- Author: Kathy Keatley Garvey
Dr. Panigrahy is an assistant professor of pathology, Beth Israel Deaconess Medical Center, Harvard Medical School.
His topic is "Pro-Resolution Lipid Mediators in the Resolution of Cancer," said Hammock, who holds a joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center.
The abstract: "For decades, cancer therapy has focused on killing cancer cells, from broad cytotoxic therapy to the inhibition of specific molecular pathways. However, cytotoxic cancer therapy may inherently be a double-edged sword as apoptotic tumor cells ('debris') may stimulate inflammation and tumor growth via a pro-inflammatory ‘cytokine storm'. Environmental carcinogens (e.g. Aflatoxin B1) can also generate debris which may stimulate inflammation and tumor dormancy escape. This is clinically relevant as 30-90% of humans harbor dormant tumors."
"To stimulate the natural debris-clearing process which would eliminate this source of tumor stimulation, we utilized endogenous specialized pro-resolving mediators (SPMs), specifically maresins, which are biosynthesized by human macrophages from endogenous docosahexaenoic acid. Additionally, novel COX-2/sEH inhibitors (e.g. PTUPB) can stimulate inflammation resolution more potently than either COX-2 or sEH inhibition alone by stabilizing epoxy-eicosanoids, promoting the formation of pro-resolving mediators such as lipoxins, and activating anti- inflammatory cytokine programs. In dramatic contrast to conventional anti-inflammatories, pro-resolving lipid mediators clear debris and counter-regulate a series of pro-inflammatory cytokines. We demonstrate that the resolution of inflammation represents a novel modality in cancer treatment by enhancing endogenous clearance of tumor cell debris and counter- regulating pro-tumorigenic cytokines."
Earlier this year, a collaborative research paper authored by Hammock, Panigrahy and colleagues won the Editor's Pick of the Journal of Investigation for the month of July. The paper, “Preoperative Stimulation of Resolution and Inflammation Blockade Eradicates Micrometastases,” relates how blocking inflammation and/or activating the resolution of inflamation before surgery can eradicate small tumors and promote long-term survival in experimental cancer modes. (See news story.)
Dipak was accepted into medical school at Boston University at age 17. He trained in surgery with Dr. Roger Jenkins, who performed the first liver transplant in New England. Over the past decade, Dr. Panigrahy led angiogenesis and cancer animal modeling in the Judah Folkman laboratory. He joined the Beth Israel Deaconess Medical Center in 2013, and in 2014 was appointed assistant professor of pathology and currently has a laboratory in the Center for Vascular Biology Research.
For more information on the seminar, contact Hammock Lab account manager Gregory Zebouni at gzebouni@ucdavis.edu or (530) 752-8465.
- Author: Kathy Keatley Garvey
Leal, a distinguished professor in the Department of Molecular and Cellular Biology and a former chair of the Department of Entomology (now the Department of Entomology and Nematology) is one of 168 distinguished academic inventors who will be inducted April 10 at NAI's ninth annual meeting in Phoenix. The only other UC Davis recipient: Cristina Davis, the Warren and Leta Geidt Endowed Professor and Chair, Department of Mechanical and Aerospace Engineering
“I am humbled by this honor,” said Leal, who was nominated by UC Davis chancellor emerita Linda Katehi, an NIA fellow inducted in 2012. “To express my sentiment I have to paraphrase my predecessor as president of the International Society of Chemical Ecology, late Professor Thomas Hartmann, who said in our meeting in Prague in 1996: ‘In academia, students, postdocs, and other associates do most of the work and professors received the honors.' I look forward to opportunities to support NAI's mission of promoting innovation and celebrating invention.”
Katehi, now of Texas A&M, where she is a distinguished TEES (Engineering Experiment Station) chair and professor, Department of Electrical and Computer Engineering, praised Leal's “novel, sustainable and continued contributions to the field of entomology and for their greater implications in molecular and cellular biology and the understanding of disease and prevention.” Leal holds 28 Japanese and two U.S. patents.
Leal is the second faculty member affiliated with the Department of Entomology to be selected an NIA fellow. Distinguished professor Bruce Hammock, who holds a joint appointment with the Department of Entomology and the UC Davis Comprehensive Cancer Center, received the honor in 2014. (See news story.)
Said Hammock: “When Walter Leal reached UC Davis, he came with the reputation of being a 'one man army in research.' This reputation was well deserved. I know of no one at UC Davis who matches Walter in taking his remarkable fundamental advances in science and translating them to increase the safety and magnitude of world food production.”
Insect Communication
Leal, an expert in insect communication investigates how insects detect odors, connect and communicate within their species; and detect host and non-host plant matter. His research, spanning three decades, targets insects that carry mosquito-borne diseases as well as agricultural pests that damage and destroy crops. He and his lab drew international attention with their discovery of the mode of action of DEET, the gold standard of insect repellents. (See the Leal lab's work on DEET in Entomology Today.)
