- Author: Kathy Keatley Garvey
Have you heard about the entomologist who went from researching venomous scorpions to alleviating human neuropathic pain?
That would be Bora Inceoglu, who holds a doctorate in entomology from the University of California, Davis. He and five colleagues were recently informed that their groundbreaking research on neuropathic pain made Discover magazine's Top 100 Science Stories of 2015. In fact, the research ranks among the Top 15 in the Medicine/Genetics category.
The Proceedings of the National Academy of Sciences published the UC Davis research, “Endoplasmic Reticulum Stress in the Peripheral Nervous System is a Significant Driver of Neuropathic Pain,” in July 2015. (See UC Davis news story)
Inceoglu, a researcher in the Bruce Hammock lab, UC Davis Department of Entomology and Nematology/UC Davis Comprehensive Cancer Center, and Ahmed Bettaieb, then of the Fawaz Haj lab, Department of Nutrition, served as the lead researchers. The six-member team, in addition to Inceoglu, Bettaieb, Haj, and Hammock, included K.S. Lee and Carlos Trindade da Silva, both of the Department of Entomology and Nematology/UC Davis Comprehensive Cancer Center.
They pinpointed the key mechanism that causes neuropathic pain--a complex, chronic and difficult-to-treat pain caused by nerve injuries from trauma or from such diseases as diabetes, shingles, multiple sclerosis and stroke.
Discover magazine headlined its story on the UC Davis research: “A Key Piece of the Pain Puzzle Is Solved.” Writer Heather Stringer quoted Hammock as saying: “Medications have historically focused on turning down the nerve response to pain, but now we've found one way to block the stress signal that generates the pain.
“Most of us probably take for granted that physical pain—whether it be from a sports injury, a kidney stone or appendicitis—can be attributed to some form of inflammation and that it will end,” Stringer wrote.
“Neuropathic pain, however, affords its sufferers no such luxuries,” Stringer pointed out. “It's chronic and unrelenting, and its cause is unknown, making treatment difficult. It turns out that neuropathic pain is triggered when the body experiences endoplasmic reticulum (ER) stress, a condition in which the production and transport of protein exceeds the cells' capacities, say researchers from the University of California, Davis. Because diabetics are at high risk of having neuropathic pain, the team studied diabetic rats that had neuropathic symptoms: hypersensitivity to touch and lack of heat sensation. And the rats' nerve cells showed clear signs of ER stress.”
“When the researchers treated the rats with a compound that blocks ER stress, the pain symptoms disappeared. Conversely, healthy rats developed neuropathy when they received chemicals that induce the stress response.”
How It All Began
Hammock discovered a human enzyme termed sEH which regulates a new class of natural chemical mediators. He and his lab then developed inhibitors of the sEH enzyme which degrades natural mediators reducing hypertension, inflammation and pain.
Recently he founded the company, Eicosis LLC, to target diabetic neuropathic pain. The company just received two large federal grants for translational drug development and aims to move one of the sEH inhibitors to human clinical trials.
Hammock, who holds a doctorate in entomology/toxicology from UC Berkeley in 1973, joined the UC Davis entomology faculty in 1980. He is a member of the National Academy of Sciences and a fellow of the National Academy of Inventors. The Hammock lab is the 30-year home of the UC Davis/NIEHS Superfund Research and Training Program, an interdisciplinary program funded by the National Institute of Environmental Sciences (NIEHS) that has brought in almost $60 million to the UC Davis campus. The Hammock lab is also the home of the NIH Training Grant in Biomolecular Technology. The lab alumni, totaling more than 100 graduates, hold positions of distinction in academia, industry and government as well as over 300 postdoctorates.
From Insects to Humans
How did Bora Inceoglu move from entomology to neuropathic pain?
"As most kids I found insect fascinating from the start, little machines that could do so much," he said. "As an undergraduate, I studied plant protection. Half of the curriculum was basic and applied entomology, the other half being plant pathology and weed science. Therefore, my college degree was mostly based on pest management and I found insecticide resistance most interesting. This was the impetus for seeking an advanced degree in this area."
