- Author: Kathy Keatley Garvey
Leal, a leading global scientist and inventor in the field of insect olfaction and communication and known for his impact in the fields of molecular, cellular biology and enotmology, received his medal at a June ceremony in Phoenix.
NIA selected him an NAI Fellow in 2019. However, the COVID pandemic cancelled the 2019 ceremony in Phoenix. Then in 2020, travel restrictions interfered with his plans to attend the Tampa, Fla., ceremony. Elected Fellows are required to attend the induction ceremony within two years of election in order to receive their award.
Leal attended the ceremony with his wife, Beatriz; daughter Helena; and son Gabriel. Both have co-authored papers in the Leal lab, "so they represent all visiting scholars, collaborators, postdocs, project scientists, graduate students, and undergraduate students in my lab," he commented. (See video of the awarding of the medals)
NAI singles out outstanding inventors for their “highly prolific spirit of innovation in creating or facilitating outstanding inventions that have made a tangible impact on the quality of life, economic development, and welfare of society.” Election to NAI Fellow is the highest professional distinction accorded solely to academic inventors. The NAI Fellow program has 1,403 Fellows worldwide representing more than 250 prestigious universities and governmental and non-profit research institutes.
Leal is the second faculty member affiliated with the Department of Entomology and Nematology to be selected an NAI fellow. Distinguished professor Bruce Hammock, who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center, received the honor in 2014.
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.
He and his collaborators, including Nobel Laureate 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.
At the time of his election to NAI Fellow, Joe Rominiecki, communications manager of Entomological Society of America (ESA), said Leal has “greatly advanced scientific understanding of insect olfaction. He has identified and synthesized several insect pheromones, and his collaborative efforts led to the first structure of an insect pheromone-binding protein."
ICE Council. Leal was recently elected chair of the International Congress of Entomology Council, which selects a country to host the congress every four years and which supports the continuity of the international congresses of entomology. Leal succeeds prominent entomologist May Berenbaum of the University of Illinois, Urbana-Champaign, editor-in-chief of the journal, Proceedings of the National Academy of Sciences and a 2014 recipient of the National Medal of Science.
“I have big shoes to fill,” he said.
Leal's name is currently on the ESA ballot to become an Honorary Member, the highest ESA honor. The Royal Entomological Society named him an Honorary Fellow in 2015.
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 chaired 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.
Among his many other honors, Leal is a Fellow of ESA, the American Association for the Advancement of Sciences and the California Academy of Sciences. He is a past president of the International Society of Chemical Ecology and corresponding member of the Brazilian Academy of Sciences. In 2019, ESA selected him to present its annual Founders' Memorial Lecture, the first UC Davis scientist selected to do so.
This year Leal received the UC Davis Academic Senate's Distinguished Scholarly Public Service Award for his series of four global webinars educating the public about COVID-19. The online symposiums drew more than 6000 viewers from 35 countries. Hammock, who nominated Leal for the award, praised his “extraordinary spirit of public service and selflessness in creating, organizing, and moderating a series of four COVID-19 symposiums at the beginning of the COVID-19 pandemic. He spearheaded public awareness, helped educate the public, eased concerns, and translated the scientific data into lay language. His symposiums drew global attention and brought prestige to UC Davis. It was a crucial time in our history.”
In addition to research and public service, teaching is another of Leal's passions. The UC Davis Academic Senate selected him for its 2020 Distinguished Teaching Award for Undergraduate Teaching, and the College of Biological Sciences singled him out for its 2022 Faculty Teaching Award.
"I don't teach because I have to," Leal recently said. "I teach because it is a joy to light the way and to spark the fire of knowledge."
- Author: Kathy Keatley Garvey
Hammock, who now holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center, knows too well what fire can do to victims.
So do other members of the Hammock lab and the Department of Surgery, University of Cincinnati College of Medicine (UC CoM).
They've just published research in the Proceedings of the Natural Academy of Sciences detailing their discovery of a key regulatory mechanism in inflammation that may lead to resolving inflammation in burn patients, as well as sepsis, cancer and COVID patients.
