Researchers at the Huazhong University of Science and Technology, Wuhan China, used the drug developed at UC Davis to show that the neurofibrillary pathology of an Alzheimer's disease-related protein could be dramatically reduced. Their work was published in December in the Journal of Huazhong University of Science and Technology.
“They further demonstrated the mechanism of action of the UC Davis drug in blocking the oxidative stress-driven phosphorylation events associated with Alzheimer's disease,” Hammock said. The UC Davis drug stabilizes natural anti-inflammatory mediators by inhibiting an enzyme called soluble epoxide hydrolase (sEH) discovered at UC Davis and recently spotlighted in the Proceedings of the National Academy of Sciences and the National Institutes of Health's PubMed.
“I was thrilled to see this paper on tau phosphorylation from Huazhong University shows that our drug could block a key event and a key enzyme called GSK-3 beta thought critical in the development of Alzheimer's disease,” said Hammock, who holds a joint appointment in the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center.
“We were planning to do this study, but having another laboratory do it with our compound was even better,” he said. “Since our publication last year in PNAS that showed UC Davis soluble epoxide hydrolase inhibitors both prevented and reversed depression, we have been excited about trying to block the development of Alzheimer's disease.”
The PNAS paper, “Gene Deficiency and Pharmacological Inhibition of Soluble Epoxide Hydrolase Confers Resilience to Repeated Social Defeat Stress,” was co-authored by a 13-member research team led by Hammock and Kenji Hashimoto of Chiba University Center's Division of Clinical Neuroscience, Japan. They found that sEH plays a key role in the pathophysiology of depression, and that epoxy fatty acids, their mimics, as well as sEH inhibitors could be potential therapeutic or prophylactic drugs for depression and several other disorders of the central nervous system. Co-authors of the paper included Hammock lab researchers Christophe Morisseau, Jun Yang and Karen Wagner.
Hammock credited several UC Davis colleagues for their work leading to the publications. Research from the labs of Liang Zhang and Qing Li at the University of Hawaii--Qing is a former UC Davis doctoral student--pointed out some of the mechanisms involved in cognitive decline which associate professor Aldrin Gomes of the UC Davis Department of Neurobiology, Physiology and Behavior and Fawaz Haj of the UC Davis Department of Nutrition “have shown to be blocked by the natural metabolites stabilized by the UC Davis drugs,” Hammock said.
One of the Hammock lab drugs is moving toward human clinical trials for neuropathic pain through a Davis-based company, EicOsis, LLC, and the financial support of the Blueprint Program through NIH's National Institute of Neurological Disorders and Stroke. Hammock founded the company to develop inhibitors to the soluble epoxide hydrolase, a key regulatory enzyme involved in the metabolism of fatty acids, to treat unmet medical needs in human and animals.
“The clinical back-up candidate at EicOsis penetrates the blood brain barrier and should be a perfect compound to test if this class of chemistry can prevent cognitive decline and Alzheimer's disease,” Hammock said.
The National Institute of Environmental Health Sciences, National Institutes of Health, funded the research.
Highly honored by his peers, 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 the Bernard B. Brodie Award in Drug Metabolism, sponsored by the America Society for Pharmacology and Experimental Therapeutics. He 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.
Xu, professor of agro-ecology at the China Agricultural University (CAU), is on a yearlong sabbatical in the Hammock lab. He received assistance in obtaining the grant from project manager Bruce Hammock and program manager Shirley Gee, now retired, both co-investigators.
“This is a highly competitive program and this grant is a huge honor for Ting and for Shirley Gee,” said Hammock, who holds joint appointments in the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Center.
The $330,000 grant, funded by China, is a cooperative agreement between UC Davis and China. “The grant is quite timely, as UC Davis is working to increase scientific exchange with China,” Hammock said. “We have been collaborating with Ting's group for several years on nanobody-based immunoassays to improve human and environmental health.”
Two previous students from Professor Xu's laboratory have studied in Davis and the funds will allow additional senior Ph.D. students from Xu's laboratory to join the Hammock lab.
Xu described immunoassays as “a rapid, sensitive and cost effective method of analysis for pesticides.” Technically, engineering antibodies “such as a variable domain of heavy chain antibody (VHH) from camelids and a single-chain antibody variable fragment (scFv) from chickens have advantages over monoclonal and polyclonal antibodies in the respect of small size, thermal stability, solubility and easy generation,” Xu explained. “The objectives of this project focus on the production of specific VHHs and scFvs for several pesticides and the development of engineering antibodies based immunoassays for pesticide environmental exposure and food safety. The novel pesticide antibodies are expected to improve the assay sensitivity and stability.”
“Nanobodies are revolutionizing immunoassay development and possibly disease therapy,” explained Shirley Gee, UC Davis collaborator on the proposal. “It was thrilling over the last few months to have Ting and his student here at the same time as Gualberto Gonzalez from Uruguay and his students since we are three of the major labs developing this technology for analyzing environmental and food toxins.”
Among other benefits, the research can aid farm workers, who would be monitored for pesticides in their urine. The assay could distinguish between exposed and unexposed populations and provide useful information about relative exposure related to crop or use of personal protective equipment.
Xu's publications directly address the fact that the immunoassay method, especially ELISA, is an effective screen tool for the agrochemicals and pollutants in the environment. His main contributions to science are associated with design of novel haptens, production of tradition (monoclonal and polyclonal) and engineering antibodies, and development of competitive and non-competitive enzyme-linked immunosorbent assays (ELISA) for small molecules.