He and his collaborators, including Nobel Laureate Dr. Kurth Wuthrich (Chemistry 2002), unravel how pheromones are carried by pheromone-binding proteins, precisely delivered to odorant receptors, and finally activated by pheromone-degrading enzymes.
That led to Leal's identification of the sex pheromones of the navel orangeworm (Amyelois transitella), a pest of almonds, figs, pomegranates and walnuts, the major hosts. This has led to practical applications of pest management techniques in the fields.
Leal, a fellow of the Entomological Society of America (ESA), "has greatly advanced scientific understanding of insect olfaction," said Joe Rominiecki, communications manager, Entomological Society of America. "He has identified and synthesized several insect pheromones, and his collaborative efforts led to the first structure of an insect pheromone-binding protein."
'Tangible Impact on Quality of Life'
“The NAI Fellows Program highlights academic inventors who have demonstrated a spirit of innovation in creating or facilitating outstanding inventions that have made a tangible impact on quality of life, economic development and the welfare of society,” said NIA director Jayde Stewart. “Election to NAI Fellow is the highest professional distinction accorded solely to academic inventors. To date, NAI Fellows hold more than 41,500 issued U.S. patents, which have generated over 11,000 licensed technologies and companies, and created more than 36 million jobs. In addition, over $1.6 trillion in revenue has been generated based on NAI Fellow discoveries.”
A native of Brazil, educated in Brazil and Japan, and fluent in Portuguese, Japanese and English, Leal received his master's degree and doctorate in Japan: his master's degree at Mie University in 1987, and his doctorate in applied biochemistry at Tsukuba University in 1990. Leal then conducted research for 10 years at Japan's National Institute of Sericultural and Entomological Science and the Japan Science and Technology Agency before joining the faculty of the UC Davis Department of Entomology in 2000. He served as chair of the department from July 2006 to February 2008.
Leal co-chaired the 2016 International Congress of Entomology meeting, "Entomology Without Borders," in Orlando, Fla., that drew the largest delegation of scientists and experts in the history of the discipline: 6682 attendees from 102 countries.
Leal served as president of the International Society of Chemical Ecology and ESA's Integrative Physiological and Molecular Insect System Section. He co-founded the Asia Pacific Association of Chemical Ecologists and played a key role in founding the Latin American Association of Chemical Ecology.
Among his many other honors, Leal is a fellow of the American Association for the Advancement of Science and the California Academy of Sciences; an honorary fellow of the Royal Entomological Society and an inductee of the Brazilian Academy of Sciences. He received a silver medal from the International Society of Chemical Ecology. Leal recently presented the Founders' Memorial Lecture at the ESA meeting in St. Louis, the first UC Davis scientist selected to do so.
“Walter is an amazing person and an amazing scientist,” said Fred Gould, distinguished professor in the Department of Entomology and Plant Pathology at North Carolina State University. “His work has opened new doors to the understanding of how insects receive and perceive odors and has saved farmers in California and Brazil more than $100 million. He's at a point where he could sit back and bask in the glory of his accomplishments, but that is not Walter. He remains as prolific as ever.”
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- Author: Kathy Keatley Garvey
EicOsis LLC, a company founded by UC Davis distinguished professor Bruce Hammock to develop a non-opiate drug to relieve inflammatory pain in companion animals and target chronic neuropathic pain in humans and horses, can now add “Sacramento Region Innovator of the Year” to its list of accomplishments.
EicOsis won the award in the medical health/biopharmaceutical category of the annual Sacramento Region Innovation Awards Program. The program “recognizes the area's vibrant innovation community—from emerging to established companies—and their breakthrough creations,” according to sponsors Stoel Rives LLP, Moss Adams LLP and the Sacramento Business Journal.
“This project is an illustration of how fundamental science leads to real world applications, in this case addressing severe pain of humans and companion animals,” said Hammock, chief executive officer of EicOsis and a UC Davis faculty member who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. “Our success in translation has been due largely to support from a number of institutes of the National Institutes of Health and a small team of hard-working scientists.”
The ceremony, honoring the winners of the eight categories, took place Nov. 7 in the Crest Theatre, Sacramento. Judges scored the finalists on novelty, market need, economic or social impact and disruption.
“It was an honor to be awarded the Sacramento Region Innovator of the Year in Medical Health and BioPharma,” said Cindy McReynolds, senior program manager of EicOsis and a UC Davis doctoral candidate studying pharmacology and toxicology. “The companies represented were inspiring, and it is great to be a part of the innovation going on in the Sacramento region.”