Basically, they discovered a pathway that regulates the immune response after infection or injury, such as burns. Dysregulation of this pathway could differentiate those who are at risk of fatal sepsis or help identify targets to resolve this unregulated inflammation.
“We are very excited about the findings in this paper and the far-reaching impacts it could have on understanding a key regulatory step in the immune response,” said co-lead author and researcher Cindy McReynolds of the Hammock lab and director of research at EicOsis, a Davis-based company founded by Hammock. Hammock, the corresponding author of the publication, has been involved in enzyme research for more than 50 years.
“This dysregulation has fatal consequences in serious diseases such as COVID, cancer, sepsis, burn, where fatality rates can be as high as 40 percent in severe cases,” she said. “An understanding of these pathways can help identify patients at risk of developing serious disease or identify new therapeutic targets for treatment.”
The research, titled "sEH-Derived Metabolites of Linoleic Acid Drive Pathologic Inflammation while Impairing Key Innate Immune Cell Function in Burn Injury,” is co-authored by Debin Wan, formerly of the Hammock lab and now a scientist at Escape Bio, San Francisco; Nalin Singh of the Hammock lab; and three UC CoM researchers: Charles Caldwell, professor and director, Division of Research, Department of Surgery; Dorothy Supp, adjunct professor in the Department of Surgery and a scientific staff member at Shriners Children's Ohio; and Holly Goetzman, principal research assistant in the Caldwell lab.
It's a complicated research project, but a crucial one to help humanity.
And that's what EicOsis is all about, as well. Hammock founded EicOsis in December 2011 to advance novel, safe and effective oral treatments for patients suffering from pain and inflammation. The LLC is developing a new class of oral non-narcotic analgesics based on inhibition of the soluble epoxide hydrolase enzyme. Human clinical trials are underway to test the drug candidate, EC5026, a first-in-class, small molecule that potently inhibits sEH. The sEH inhibitors have already shown to be effective for inflammatory and neuropathic pain in animals, with no apparent adverse or addictive reactions.
- Author: Kathy Keatley Garvey
Make that 986 pages or a four-inch-thick document.
Everyone who visits the Briggs Hall office of UC Davis distinguished professor Bruce Hammock can't imagine that, either.
Hammock, who holds a joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Center, inherited an “Odell's Type Writer,” patented in 1889 by inventor Levi Judson Odell (1855 - 1919), and the prized possession of his grandfather, Judge William Thomas Hammock (1866-1950) of Little Rock, Ark.
“This model is one of our nation's oldest linear index typewriters,” Hammock says. "It has no keyboard. It has a rail-type system with the characters spread out in a straight line--and not in alphabetical order, either. This is confusing compared to the modern-day QWERTY keyboard design, yet this instrument saved my grandfather's career.”
Not only did it save Judge Hammock's career, but Judge Hammock and his “type writer” inspired the development of Professor Hammock's 42-year career at UC Davis, which includes founding director of the UC Davis Superfund Research Program (SRP), funded by the National Institute of Environmental Health Sciences (NIEHS). Since 1987, he Hammock-directed program has brought in more than $90 million in grants to the UC Davis campus.
And fortunately, the 986-page grant renewal that the Hammock team submitted to NIEHS last year didn't involve the “back-up typewriter.”
Has Hammock used it? Yes, but only once. "Yes, it worked, but I won't use it ever again. It is too old and fragile. And to use it, you need a strong arm to hit the keys, especially if you have multiple carbons. And you can't see what you're typing. A metal bar blocks your view.”
Hammock has a 1915 newspaper clipping from The Arkansas Gazette showing his grandfather and daughter Maude working in the attorney's office. The Odell was proclaimed to be the oldest such machine in the county--older than the one that newspaper rival The Arkansas Democrat touted.
“The oral history of the typewriter is that William Thomas Hammock was living in the country town of Quitman, Ark., in 1893 and had just passed the bar," the UC Davis professor related. "Being a new attorney with no business and lots of spare time, he jumped at a $150 contract to make a copy of the county's handwritten laws and regulations. Not being an experienced lawyer, he failed to read the fine print. The county wanted not one, but 10 handwritten copies. This was impossible on his budget.”
