroke, atherosclerosis, heart failure, renal failure, inflammation and neuropathic pain.
Hammock is best known for his work on epoxide hydrolases and in particular, the soluble epoxide hydrolase (sEH), but also has made major contributions to the esterase field and other enzymes involved in drug metabolism. He has received many awards for his work in agriculture, toxicology and chemistry.
Hammock 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. He is a fellow of the Entomological Society of America, a member of the prestigious National Academy of Sciences, and the recipient of the 2001 UC Davis Faculty Research Lecture Award and the 2008 Distinguished Teaching Award for Graduate and Professional Teaching.
Hammock 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.
KEY DISCOVERIES ON sEH FROM HAMMOCK LABORATORY
- Discovery of sEH (1972)
- First rapid radiochemical assay methods (1979, 1980)
- First spectral and fluorescent assays for the enzyme (1982, 1988, 1994)
- Fluorescent high throughput assay for screening (2005, 2006)
- First high throughput screen (90,000 compound National Institutes of Health library) (2007, PubChem)
- Initial determination of substrate selectivity (1979, 1980)
- Discovery that fatty acid epoxides are good substrates for sEH (1979)
- Discovery that PPAR alpha agonists induce the sEH (1983)
- Development of first antibodies to sEH (1981)
- Development of 1 step affinity purification procedure for sEH (1985, 1988)
- Cloning and expression of rodent and human sEH cDNA (1993)
- First cloning, expression and characterization of a plant sEH (1994)
- Cloning of first sEH gene (1994)
- First irreversible inhibitors (1982)
- Discovery that arachidonate epoxides are substrates of sEH (1983)
- First study of regio and stereospecificity of enzyme (1980, 1993)
- Regio and enantiospecificity of sEH with epoxyeicosanoids (1993)
- First isolation of substrate-enzyme complex (1994)
- Elucidation of the catalytic mechanism of epoxide hydrolases (1995)
- Discovery that linoleate diols are chemical mediators (1997)
- Blocking linoleate epoxide toxicity with EH inhibitors (1998)
- X-ray structure of the sEH (1999)
- Discovery of first transition state mimics of EH (1999)
- Reduction of blood pressure in vivo with sEH inhibitors (sEHI) (2000)
- Development of the first potent mEH inhibitors (2001)
- Characterization of eicosanoid profiles by LC-MS including EETs (2002)
- Demonstration that sEH is a divalent enzyme with lipid phosphatase activity (2003)
- Demonstration that sEHI can treat rodent models of chronic pulmonary obstructive disease (copd) and lipopolysaccharide induced sepsis (2005)
- Demonstration that sEHI shift the entire arachidonate cascade from a pattern of initiation of inflammation to a pattern of resolution of inflammation (2005)
- Founded a company and acquired funding to develop sEHI clinically (2005)
- Demonstrated sEHI synergize COX inhibitors and reduce thromboxanes (2006)
- Optimized picomolar sEHI with good ADME in rodent, canine and primates (2007)
- Demonstration sEHI synergize LOX and FLAP inhibitors (2007)
- Demonstration sEHI are strongly analgesic (2007)
- Demonstration that sEHI are strongly analgesic with neuropathic pain (2008)
- Successful treatment of diabetic neuropathic pain with sEH inhibitor in double blind cross over trial (2012)
- Demonstration that the ω-3 epoxide, DHA, is more potent at reducing blood pressure, pain, and inflammation than ω-6 ARA (2011-13)
- Demonstration that DHA epoxide reduces angiogenesis, tumor growth and metastasis (2013)
- The sEHI and other compounds from the Hammock laboratory have been used to dissect the basic biology of the P450 branch of the arachidonate cascade and to identify numerous clinical targets ranging from cardiovascular disease to diabetes.
ASPET is a 4800-member scientific society whose members conduct basic and clinical pharmacological research in academia, industry and the government. Their efforts help develop new medicines and therapeutic agents to fight existing and emerging diseases.
Last year’s Brodie Award recipient was Yuichi Sugiyama of the University of Tokyo, a world leader in the pharmacological and pharmaceutical sciences via integrative studies on the pharmacokinetics and membrane transport of drugs.