Inceoglu was awarded two separate scholarships to study insecticide resistance in the U.S. His research of prominent laboratories in this area landed him in the Hammock laboratory in 1996. "Bruce was my major professor and I completed my Ph.D. in his laboratory in 2002," Inceoglu said. "My thesis was isolation and characterization of insect selective toxins from the venom of scorpions and Dr. Hammock had just received a sizable sample of venom of a South African scorpion, well known for its highly toxic properties. The insect selective toxins were highly sought after at the time because Dr. Hammock developed the technology to engineer these small peptides into the genome of an insect selective virus, a baculovirus. The genetically modified baculoviruses are much faster in killing the pest insects owing to the toxin being produced as the virus infects the host larvae and replicates within."
"Although unexpected, when I started characterizing the new venom we had, we found no insect selective peptide toxins in it," Inceoglou recalled. "Instead we identified a whole new class of peptides that affect mammalian ion channels." To make his work easier, he tried and obtained the live scorpion specimens imported from South Africa. "I do not think they are available for sale now but at the time I was able to get together a few dozens of these animals. I periodically milked the venom from these scorpions which enabled me to have a consistent supply of venom. "
And today?
"Currently we are not working on scorpion venoms," Inceoglu says, "but the technology developed by Dr. Hammock remains as one of the more innovative approaches to pest control."
Meanwhile, neuropathic pain research emanating from UC Davis continues to be spotlighted, as well it should be. It affects some 100 million Americans alone, but even more worldwide.
- Discover Magazine 100 Top Stories of 2015
- Discover Magazine: Key Piece of the Pain Puzzle Is Solved
- PNAS article
- UC Davis News Story: Groundbreaking Research on Neuropathic Pain
- Faculty 1000 Honor
- Author: Kathy Keatley Garvey
He's an entomologist, trained to find ways to control insect pests, but now he aims to help humans with medical issues, including diabetes, high blood pressure and depression.
Bruce Hammock, distinguished professor of entomology at UC Davis, has just received the international John C. McGiff Memorial Award for his pioneering contributions to eicosanoid research.
The average person on the street probably has no clue what eicosanoids are. Well, as Hammock explains: "Eicosanoids are a particular class of fats that, rather than being nutritional or structural, are regulatory. They regulate blood pressure, childbirth, pain, inflammation, tissue repair and other biologies. By mass, more than 75 percent of the world's medications work on the eicosanoid pathway. These include such familiar drugs as aspirin, Advil, Ibuprofin and Motrin."
Hammock, who holds a joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center, received the award during the International Winder Eicosanoid (WEC) Conference, March 13-16 in Baltimore, Md. He delivered the McGiff Memorial Lecture on “Epoxide Hydrolase Inhibitors as Biochemical Probes and Drug Candidates.”
“The current drugs that alter the eicosanoid pathways block the formation of drugs that block natural fats that increase hypertension, increase pain and increase inflammation,” Hammock explained. “We have been working on a third branch of the pathway that reduces blood pressure, inflammation and pain. By blocking the degradation of these natural molecules we block harmful biologies. These new drugs are promising for control of diabetes, hypertension and other diseases. We are working to move some of these compounds that work outside of the brain to the clinic for both man and companion animals to control inflammatory and chronic pain.”
"However, we found that some of our compounds reach the brain where they can reduce complications from stroke and convulsions, including those from epilepsy. 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. These compounds have proven valuable to numerous investigators to understand disease biology and are being followed by several drug companies.”
Using the newly discovered chemical in the Hammock lab, the UC Davis and Hashimoto researchers drew international attention on March 14 for their publication in the Proceedings of the National Academy of Sciences (PNAS). The result could be a new, innovative tool to control depression, a severe and chronic disease that affects 350 million persons worldwide, they said.
“The research in animal models of depression suggests that sEH plays a key role in modulating inflammation, which is involved in depression,” according to the UC Davis-issued news release. “Inhibitors of sEH protect natural lipids in the brain that reduce inflammation, and neuropathic pain. Thus, these inhibitors could be potential therapeutic drugs for depression.”
