Hammock will present a plenary lecture on Thursday, May 31, offering an overview of the current state of the science in the area of oxidized lipids.
ISSFAL is “the leading showcase of what is new, exciting, and interesting in science and research in this field,” said executive committee member and organizing committee chair Hee Yong Kim, who serves as chief of the laboratory of Molecular Signalling for the National Institute of Health's National Institute on Alcohol Abuse and Alcoholism (NIH/NIAAA).
Hammock is known for his work on using natural chemical mediators to control inflammation and intractable pain. He continues as the founding director of the campuswide Superfund Research Program--this is the 31st year--and the NIH's National Institute of Environmental Health Sciences (NIEHS) Combined Analytical Laboratory. He has directed the NIH/ NIEHS Combined Analytical Laboratory for 25 years.
Hammock co-discovered the soluble epoxide hydrolase, and many of his more than 1100 publications and patents are on the P450 branch of the arachidonate cascade where the soluble epoxide hydrolase degrades natural analgesic and anti - inflammatory compounds. The founder of several companies, he has helped raise more than $50 million in private capital, and currently is chief executive officer of the Davis-based EicOsis, where an orally active non- addictive drug for inflammatory and neuropathic pain is being developed for human beings companion animals. EicOsis is supported by several seed-fund grants and a NIH/NINDS (National Institute of Neurological Disorders and Stroke) Blueprint Development Grant.
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 is the first McGiff Memorial Awardee in Lipid Biochemistry.
The Eicosanoid Research Foundation recently honored him for work on oxidized lipids. (See more on his website)
A newly published study by a team of university scientists in Japan, China and UC Davis shows that inhibiting an enzyme, the soluble epoxide hydrolase (sEH), plays a key role in curbing the inflammation associated with the development and progression of Parkinson's disease, an age-related brain disorder that affects a million Americans, mostly 60 and over.
The research, published today in the Proceedings of the National Academy of Sciences, is primarily the work of scientists in the labs of Kenji Hashimoto, a professor with the Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan, and Bruce Hammock, UC Davis distinguished professor of entomology with a joint appointment in the UC Davis Comprehensive Cancer Center.
“Our research suggests that the sEH inhibitor may prevent the progression of Parkinson's disease (PD) as well as treat patients with dementia of Lewy bodies (DLB) if the sEH inhibitor is used in early phases of patients with these disorders,” said Hashimoto, whose career spans 30 years in the development of blood biomarkers and novel therapeutic drugs and includes more than 550 publications on the topic. “Both PD and DLB are chronic and progressive movement disorders. However, the precise causes of these diseases are largely unknown.”
Statistics indicate physicians diagnose 60,000 new cases of Parkinson's disease every year in the United States. The average age of onset is 60, and is more predominant among men.
Hammock said that the work by lead author Qian Ren and his colleagues in the Hashimoto lab “shows that markers and symptoms of Parkinson's disease in whole mice and in human cells with a mutation associated with Parkinson's disease can be treated with a small druglike molecule. By establishing this causal chain of events leading to Lewy body disorders we can better predict environmental chemicals that could predispose people to Parkinson's disease and possibly even treat the disease.”
The paper, titled “Soluble Epoxide Hydrolase Plays a Key Role in the Pathogenesis of Parkinson's Disease,” is co-authored by 14 scientists, including Professor Hammock and Jun Yang and Sung Hee Hwang, all part of the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center.
“Although there are many medications available to treat symptoms in PD, these do not prevent the progression of the disease, and, to date, no agent with a disease-modifying or neuroprotective indication for PD has been approved,” said Hashimoto. “Therefore, the development of new drugs possessing disease-modifying and /or neuroprotective properties is critical.”
In research studies involving mice, the scientists found “that sEH plays a key role in the inflammation associated with PD pathogenesis and the mechanisms that lead to the disease,” Hashimoto said. “The sEH inhibitor or deletion of the sEH gene protected against MPTP-induced neurotoxicity in mouse brain.” MPTP is an acronym for methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine, a relative of cyperquat and paraquat herbicides. “Our findings indicate that sEH inhibitors or epoxy fatty acids mimics may be promising prophylactic or therapeutic drugs for alpha-synuclein-related neurodegenerative disorders.”