“Then he heard about something called a ‘type writer.' He boarded a train to Chicago, where the Odell type writer company had just relocated from Wisconsin, checked out the machine, and bought it for about $15. This invention permitted him to use carbons and he only needed to type the documents twice, with multiple carbons.”
You had to be strong to operate the machine. "The number of carbon copies that can be made with the Odell is limited only by the strength of the operator's right arm," according to The Arkansas Gazette article. "Mr. Hammock took setting up exercises each morning and made 10 copies at a time. After a couple of months, he was as husky as a blacksmith and had earned $150. Mr. Hammock became quite proficient in handling the machine. He could pound out a line of legal phraseology much quicker than his forebears could chisel out a love message on stone or parchment, though the physical effort was about the same."
Hammock, widely known for his groundbreaking research in insect physiology, toxicology, pharmacology, and experimental therapeutics, joined the UC Davis faculty in 1980 from UC Riverside. He remembers typing grants on typewriters—pounding the keys, sliding the carriage return, and hearing the familiar ding. “For most work, I had an upright Remington at that time. The transition to computers started with magnetic card machines when I was at UC Riverside. When I joined the UC Davis faculty, I bought a PDP 1123 computer with Ted Wilson, a research scientist in the department, and we converted the text editor into a word processor and allowed people in the department to join our self-designed network for free. In some ways, it worked better than the current word processors.”
“Just as this new technology of the Odell type writer saved my granddad's career as a lawyer, this adapted word processor on the rather ‘Dr. Who-ish' PDP computer changed my career at UC Davis when we received that NIEHS grant in 1987 to establish the UC Davis Superfund Research Program. It's now the longest running Superfund Program in the country.”
The Hammock-directed program encompasses five projects and six cores, spread throughout most of the colleges, and involving more than 12 departments, eight labs and 35 personnel, as well as several dozen undergraduate and graduate students and collaborators. In addition to the grant funding, the SRP receives supplemental funding for multiple training, equity and outreach projects. The 2021-22 budget? A little over $2.6 million.
“We have addressed multiple problems in California ranging from the clean-up of the Mare Island Naval Shipyard through the MTBE (methyl tertiary-butyl ether) groundwater crisis to now helping the Yurok Nation in Northern California deal with environmental contamination,” Hammock said. “To compete for centers, program projects and training grants, we need not only good science but also the administrative infrastructure to put together proposals.”
Recalling his initial application for the federal grant, Hammock commented that “the opportunity for a large interdisciplinary grant with a very short time line arose from NIEHS. Applicants had to put together engineers, soil chemists, toxicologists, medical doctors and veterinarians in an integrated project on a short time line.”
“We never could have pulled this off without the technology of a word processor,” Hammock said, adding, “or without a wonderful department staff. Having the administrative staff, in this case Dee Dee Kitterman and the word processing technology of the PDP, made the difference. The renewal that went in this year was 986 pages! It makes you appreciate the collaborative nature of the science at Davis, the quality of the science, and particularly the administrative structure that supports it. We would not compete without the modern-day equivalents of the Odell Type Writer and the professionals who make our equipment sing.”
“Administrative staff are crucial,” Hammock said. “They should be appreciated all year around, not just on a single day (Administrative Professionals Day is April 27). And to think that in the past, our administrative professionals—then known as secretaries faced these challenges— with such formidable equipment as Odell's Type Writer—and won.”
- Author: Kathy Keatley Garvey
A drug candidate discovered and developed decades ago in the laboratory of UC Davis distinguished professor Bruce Hammock may help control the body's raging and often deadly inflammatory response to chemotherapy treatments, especially for pancreatic and liver cancer patients.
A 16-member international research team, based in the laboratories of Dipak Panigrahy of Harvard Medical School and Hammock, announced the findings in a newly published paper in the journal Proceedings of the National Academy of Sciences (PNAS).
Working in rodent models of liver and pancreatic cancer, they found that they could use a combination of two drugs to reduce inflammation following chemotherapy. Inflammation associated with debris from dying tumor cells can trigger metastasis, the spread of cancer throughout the body.