WEC is a group of scientists who have high standards of research, but freely collaborate and exchange reagents and ideas. It represents science at its best. "Never would we have made the advances we have at Davis without this friendship and collaboration of scientists from around the world,” Hammock said. This year's conference drew 150 scientists.
Bruce Hammock, who received his doctorate in entomology/toxicology from UC Berkeley in 1973, joined the UC Davis entomology faculty in 1980. With Sarjeet Gill (now at UC Riverside) he discovered that the enzyme, soluble epoxide hydrolase (sEH), degrades fatty acid epoxides and plays an important role in human diseases. He and his lab have developed inhibitors of sEH that are anti-inflammatory, anti-hypertensive, analgesic and organ-protective. Recently he founded the company, Eicosis LLC, to target diabetic neuropathic pain. The company just received two large federal grants for translational drug development and aims to move one of the sEH inhibitors to human clinical trials.
The Hammock lab is the 30-year home of the UC Davis/NIEHS Superfund Research and Training Program, an interdisciplinary program funded by the National Institute of Environmental Sciences (NIEHS) that has brought in almost $60 million to the UC Davis campus. The Hammock lab is also the home of the NIH Training Grant in Biomolecular Technology. The lab alumni, totaling more than 100 graduates, hold positions of distinction in academia, industry and government as well as over 300 postdoctorals.
The UC Davis distinguished professor has authored or co-authored more than 1020 peer-reviewed publications, many in top journals. This includes 500 related to epoxide hydrolase, 80 related to esterase and amidase, more than 260 related to immunoassay, and 240 related to insect biology.
Hammock is a fellow of the National Academy of Inventors (NAI), which honors academic invention and encourages translations of inventions to benefit society. He is a member of the National Academy of Sciences (NAS) and the recipient of numerous other awards, including major teaching awards at UC Davis.
And yes, he's an entomologist. He's a fellow of the Entomological Society of America (ESA) and recipient of the ESA's Recognition Award for Insect Physiology, Biochemistry and Toxicology.
Bruce Hammock: from six-legged insect pests to two-legged Homo sapiens.
- Author: Kathy Keatley Garvey
Disheveled and depressed. Desolate and defeated. Weary and worn.
Is that really Bruce Hammock, the distinguished professor who holds a joint appointment in the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center?
It is.
He and his wife, Lassie, portray cameo roles as drought-ravaged farmers in the newly released indie, The Last Survivors, directed by their son, Tom Hammock. Starring Jon Gries, Haley Lu Richardson and Booboo Stewart, The Last Survivors has been described as a low-budget cross between Mad Max and The Hunger Games. (See trailer on YouTube)
And where are Bruce and Lassie Hammock in the film? They're in the grave-digging scene. They're standing at the back, Bruce comforting his wife as they mourn the death of a fellow farmer and worry about their future.
The official synopsis: "At the edge of an expansive barren valley, all that remains of The Wallace Farm for Wayward Youth is a few hollowed-out husks of buildings. Seventeen- year-old Kendal (Haley Lu Richardson) can barely recall when the Oregon valley was still lush. It's been a decade since the last rainfall, and society at large has dried up and blown away. Kendal and the few others that remain barely scrape by while dreaming of escape. When a greedy water baron lays claim to what little of the precious resource remains underground, Kendal must decide whether to run and hide or bravely fight for the few cherished people and things she has left. Co-starring Booboo Stewart (The Twilight Saga), Max Charles (The Amazing Spider-Man, Mr. Peabody & Sherman) and genre veteran Barbara Crampton (You're Next, Re-Animator), The Last Survivors is a suspenseful look at a futuristic world where only the most resourceful survive.."
For The Last Survivors, Director Tom Hammock asked both his parents and brother Bruce to serve in cameo roles. The younger Bruce, a postdoctoral researcher working on insect ecology in the UC Davis School of Veterinary Medicine, plays a "bad guy on a water truck."