Xu received his doctorate in agro-ecology in 2003 from CAU, and did postdoctoral research in immunoassays in 2007 at the University of Hawaii. He joined the CAU faculty in 2003 as a lecturer and advanced to associate professor in 2007, and professor in 2013. Twice honored by Chinese governments, Xu received third prize for the Agriculture Science and Technology Award by the China Ministry of Agriculture in 2009, and second prize for the Technological Invention Award by the China Ministry of Education in 2013.
“We think that this research will lead to a very positive outcome to improve the lives of cystic fibrosis patients,” said co-author Bruce Hammock, distinguished professor in the UC Davis Department of Entomology and Nematology who holds a joint appointment with the UC Davis Comprehensive Cancer Center.
The research, published in the current edition of the Proceedings of the National Academy of Sciences, links a newly discovered class of bacterial enzymes to battling cystic fibrosis, a progressive, genetic disease characterized by persistent lung infections and inability to breathe normally.
Senior author Jennifer Bomberger of the Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine explained that the opportunistic bacterium, Pseudomonas aeruginosa, outcompetes other microorganisms in a cystic fibrosis patient's lungs and establishes a stronghold.
The scientific discovery could lead to new therapies that would interrupt or correct the bacterial sabotage, Hammock and Bomberger said.
“This paper is the outcome of an exciting and interdisciplinary project,” said Hammock, who directs the UC Davis Superfund Program financed by the National Institutes of Health's National Institute of Environmental Health Sciences (NIH-NIEHS).
“It started several years ago with the NIEHS Superfund Program funding both a group at Dartmouth and at UC Davis. A very productive and exciting collaboration resulted in looking at how to mitigate the effects of environmental chemicals on human health. Our collaborative work led to this joint publication which yields exciting hope for cystic fibrosis patients.”
Bomberger continues to work on the biology of the system while the Dartmouth and Davis groups have developed inhibitors of the action of CIF to stabilize pro-resolving mediators, reduce inflammation, and control periodic flare ups of bacterial infections.
"It will be key to devise a way to remove P. aeruginosa's ability to capitalize on the body's natural inflammatory response, without eliminating that response," said Bomberger. "Inflammation is happening for a reason—to clear infection. We just need it to temper the response when it is not effectively doing its job or is no longer needed."
Other co-authors of the paper include Hammock lab members Christophe Morisseau and Jun Yang, both from the UC Davis Department of Entomology and Nematology and UC Davis Comprehensive Cancer Center. .Institutions involved in the study also included the Harvard School of Medicine.
Bruce Hammock, director of the UC Davis Superfund Program, learned of the notable achievement at the directors' meeting Dec 5-8 in Durham, N.C.
"The productivity of the next two most productive programs combined, do not match that of UC Davis,” said (in jest) Hammock, distinguished professor in the Department of Entomology and Nematology who holds a joint appointment with the UC Davis Comprehensive Cancer Center.
UC Davis Superfund co-director Tom Young, professor of civil and environmental engineering, College of Engineering, quipped that UC Davis faculty will need bodyguards now if they are around the other programs.
Hammock credited the productivity to “great students and postdoctoral fellows and wonderful senior scientists,” but added that “we must not overlook executive administrative assistant Louisa Lo; UC Davis Superfund program manager Sukhi Aujla; and Hammock lab program manager Cindy McReynolds who ensured that the papers were filled correctly with NIH.”
The NIH NIEHS Superfund Research Program at UC Davis, funded for 30 years, has brought almost $100 million to the campus to study how to evaluate the risk of environmental chemicals as well as to remediate toxic waste sites.
Dr. Goodrow joined the environmental diagnostics group in the Entomology Department and participated in the inaugural UC Davis/National Institute of Environmental Sciences (NIEHS) Superfund Research and Training Program, an interdisciplinary program directed by Bruce Hammock, distinguished professor in the Department of Entomology and Nematology. The program was formed 30 years ago.
“Marvin was proud to have worked with Donald Cram who won the Nobel Prize in 1987,” Hammock recalled. “He carried out key organic chemistry for preparation of numerous immunoassays for pesticides and other environmental contaminants. He was an enthusiastic mentor of young scientists.”
In addition to his research with the Superfund Program, Goodrow worked with the National Institute for Occupational Safety and Health (NIOSH) Farm Worker Health Program.
“Marvin also provided support for the synthesis of soluble epoxide hydrolase inhibitors at the beginning of the urea project; his compounds were key for early SAR (structural-activity relationship) on sEH inhibition,” said Christophe Morisseau, a researcher in the Hammock lab.
Dr. Goodrow's family recalled that “he utilized his free time to pursue his passion as a research chemist at UC Davis, where he participated in a superfund research program.” His work was published in numerous professional journals, including the Journal of Organic Chemistry.
Born in San Fernando Valley on Sept. 27, 1930, Marvin received a bachelor's degree in chemistry from Pomona College, Claremont, and a doctorate in organic chemistry from UCLA. He served as a teaching assistant in organic chemistry at UCLA and an instructor at University of Michigan, Ann Arbor. In 1964, he relocated to Modesto, and worked as a research chemist for Shell Development Company. In 1968 he joined the Modesto Junior College as a chemistry instructor, retiring in 1991.
Dr. Goodrow was a member of the American Chemical Society, Alpha Chi Sigma, a chemistry and engineering professional fraternity, and Phi Lambda Upsilon, a chemistry honor society.
He was the son of the late Cecil and Dorothy Goodrow, and husband of the late Virginia Goodrow. He is survived by his son and daughter, Jonathan and Elizabeth Goodrow;his brother, Richard Goodrow and numerous nieces and nephews
A funeral service was held Wednesday, Oct. 5, at Park View Cemetery, Manteca.