Robert Higgins, emeritus professor of neuropathology at the UC Davis School of Veterinary Medicine, said: "I find it exciting that Ren and colleagues illustrate a promising path to a drug to prevent the progression of Parkinson's disease. It is impressive how far this work has come since we collaborated with Shirley Gee and the Hammock laboratory on developing a sheep model of Parkinson's disease in the early 1980s."
Neurosurgeon Cesar Borlongan of Morsani College of Medicine, University of South Florida, who was not involved in the study, praised the findings as advancing “our understanding of how Parkinson's disease evolves.” Describing Parkinson's disease as “a devastating brain disorder that mostly affects the aging population,” he said: “There is no cure, only relief from symptoms which include tremors, muscle rigidity, slurred speech, and freezing of gait.”
“While we know that a certain group of brain cells that produce dopamine are selectively destroyed in Parkinson's patients, what triggers this brain cell death remains poorly understood,” said Borlongan, a distinguished professor and vice chair for Research, Department of Neurosurgery and Brain Repair. “In their paper, the authors observed that a protein called soluble epoxide hydrolase (sEH) may be key to the demise of the brain dopamine cells. In small and large animal models of Parkinson's disease, and further confirmed in a group of PD patients, this protein is highly elevated in specific regions of the brain implicated in dopamine cell death.”
Borlongan pointed out that “Equally compelling evidence demonstrated that using a drug that inhibits sEH can reduce brain inflammation and levels of sEH and effectively lessen PD-associated toxicity in the animal models of the disease. Clinical trials of sEH inhibitors in heart and lung disease have been ongoing over the last decade, and may facilitate the entry of these drugs for PD. These results advance our understanding of how PD may evolve, but also point to its novel treatment.”
Qing Li, a professor in the Department of Molecular Biosciences and Bioengineering, College of Tropical Agriculture and Human Resources, University of Hawaii at Mānoa, who also was not involved in the study, called Parkinson's disease “a devastating neurodegenerative disorder that affects patients and caregivers alike with a significant economic burden in the United States and worldwide.”
This basic research drew support from several grants from Japan, including the Strategic Research Program for Brain Sciences, and at UC Davis, grants funded by the National Institute of Health's Institute of Environmental Health Sciences (NIH/NIEHS), and the NIEHS Superfund Program.
Hammock, a member of the National Academy of Sciences and the National Academy of Inventors, has directed the NIH/NIEH Superfund Program for more than 30 years.
Hammock said the soluble epoxide hydrolase inhibitors that inhibit the soluble epoxide hydrolase will soon enter human clinical trials supported by the NIH-NINDS Blueprint Program (NIH's Health's National Institute of Neurological Disorders and Stroke). “These drugs could provide relief for patients with a wide variety of inflammatory diseases,” he said.
The Hammock laboratory has published nearly 900 peer-reviewed papers on the sEH enzyme, discovered while Hammock and Sarjeet Gill (now of UC Riverside) were researching insect developmental biology and green insecticides at UC Berkeley. The work, begun in 1969, led to the discovery that many regulatory molecules are controlled as much by degradation as by biosynthesis, Hammock said. These epoxy fatty acid chemical mediators control blood pressure, fibrosis, immunity, tissue growth, and pain and inflammation.
To date, journals have published more than 17,000 peer-reviewed papers on the sEH enzyme and its inhibitors. Hammock credits the NIEHS for supporting his research in this area since the 1970s.
A Davis-based company, EicOsis, is developing inhibitors to sEH
to treat unmet medical needs in humans and animals. The company recently received a multi-million dollar grant from the NIH/NINDS Blueprint Program to move sEH inhibitors through phase I human clinical trials. “We are developing a non-opiate analgesic to treat the chronic pain often associated with diabetes,” said William Schmidt, vice president of clinical development at EicOsis. “Once we have investigational new drug status from the Food and Drug Administration and have finished our phase I trial, physicians will be able initiate their own trials with the EicOsis compound on Parkinson's disease and other Lewy body disorders.”
(Embargo lifts at noon, Pacific Time, April 30)
The research, published April 30 in the Proceedings of the National Academy of Sciences, indicates that inhibiting an enzyme, soluble epoxide hydrolase--discovered in the Bruce Hammock lab at UC Davis--may reduce the risk of obesity-related inflammation of the colon.
Co-first authors Weicang Wang and Jianan Zhang of the Guodong Zhang lab, Department of Food Science, University of Massachusetts (UMass) and Jun Yang of the Hammock lab and the UC Davis Comprehensive Cancer Center, noted that 30 percent of Americans are obese, and these individuals have a 30 to 60 percent higher risk of developing colon cancer. It is the third most common cancer and the second leading cause of cancer-related deaths in the United States. Colon inflammation is an early symptom of cancer.