Professor Bruce Hammock is better known in academic and administrative circles as the director of 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 just recently formed the company, EicOsis LLC, to target neuropathic and inflammatory pain and received a $4 million federal grant to advance his compound discovery through Phase 1 clinical trials. He is a fellow of the National Academy of Inventors, 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. He's also an athlete who engages in white-water rafting and hiking.
Here at UC Davis, we call Bruce Hammock "The Genius." That's because he is. And now, he's an actor.
For the December 2013 shoot in the Mojave Desert (meant to depict a drought apocalypse in Oregon), the professor grew a beard, donned his father's old ragged World War II clothes and worn-out shoes, and practiced looking forlorn and haggard.
How would he describe his future in acting? "Brief and undistinguished," he joked, adding
The Last Survivors, initially named The Well, is getting a lot of play. It's now on Showtime, Netflix and Amazon.
The crew worked hard, Bruce Hammock recalled. “We were on the set at 5:30 a.m. We worked until dark, in weather well below freezing, with high winds blowing sand. The professional actors and actresses put in amazing performances under quite adverse conditions. They're a very professional and fun group. I had never realized the complexity of filming a movie. I hope they pull off their vision.”
Son Tom Hammock initially thought of becoming a biologist. A 1994 graduate of Davis High School, he studied biology at UC Berkeley, and then switched to landscape architecture. After receiving his bachelor's degree in landscape architecture, he headed off to the American Film Institute to study film design. His credits including serving as the production designer for the critically acclaimed horror films, All the Boys Love Mandy Lane and You're Next, and working on such film productions as Breaking Bad, Dexter, and Charlie and the Chocolate Factory. He is now very much involved in the hugely popular young adult and horror film genre, but showed more of his talent when he authored the original graphic novel, “An Aurora Grimeon Story—Will O' the Wisp." (See previous Bug Squad blog)
Warning: Before you sit down to watch The Last Survivors, be sure to have a bottle of water at the ready, and a jar of canned peaches, too. You will be craving both.
Link:
Last Survivors on Facebook
- Author: Kathy Keatley Garvey
He went from researching pest insects to targeting chronic pain in humankind.
He went from discovering a compound that alleviates pain (tested successfully on rodents, cats, dogs and horses) to forming a company EicOsis (pronounced eye-co-sis) to alleviate neuropathic and inflammatory pain in humans and companion animals.
Meet Bruce Hammock, the founder and CEO of EicOsis.
Hammock is a distinguished professor of entomology in the UC Davis Department of Entomology and Nematology who holds a joint appointment with the UC Davis Comprehensive Cancer Center.
He is on a mission, and clinical trials are on the horizon.
EicOsis has just received a $4 million federal grant to advance Hammock's compound discovery through Phase 1 clinical trials. The grant, “Development of an Oral Analgesic for Neuropathic Pain," is funded by the Blueprint for Neuroscience Research. National Institutes of Health (NIH).
The clinical trials, scheduled to begin in 2017, will target diabetic neuropathic pain, occurring in an estimated half of the world's 347 million diabetics, and 29 million Americans.
What exactly is the compound? It's "an inhibitor of the soluble epoxide hydrolase (sEH) enzyme,” said Hammock, whose fundamental research on the developmental biology of insects led to the discovery. “It is a key regulatory enzyme involved in the metabolism of fatty acids and treats pain by stabilizing natural analgesic and anti-inflammatory mediators.”
Many pain relievers are addictive, but not this one. Known as EC5026, the compound is “a potent, orally active and a non-narcotic analgesic that does not adversely affect the brain, gastrointestinal tract, or cardiovascular system,” said Alan Buckpitt, the company's vice president of pharmacology and emeritus professor of molecular biosciences at the UC Davis School of Veterinary Medicine.
“The EicOsis technology may solve a great need in pain treatment in providing a powerful analgesic which avoids the side effects of opioids (narcotics) and nonsteroidal anti-inflammatory drugs (NSAIDs),” said physician Scott Fishman, professor and chief of the Division of Pain Medicine, UC Davis Health System, who is not affiliated with the company. “The EicOsis compound holds great promise for controlling neuropathic pain in general and particularly for this difficult and common medical problem.”