“We discovered that we can reduce or clear the chemotherapy-generated inflammation by inhibiting or blocking the enzyme, soluble epoxide hydrolase (sEH), and the EP4 prostaglandin receptor,” said co- senior author Hammock, who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. He is a member of the National Academy of Sciences.
“Basically, when we blocked both the sEH and EP4 eicosanoid pathways, the compounds worked together, preventing pancreas and liver cancer metastasis by stimulating the clearance of debris from prior cancer treatment,” said co-senior author Panigrahy, a physician-researcher with the Israel Deaconess Medical Center, Harvard School of Medicine.
“INV-1120 is a highly potent and selective EP4 antagonist currently in a Phase I clinical trial in the United States (Texas),” said co-senior author Yongkui Sun, chairman of Ionova Life Science, a biotechnology company in China that translates basic biomedical research discoveries into novel therapeutics for cancer. “It demonstrated monotherapy effect and strong synergy with anti-PD-1, the sEH candidate or gemcitabine in fighting cancers such as pancreatic and liver cancers in preclinical animal models.”
Lead author of the paper, “Eicosanoid Regulation of Debris-Stimulated Metastasis,” is Jianjun Deng, a Harvard Medical School researcher. “Chemotherapy results in excessive inflammation and a cytokine/lipid storm caused by the human body's reaction to this pancreatic cancer therapy,” he said. “The debris increases the sEH and EP4 proteins, which trigger a macrophage-derived storm of pro-inflammatory and pro-angiogenic lipid autacoid and cytokine mediators.”
“Controlling the body's inflammatory response to chemotherapy will likely be important to prevent metastasis,” Hammock said. “It hit me that what we really need to do is not so much block cytokines as to move upstream to modulate them and resolve them rather just block inflammation.”
“One way to modulate cytokines is to regulate the upstream eicosanoid pathways including sEH and EP4. The current discovery showed a very nice example by holistically modulate the eicosanoids to prevent pancreatic cancer and metastasis,” said co-lead author Jun Yang, a research scientist in the Hammock lab.
Sun said that “Among many of the insidious characteristics of cancer, cancer uses its dying cells to ‘train' the immune system to create a tumor microenvironment more favorable for its survival. Dying cancer cells can trigger inflammatory responses and release of cytokines, many of which are pro-tumor growth. Cancer uses this ‘positive feedback cycle' to combat cancer therapies, rendering them less effective.”
Other co-lead authors of the paper, are Haixia Yang, a researcher at China Agricultural University, Beijing China; and Victoria Haak, a first-year medical student at the University of Buffalo. At UC Davis, Hammock lab researchers also include Sung Hee Hwang, who made many of the compounds.
Hammock and Panigraphy described the research as a “novel but simple and effective approach.” Combining drugs to block the sEH and EP4 pathways is a novel approach to turning down the inflammation and preventing the cytokine storm caused by chemotherapy and even tumor resection, they said.
“We can increase the concentration of natural pro-resolving mediators termed EETs which act on a biological system to produce other pro-resolution mediators which modulate inflammation and actively resolve the process,” Hammock explained.
Hammock founded the UC Davis-based EicOsis Human Health LLC to bring the inhibitor to human clinical trials, now underway in Texas. “Since this soluble epoxide hydrolase inhibitor acts upstream to down-regulate the eicosanoid and the cytokine storm,” he said, “we are optimistic that it can help patients.”
“The techniques developed and used in this publication have tremendous potential to translate to the clinic,” said Panigrahy.
ACS estimates 42,230 new cases (29,890 in men and 12,340 in women) will be diagnosed this with primary liver cancer this year. About 30,230 people (20,300 men and 9,930 women) will die of these cancers. “Liver cancer incidences rates have more than tripled since 1980, while the death rates have more than doubled during this time,” according to an ACS cancer site.
The Hammock-Panigrahy labs not only have elucidated how chemotherapy increases cancer risk, but their collaborative work shows promise for preventing metastasis and recurrence of cancer following surgical tumor resection and chemotherapy. “These exciting studies show that pre-operative or peri-chemotherapeutic management of inflammation may stave off cancer recurrences,” Panigrahy said.