“But to date, the mechanisms by which obesity increases cancer risks are not well understood, and there are few effective strategies to prevent obesity-enhanced colon cancer, said co-author Guodong Zhang, a former postdoctoral researcher in the Hammock lab and now an assistant professor of food science at UMass where he focuses his research on prevention of colonic inflammation (inflammatory bowel disease) and colon cancer.
“Our study showed that soluble epoxide hydrolase and its metabolites are over-expressed in colon of obese mice,” Zhang said. “In addition, we found that pharmacological inhibition or genetic deletion of soluble epoxide hydrolase (sEH) abolishes obesity-induced inflammation and activation of pro-tumorigenic pathways in colon. These results showed that sEH is an essential enzyme involved in obesity-enhanced colonic inflammation and potentially colon cancer, and pharmacological inhibitors of sEH could be novel agents for prevention of these diseases.”
In the study, the 18-member team, including five UC Davis researchers, investigated the roles of sEH in obesity-induced colonic inflammation, which included using two different sEH inhibitors and a knockout mouse genetically modified not to produce sEH. Results proved similar in all cases.
They further conducted another study in both lean and obese mice with experimentally induced colon inflammation and used molecular analyses to follow a pathway called Wnt. About 90 percent of sporadic colorectal cancers have activating mutations within the Wnt pathway. The team found that obesity increases activation of Wnt signaling in the colon, but it can be abolished by the two different inhibitors and the knockout.
“The sEH inhibitor blocked obesity-induced colon inflammation,” said co-author Bruce Hammock, distinguished professor of entomology who holds a joint appointment with the UC Davis Comprehensive Cancer Center. “This worked even for mice on high fat diets.”
“Colon inflammation is highly associated with a variety of diseases and the inflammation often progresses to colon cancer,” Hammock said. “Weicang Wang, Guodong Zhang and co-workers have done a meticulous job investigating the biologically active fats including fatty acid diols that are associated with the inflammation. By blocking the production of these diols they were able to block the inflammation.”
Co-authors Jun Yang, Debin Wan, Jia Sun of the Hammock lab, as well as Jun-Yan Liu of China, a former postdoctoral researcher in the Hammock lab, did the analytical chemistry, and co-author Sung Hee Hwang of the Hammock lab did the organic chemistry, making the compounds that were used.Jun-Yan Liu is already collecting human samples to test the hypothesis in man, Hammock revealed.
The soluble epoxide hydrolase inhibitors that block production of these diols will soon enter human clinical trials supported by the NIH-NINDS Blueprint Program (National Institutes of Health's National Institute of Neurological Disorders and Stroke). “These drugs could provide relief for patients with a wide variety of inflammatory bowel diseases and possibly reduce obesity driven colon cancer,” Hammock said.
The team hailed this as a promising treatment in humans, but acknowledged that “mice and humans are very different.” However, Jun-Yan Liu is already collecting human samples to extend the study, and Hammock pointed out that they hope that the soluble epoxide hydrolase inhibitor will be in human clinical trials this year.
“The study was an exciting discovery from lipidomics technique,” said co-lead author Jun Yang. “The consistent results from pharmacologic inhibition and genetic knockout (KO) as well as the signaling pathway mechanistic studies all support sEH as a potential treatment for obesity- induced colon inflammation. “
Noted pathologist Guang-Yu Yang, M.D., Ph.D. of the Feinberg School of Medicine, Northwestern University, Chicago, who was not involved in the study, observed that the Zhang and Hammock labs “have now sequentially demonstrated that 1) there is an increased expression of sEH and its eicosanoid metabolites in the colons of high fat diet-induced obese mice; and 2) the knockout or inhibition of sEH ablates obesity-induced colonic inflammation and decreases obesity-induced activation of Wnt signaling. This study raises interest in further investigating whether the ablation of obesity-induced colonic inflammation by sEH knockout or inhibition may lead to inhibition of obesity-promoted colorectal carcinogenesis.”
“Thus far, non-steroidal anti-inflammatory drugs (NSAIDs) and Cyclooxygenase 2 (COX-2) inhibitor (coxibs) have been the most promising agents for the prevention of colorectal cancer,” Yang said. “However, the side effect profile and risk of adverse events including gastrointestinal (GI) bleeding and cardiovascular events frequently prohibit their widespread clinical use.”