“Chronic pain is an enormous emotional and economic burden for more than 100 million people in the United States alone,” said Hammock, who co-founded EicOsis in December 2011 to alleviate pain in humans and companion animals. “The extreme and poorly treated pain that I observed as a medical officer working in a burn clinic in the Army, is a major driver for me to translate my research to help patients with severe pain.”
Phase 1 human clinical trials to test the drug candidate, EC5026, a first-in-class, small molecule that potently inhibitssEH, will begin Dec. 10 in Texas. The title: "A Single-Center, Double-Blind, Placebo-Controlled, Phase 1a Single Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Sequential Dose Regiments of Oral EC5026 in Healthy Male and Female Subjects." Eight will participate; six with the drug candidate and two with the placebo. The technology was discovered in the Hammock lab and UC Davis has licensed patents exclusively to EicOsis.
“EC5026 is a key regulatory enzyme involved in the metabolism of membrane fatty acids,” Hammock said. "It's a novel, non-opioid and oral therapy for neuropathic and inflammatory pain. Inhibition of sEH treats pain by stabilizing natural analgesic and anti-inflammatory mediators."
The project is unique in that “there have been very few truly new types of analgesic compounds that have reached the market in the past 50 years,” Hammock said.
“The sEH enzyme is involved in regulating the activity of powerful anti-inflammatory fatty acids called EETs that are present in all cells in humans and animals,” the scientists explained in their awards application. “EETs are anti-inflammatory, analgesic, anti-hypertensive, but they are short lived molecules that are normally eliminated within seconds. By inhibiting sEH, EET levels can be increased by 4x or more and maintained at high anti-inflammatory and analgesic levels for 24 hours or longer.”
“The sEH inhibitors are very potent molecules that are designed for once daily oral dosing. They can also be administered intravenously for acute pain (e.g. equine laminitis),” they wrote. “Preclinical safety studies show that sEH inhibitors are very safe with no visible signs of toxicity at doses more than 100x higher than the therapeutic dose levels. Unlike conventional analgesics, they do not produce sedation or cognitive dysfunction and they have been shown to have no addiction liability, no adverse cardiovascular effects, and no adverse effects on the gastrointestinal tract. They can be safely co-administered with existing analgesic medications.”
Approximately 50 million Americans (20 percent of the population) suffer from chronic pain, according to the Center for Disease Control and Prevention. The annual economic toll is $560 billion, encompassing direct medical expenses, lost productivity, and disability claims. Pain research is now one of the top priorities of the National Institutes of Health (NIH).
EicOsis advancement of EC5026 into clinical trials has been funded as part of the Blueprint Neurotherapeutics Network (BPN) of the NIH Blueprint for Neuroscience Research. The BPN is a collaboration of NIH Institutes and Centers that supports innovative research on the nervous system with the goal of developing new neurotherapeutic drugs.
EicOsis (pronounced eye-cosis), derives its name from eicosanoid, “the major backbone of chemical mediators in the arachidonate cascade,” said McReynolds. “It symbolizes the epoxide group in chemistry, which is key to the anti-inflammatory chemical mediators and where the biochemical target called soluble epoxide hydrolase works.”
- Author: Kathy Keatley Garvey
A Davis-based company founded by UC Davis distinguished professor Bruce Hammock has received the green light to begin Phase 1 clinical trials to test a non-narcotic drug candidate developed in the Hammock lab to alleviate chronic pain.
EicOsis LLC, a pharmaceutical startup, has received Investigational New Drug (IND) approval from the U.S. Food and Drug Administration to test the drug candidate, EC5026. Clinical trials are expected to begin this year.
"EicOsis is developing a new class of oral non-narcotic analgesics based on inhibition of the soluble epoxide hydrolase (sEH) enzyme," said EicOsis chief executive officer Hammock, who holds a joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. UC Davis has licensed EC5026 exclusively to EicOsis.
EC5026 (BPN-19186) is described as a first-in-class, small molecule that potently inhibits soluble epoxide hydrolase (sEH). "It is key regulatory enzyme involved in the metabolism of membrane fatty acids," Hammock said. "Inhibition of sEH treats pain by stabilizing natural analgesic and anti-inflammatory mediators."
The sEH inhibitors developed by EicOsis have already shown to be effective for inflammatory and neuropathic pain in the rodents, horses, dogs and cats, with no apparent adverse or addictive reactions.
“Chronic pain management is a serious public health crisis with few options available that provide effective relief free of life-threatening safety concerns including abuse,” said UC Davis physician Scott Fishman, the Fullerton Endowed Chair in the Department of Anesthesiology and Pain Medicine, and professor and director of the Center for Advancing Pain Relief at the UC Davis School of Medicine. “The medical community is continually seeking effective pain management strategies. EicOsis's new compound is a novel pharmacological approach for treating pain, and I remain optimistic for its success.”