“It is always important to realize that the most significant translational science we do in the university is fundamental science,” said Hammock, marveling that “this all began by asking how caterpillars turn into butterflies.”
The research drew major funding from the National Institutes of Health (NIH) through two grants to Hammock, who directs the Superfund Program at UC Davis. He received grants from the National Institute of Environmental Health Sciences (NIEHS) Superfund Research Program; and the NIH RIVER (Revolutionizing Innovative, Visionary Environmental Health Research) Program. The research was also funded by three grants to Panigrahy: Credit Unions Kids at Heart; Joe Andruzzi Foundation; and the C.J. Buckley Pediatric Brain Tumor Fund.
Publication:
PNAS research article
- Author: Kathy Keatley Garvey
ESA announced the award today.
Sparks, who holds a doctorate in entomology (1978) from UC Riverside, was the first graduate student of then UCR faculty member Bruce Hammock, who joined the UC Davis faculty in 1980.
“This is a huge honor and directly due to Bruce's influence,” said Sparks, a retired research fellow at Corteva Agriscience (a Dow AgroSciences) in Indianapolis, Ind. He will receive the award at ESA's annual November meeting, to take place in Denver, Colo.
The award recognizes creative entomologists who have demonstrated the ability to find alternative solutions to problems that significantly impact entomology.
Sparks is the first scientist from the crop protection industry to receive the Nan-Yao Su Award and the second Hammock lab alumnus to do so. ESA selected Bryony Bonning, a former postdoctoral researcher in the Hammock lab and now a professor at Iowa State University, for the award in 2013. Walter Leal, former chair of the entomology department and now a UC Davis distinguished professor with the UC Davis Department of Molecular and Cellular Biology, won the award in 2011.
“As a graduate student studying insect physiology and toxicology, Tom was amazingly innovative,” said Hammock, who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. “He was in the lab early, he stayed late and he 'sang while he worked.” (Sparks says he sang "because no radios were allowed in the lab.")
“Fifty years later this is mainline biological chemistry,” Hammock pointed out, adding that Sparks started in biological control and then moved to insect physiology and toxicology (Hammock's lab) while in graduate school at UC Riverside. After graduate school, Sparks served as a professor of insecticide biochemistry and toxicology with the Louisiana State University's Department of Entomology. He then headed to Indianapolis to join Eli Lilly and Co., which shortly thereafter became DowElanco, then Dow AgroSciences, and finally Corteva Agriscience.
Sparks' lifelong focus is on developing green pesticides, Hammock said. “His greatest success of many successes has been with a complex group of what are known as polyketides. Specifically, Tom pioneered the spinosids as a new class of selective pesticides for integrated pest management (IPM). Tom was a leader in this program from the concept of natural product compounds through structural optimization to integration into pest management and resistance management programs nationally and internationally.”
“Dr. Sparks is internationally recognized as a leader and innovator in the field of insect biochemistry and toxicology, especially as it relates to the discovery of new crop protection compounds,” wrote Ronda Hamm of Corteva Agriscience, Indianapolis, who headed the nomination team.
A member of ESA for more than 40 years, Sparks “has a history of bringing new ideas and innovative approaches to the discovery of new insect control agents, resulting in several commercial products,” Hamm pointed out. “Through his innovative application of state-of-the art technologies, Dr. Sparks has succeeded in catalyzing the discovery and development of natural product-based compounds for the control of pest insects. One particularly relevant measure of Dr. Sparks' innovation is patents--unusually for a non-chemist, he has 47 patents covering a wide range of chemistries and ideas as it applies to the control of agricultural pests.”
Hammock praised Sparks for his innovative accomplishments. “For the past several decades, Dr. Sparks' goal has been to provide new, greener, tools that will allow growers and farmers around the world to feed an expanding global population," Hammock said. "To this end, Dr. Sparks employed an array of innovative approaches to the discovery of new insect control agents. His innovations are well-illustrated by his ‘what if..' questions and his answers and results from those questions.”
(Editor's Note: See list of other 2021 ESA winners)