The pathologist said that “co-targeting sEH and COX-2 to manipulate eicosanoid metabolites has the high potential to synergistically enhance the inhibition of obesity-promoted inflammation and carcinogenesis while also reducing the adverse effects of coxibs and NSAIDs.”
The five UC Davis researchers—Bruce Hammock, Jun Yang, Jia Sun, and Sung Hee Hwang and Debin Wan—are all with the Hammock lab and the UC Davis Comprehensive Cancer Center.
Other UMass researchers were Yuxin Wang, Wiepeng Qi, Haixia Yang, and Professor Yeonhwa Park, Department of Food Science, Katherine. Sanidad, Food Science and Molecular and Cellular Biology Graduate Program, and Professor Daeyoung Kim ofthe Department of Mathematics and Statistics.
The abstract: “Obesity is associated with enhanced colonic inflammation, whichis a major risk factor for colorectal cancer. Considering the obesityepidemic in Western countries, it is important to identify noveltherapeutic targets for obesity-induced colonic inflammation, todevelop targeted strategies for prevention. Eicosanoids are endogenouslipid signaling molecules involved in regulating inflammationand immune responses. Using an LC-MS/MS–based lipidomics approach,we find that obesity-induced colonic inflammation is associatedwith increased expression of soluble epoxide hydrolase (sEH)and its eicosanoid metabolites, termed fatty acid diols, in colon tissue.Furthermore,we find that pharmacological inhibition or genetic ablation of sEH reduces colonic concentrations of fatty acid diols,attenuates obesity-induced colonic inflammation, and decreasesobesity-induced activation ofWnt signaling in mice. Together, theseresults support that sEH could be a novel therapeutic target forobesity-induced colonic inflammation and associated diseases.”
This work, titled “Lipidomic Profiling Reveals Soluble Epoxide Hydrolase as a Therapeutic Target of Obesity-Induced Colonic Inflammation,” drew grant support from the USDA's National Institute for Food and Agriculture; National Institutes of Health's National Institute of Environmental HealthSciences (NIH/NIEHS); NIEHS Superfund Research Program, and the National Natural Science Foundation of China.
Hammock, a member of the National Academy of Sciences and the National Academy of Inventors, directs two major UC Davis programs; the Superfund Program financed by the National Institute of Environmental Health's National Institute of Environmental Health Sciences (NIH-NIEHS); and the NIH Biotechnology Training Program.
The Hammock laboratory has published almost 900 peer-reviewed papers on the sEH enzyme, discovered while Hammock and Sarjeet Gill (now of UC Riverside) were researching insect developmental biology and green insecticides at UC Berkeley. The work, begun in 1969, led to the discovery that many regulatory molecules are controlled as much by degradation as by biosynthesis, Hammock said. These epoxy fatty acid chemical mediators control blood pressure, fibrosis, immunity, tissue growth, and pain and inflammation.
For many years Gill and Hammock were alone in studying this enzyme but today its importance is well recognized in mammalian biology, with more than 17,000 peer-reviewed papers in the area. Hammock credits the NIEHS for supporting research in this area since the 1970s.
A Davis-based company, EicOsis, has received a large grant from the U.S. National Institutes of Health to move inhibitors to the clinic to treat diabetic neuropathic pain. “We are developing a non opiate analgesic to treat the chronic pain often associated with diabetes and hope to be in human trials over the next 12 months,” said William Schmidt, vice president of clinical development at EicOsis.
Embargo lifts at 10 a.m., Pacific Time
An inhibitor to the enzyme, soluble epoxide hydrolase (sEH), discovered in the Hammock lab, prevented the eye disease in diabetic mice, Fleming said.
The paper, “Inhibition of Soluble Epoxide Hydrolase Prevents Diabetic Retinopathy,” involving six years of research and 22 scientists, is published today (Dec. 6) in the journal Nature.
"This has been a long but exciting project where Dr. Fleming's team used tools developed to study the biology of fatty acid epoxides to probe the fundamental mechanism of diabetic retinopathy,” said co-author Hammock, a distinguished professor of entomology who holds a joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center “This work has targeted many possible sites for intervention that could preserve vision, and one such target is using inhibitors of the soluble epoxide hydrolase which block diabetic retinopathy in mice.”