Approximately 50 million Americans (20 percent of the population) suffer from chronic pain, according to the Center for Disease Control and Prevention (CDC). The annual economic toll is $560 billion, encompassing direct medical expenses, lost productivity, and disability claims. Pain research is now one of the top priorities of the National Institutes of Health (NIH).
EicOsis advancement of EC5026 into clinical trials has been funded as part of the Blueprint Neurotherapeutics Network (BPN) of the NIH Blueprint for Neuroscience Research. The BPN is a collaboration of NIH Institutes and Centers that supports innovative research on the nervous system with the goal of developing new neurotherapeutic drugs.
“There is clear unmet need for new pain therapeutics," said BPN Program Director Charles L. Cywin. "sEH is an important pain target in our portfolio and we are excited to see EC5026 advance to human clinical development on the pathway to treating patients."
The development of EC5026 also drew financial support from the Helping to End Addiction Long-term, or the NIH HEAL Initiative via a grant to EicOsis, which is using the funds to de-risk the development process of EC5026 and to accelerate the start of clinical trials.
"It's clear that a multi-pronged scientific approach is needed to reduce the risks of opioids, accelerate development of effective non-opioid therapies for pain and provide more flexible and effective options for treating addiction to opioids,” said NIH Director Francis S. Collins, who launched the initiative in early 2018. “This unprecedented investment in the NIH HEAL Initiative demonstrates the commitment to reversing this devastating crisis.”
Contacts:
Media inquiries: info@eicosis.com
Investor inquiries: Cindy McReynolds at cbmcreynolds@eicosis.com
- Author: Kathy Keatley Garvey
Thomas Sparks, the first graduate student of UC Davis distinguished professor Bruce Hammock, is the 2019 recipient, following in the generational footsteps of Hammock, his major professor at UC Riverside and UC Davis; and Hammock's major professor, the late John Casida of UC Berkeley.
Sparks accepted the award at the recent ACS meeting in San Diego. Hammock received the Spencer award in 1993, and Casida in 1978.
In his talk, Sparks acknowledged that he was a “third generation winner” following Casida and Hammock. "I was surprised to get a very large response / applause for this--very gratifying and likely testimony to the high regard for John Casida and Bruce Hammock."
"I was there cheering for Tom," Hammock said. "He gave a wonderful talk. Actually, I was there with Tom and our wives and my second student Keith Wing."
Casida, Hammock, Sparks and Wing also won the ACS International Award for their research: Casida, the inaugural winner, won it in 1969; Hammock in 1992; Sparks in 2012, and Wing in 2015.
Sparks, a native of San Francisco who grew up in a farming community in the central valley, is an internationally recognized leader in the discovery of new insect control agents, the biochemistry and toxicology of insecticides, and insecticide resistance. Formerly a professor at Louisiana State University (LSU) and then a researcher in private industry for three decades, he recently retired as a research fellow from Corteva Agriscience (formerly Dow AgroSciences).
“Tom was instrumental in the discovery and development of a new class of insecticides called spinosids,” said Hammock, who holds a joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. Spinosad, launched in 1997, is a naturally occurring mixture of spinosyns. Sparks co-invented the next-generation semi-synthetic spinosyn-based insecticide, spinetoram, that improved the efficacy, spectrum, and residual of spinosad. Both compounds received the EPA Presidential Green Chemistry Challenge Award, spinosad;in 1999 and spinetoram in 2008.
Sparks praised the broad training and inspiration he received in Hammock's lab as “outstanding preparation for my future roles in science.”
Sparks served on LSU's Department of Entomology faculty from 1978 to 1989 as an insect toxicologist, achieving full professor. His research covered endocrine regulation of insect metamorphosis, insecticide resistance, and insecticide biochemistry and toxicology.
In 1989, Sparks joined the agrochemical research group, the joint venture between Eli Lilly and The Dow Chemical Company, DowElanco (later known as Dow AgroSciences). He worked in discovery research for nearly three decades.
Sparks holds 46 patents or patent applications and continues to publish widely. He has published more than 175 refereed journal publications, book chapters, and other articles. Many involve a variety of discovery efforts in innovative insecticidal chemistries.
In recognition of this work, Thomas was named R&D Magazine's 2009 Scientist of the Year, the first in the 50-year history of the award for a scientist working in the field of agriculture. He also received the ACS International Award for Research in Agrochemicals (2012) and the AGRO Award for Innovation in Chemistry of Agriculture (2015). He is a Fellow of the Entomological Society of America and, in 2018, received the Entomological Society of America Recognition Award in Insect Physiology, Biochemistry and Toxicology.
Other UC Davis-affiliated recipients of the Spencer Award include the late Emil Mrak, for whom Mrak Hall is named.
The award memorializes Kenneth A. Spencer (1902-1960), a Kansas City geologist, engineer, coal miner, philanthropist and owner of the Spencer Chemical Company.
(ACS contributed to this article.)