A goal of the Blueprint Neurotherapeutics Network is to discover, develop and generate novel compounds that will ultimately be commercialized and benefit humankind.
When you think of all the havoc that diabetes wreaks (we all have family and friends suffering from the disease and its complications--and some 86 million Americans alone are pre-diabetic), it's good to see this exciting "bench-to-bedside" research.
"It's hard to know where science leads," Hammock acknowledged, noting that his research into how caterpillars turn into butterflies led to this treatment for pain.
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.
A member of the UC Davis faculty since 1980, 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.
Meanwhile, we're all anticipating the clinical trials and what EC5026 can do.
(Note: see main news story on the UC Davis Department of Entomology and Nematology website and links to his work.)
- Author: Kathy Keatley Garvey
From controlling insects to relieving human suffering...
Entomologist Bruce Hammock, distinguished professor of entomology at the University of California, Davis, who holds a joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center, is in the news.
Some forty years ago, he discovered an enzyme inhibitor that dramatically reduces inflammation, inflammatory pain and neuropathic pain.
Fast forward to July 6, 2015. In ground-breaking research estimated to affect millions of patients globally, the Hammock lab and the Fawaz Haj lab, Department of Nutrition, discovered a key mechanism that causes neuropathic pain--a complex, chronic and difficult-to-treat pain caused by nerve injuries from trauma or from such diseases as diabetes, shingles, multiple sclerosis and stroke.
A biological process, termed endoplasmic reticulum stress or ER stress, is the significant driver of neuropathic pain, said lead researchers Bora Inceoglu of the Hammock lab/UC Davis Comprehensive Cancer Center, and Ahmed Bettaieb of the Fawaz Haj lab.
The ground-breaking discovery has attracted worldwide attention since its publication July 6 in the Proceedings of the National Academy of Sciences.
“This is a fundamental discovery that opens new ways to control chronic pain,” said Hammock. "We can now specifically search for agents to control ER stress and its downstream pathways. This search is already underway in a number of laboratories working on cancer and other diseases.” (See news story.)
Who is Bruce Hammock? Holly Caster, editor of PAINWeek interviewed Hammock July 10 and published a Q&A today in a piece titled "Pain Reporter: The Professor and the Science Behind the Potential Management of Neuropathic Pain."
Hammock pointed out that his research "started as very fundamental research in developmental biology using insects as models. We found that the soluble epoxide hydrolase is highly conserved in evolution and asked its role in man and other mammals. We first found that inhibitors of the enzyme stabilize natural anti hypertensive compounds called EETs and reduced blood pressure. We then found that they reduced inflammation and inflammatory pain. We tried neuropathic pain as an indication because it is so difficult to treat and were surprised to find that the sEH inhibitor worked far better than drugs like gabapentin and Lyrica currently sold for neuropathic pain. I have attached a comparison. Having failed to interest large pharma companies in this biology we started a small company EicOsis to move the inhibitors to the clinic for treating pain in both companion animals and man. "
The research, Hammock noted, was initially done on rodents. "The fact that the compounds work in a variety of species builds confidence. It argues that with regard to neuropathic pain different species are similar (dog, horse, man, rat,etc.)" he told her. Read the full interview here: http://www.painweek.org/brainfood_post/pain-reporter-the-professor-and-the-science-behind-the-potential-management-of-neuropathic-pain/
Hammock acknowledged his long-term interest in nature and biology. "This was fostered by a wonderful boy scoutmaster who thought kids should be wandering in the woods and a great biology teacher who provided a microscope to me in high school and said 'go discover.' The move to entomology was further stimulated when I realized that the big cause of human suffering in the world was starvation caused in part by insects eating crops. It was also stimulated by realizing that insect-borne diseases dwarf cancer, heart disease, etc., in terms of human suffering. It is hard to know where science leads. In this case, asking how caterpillars turn into butterflies led to a treatment for pain."
Who would have ever thought that the study of caterpillars would lead to a treatment for pain?