The eye generates a dihydroxy metabolite from polyunsaturated fatty acids that initiates pericyte loss and breakdown of the endothelial barrier function in the eye, the scientists said. This leads to vascular edema and ultimately to a proliferation of new blood vessels and loss of vision.
The small molecule which initiates this process is a diol of a long chain poly unsaturated fatty acid produced by sEH, the researchers said. The enzyme converts an anti-inflammatory epoxy fatty acid into the pro inflammatory and in this case, toxic diol. The research team demonstrated this process and the cellular mechanism involved in diabetic mice and in transgenic mice that over-produce the sEH enzyme.
They were able to block the process by inhibiting the sEH enzyme. The expression of the sEH enzyme also increased with severity of diabetic retinopathy in human patients.
“The expression of the soluble epoxide hydrolase gene was shown to increase in the retinas of human patients with the severity of the disease with non-proliferative diabetic retinopathy,” Hammock said. “Thus, there appears a connection to human medicine.”
Diabetic retinopathy is the most common diabetic eye disease and a leading cause of adult blindness. Chronically high blood sugar from diabetes damages the tiny blood vessels in the retina, leading to diabetic retinopathy, according to the National Eye Institute (NEI) of the National Institutes of Health. The blood vessels can leak fluid or hemorrhage, distorting vision. NEI officials predict that the number of Americans with diabetic retinopathy will nearly double from 7.7 million in 2010 to 14.5 million by 2050.
Fleming said the sEH enzyme generates a toxic metabolite, but when the enzyme is inhibited, eye disease is prevented.
Earlier work reported in the Proceedings of the National Academy of Sciences from the Kip Connor laboratory at Harvard University showed that inhibiting the soluble epoxide hydrolase preserves fatty acid epoxides which reduce the late or proliferative stages of diabetic retinopathy and macular degeneration. Now the Fleming team used the same soluble epoxide hydrolase inhibitors to block production of a pro inflammatory mediator that initiates the early stages of vascular permeability and inflammation of the retina.
Connor, an assistant professor of ophthalmology at Harvard Medical School, praised the work as bringing to light ”a previously unknown mechanism of action.” Said Connor: “The identification by the laboratories of Drs. Fleming and Dr. Hammock that 19,20-dihydroxydocosapentaenoic acid, a product of soluble epoxide hydrolase (sEH) activity, as a key regulator of pericyte loss and endothelial barrier breakdown has brought to light a previously unknown mechanism of action in the induction of diabetic retinopathy. Moreover, the authors clearly show that inhibition of sEH blocks formation of this degenerative lipid metabolite thereby halting disease progression, which is of vital interest for the potential management of this blinding disease.
Mehran Moghaddam and David Grant, then with the Hammock lab, demonstrated that the diol of the fatty acid linoleate produced by the soluble epoxide hydrolase was highly toxic to cells leading to vascular permeability and sepsis. They published their work in 1997 in Nature Medicine.
"It is interesting how discoveries of years ago resurface as a critical lead in another disease indication,” commented Moghaddam. “It certainly seems hopeful we will be able to treat blindness resulting from severe diabetes."
The Hammock laboratory has published almost 900 peer-reviewed papers on the sEH enzyme, discovered while Hammock and Sarjeet Gill (now of UC Riverside) were researching insect developmental biology and green insecticides at UC Berkeley. The work, begun in 1969, led to the discovery that many regulatory molecules are controlled as much by degradation as by biosynthesis, Hammock said. These epoxy fatty acid chemical mediators control blood pressure, fibrosis, immunity, tissue growth, pain and inflammation to name a few processes, and now Fleming's team has shown the diols products from these epoxides can cause diabetic retinopathy.
For many years Gill and Hammock were alone in studying this enzyme but today its importance is well recognized in mammalian biology, with more than 17,000 peer-reviewed papers in the area. Hammock credits the National Institute of Environmental Health Sciences (NIEHS) for supporting research in this area since the 1970s.
A Davis-based company, EicOsis, has received a large grant from the U.S. National Institutes of Health to move inhibitors to the clinic to treat diabetic neuropathic pain. “We are developing a non opiate analgesic to treat the chronic pain often associated with diabetes,” said William Schmidt, vice president of clinical development at EicOsis. "It would be wonderful if the came drug also could be used to prevent the blindness driven by diabetes.
Bruce Hammock at firstname.lastname@example.org
Ingrid Fleming at Fleming@vrc.uni-frankfurt.de
Newly published research by an international team of scientists, headed by the Jun-Yan Liu lab of Tongji University, Shanghai, China, and the Bruce Hammock lab at the University of California, Davis, may provide promising therapeutic strategies for those suffering from acute kidney injury (AKI), formerly called acute renal failure.
AKI, common in hospitalized patients—especially among older adults in intensive care--occurs when the kidneys suddenly fail to filter waste products from the blood. Many of these patients do not recover or require dialysis or transplantation, or partly recover and are thus at risk for worsening kidney disease.
The paper, published in the current edition of the Proceedings of the National Academy of Sciences, found that a small molecule inhibitor of soluble epoxide hydrolase developed in the Hammock lab at UC Davis, helped alleviate AKI in mice and prolonged their lives.
“The soluble epoxide hydrolase or sEH degrades chemically stable fatty acid epoxides,” explained Hammock, a UC Davis distinguished professor who holds a joint appointment in the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. “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 fatty acids, are not degraded. These fatty acid epoxides have been found to protect the kidney, reduce inflammation, inflammatory pain, and even chronic or neuropathic pain.”
In general, the epoxides of docosahexaenoic acid (DHA) from fish oil make the soluble epoxide hydrolase inhibitors even more effective, the Hammock lab has found. “However, in this case, the fish oil seemed to be deleterious rather than beneficial when combined with the sEH inhibitors with kidney injury,” Hammock said. This was unexpected and the investigators caution that fish oil may not always have beneficial effects.
Professor Jun-Yan Liu, a former postgraduate researcher and assistant project scientist in the Hammock lab, related that the lipid mediators that preserve the kidney in AKI are termed EETs. “Their levels can be changed by altering their degradation or biosynthesis with selective inhibitors. This increase in EET resulted in anticipated decreases in the plasma level of creatinine and urea nitrogen—both biomarkers for kidney injury.” He added that they are looking forward to the epoxide hydrolase inhibitors finishing phase I clinical trials in humans so they can be evaluated for preventing or treating AKI.
Specifically, the researchers discovered that a 14(15)-EET mitigated kidney injury and prolonged life, while another epoxide, 19(20)-EDP from fish oil, exacerbated the kidney injury and shortened life. “We found that epoxides of docosahexaenoic acid (DHA) and DHA-enriched fish oil worsened kidney injury prophylactically and therapeutically in multiple animal models of AKI,” wrote Liu, pointing out that fish oil has proven beneficial in a number of other investigations.
Statistics show that “the incidence of AKI in hospitalized patients increased dramatically from 4.9 percent in 1983 to 20 percent in 2012,” the researchers wrote in their paper. “The mortality from AKI is greater than 50 percent; worldwide, approximately 2 million people die of AKI every year. Therefore, novel, safe and effective approaches are urgently needed to prevent and treat AKI.”
“Because AKI has no specific effective therapy and treatment is merely supportive frequently requiring hemodialysis any new treatment or therapeutic paradigm would be welcome in the nephrology community and has the potential to improve the lives of many patients with AKI,” said kidney expert Dr. Robert Weiss, a professor of medicine in the UC Davis Division of Nephrology, who was not involved in the research.
Kidney injury expert Alan Parrish of the University of Missouri's School of Medicine, Columbia, also not involved in the research, called the findings “significant.”
“The collaborative studies between Dr. Liu's and Hammock's group are an elegant, and timely, contribution to our understanding of acute kidney injury (AKI),” said Parrish, vice chair for education and director of Graduate Studies for Medical Pharmacology at the medical school. “AKI has potentially devastating short-term consequences - high mortality - as well as the detrimental long-term impact on renal function. Importantly, specific interventions to treat AKI in patients have not yet been identified. These results are significant in that they provide a unique mechanistic insight into pathways targeted by soluble epoxide hydrolase inhibitors that attenuate AKI, providing a powerful rationale for future clinical trials in AKI patients.”
The paper is the work of scientists led by Jun-Yan Liu from the Center for the Nephrology and Metabolomics and Division of Nephrology and Rheumatology, Tongji University School of Medicine, Shanghai, China: Bing-Qing Deng, Ying Luo, Xin Kang, Chang-Bin Li, Jian Huang, Da-Yong Hu, Ming-Yu Wu, and Ai Peng; and Hammock and his lab researchers Jun Yang, Christophe Morrisseau, Kin Sing Stephen Lee at UC Davis.