- 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
Ecologist and research scientist Maria Silvina Fenoglio of Argentina will present a virtual seminar, hosted by the UC Davis Department of Entomology and Nematology, on "Do Green Roofs Benefit Urban Arthropod Communities? Evidence from a South American City," at 4:10 p.m., Wednesday, Oct. 6.
"Green roofs, beyond offering numerous environmental benefits, could mitigate the negative effects of urbanization on arthropods. However, the characteristics of green roofs that could favor arthropod biodiversity and ecological functioning are poorly known, especially for South American countries," Fenoglio says in her abstract. "In this talk, I will present the main results of our investigations in relation to these aspects."
UC Davis urban landscape entomologist Emily Meineke of the UC Davis Department of Entomology and Nematology is hosting the presentation. "Dr. Fenoglio's work is foundational to our current understanding of how insects respond to urbanization," Meineke said. "While the hypotheses she tests are diverse, they focus around how various aspects of land management shape beneficial insect communities, a topic that is critical for conservation today. I could not be more excited that she agreed to present her work to the department."
Since 2018 the ecologist has served as a National Geographic explorer. She works on projects related to urban ecology and the ecology of insect communities. "I have a particular interest in the study of urban green spaces (ie. green roofs, urban gardens) as refuges for biodiversity and as providers of ecosystem services mediated by insects," she says.
"My ultimate goal of my work is to find evidence that contributes to the development of more sustainable cities and helps to some extent to reconcile the lives of city dwellers with nature." When she's not in the lab or in the field, she enjoys yoga, painting, and spending time with her family, Camilo and Martín.
Her most recent publications include Arthropod Diversity and Ecological Processes on Green Roofs in a Semi-Rural Area of Argentina: Similarity to Neighbor Ground Habitats and Landscape Effects, published in July 2020 in the journal Landscape and urban Planning.
Coordinating the department's seminars is nematologist and assistant professor Shahid Siddique, who may be reached at ssiddique@ucdavis.edu.
Resources:
- Author: Kathy Keatley Garvey
The Bohart Museum of Entomology at the University of California, Davis, is helping to spread the biodiversity of insects.
Lynn Kimsey, director of the Bohart Museum and a distinguished professor of entomology, UC Davis Department of Entomology and Nematology, recently received a request for duplicate specimens of beetles, moths and butterflies for a Biodiversity Science Museum and Research Center to be headquartered at the research institution, Atatürk University, in Erzurum, Turkey.
“We're gifting them 350 large-bodied beetles, moths and butterflies for their display,” Professor Kimsey said. “The specimens are all duplicates of material we collected in Papua New Guinea about a decade ago.”
Levent Gültekin, a professor at Atatürk University, recently emailed Kimsey that he and his colleagues are working to create "a Biodiversity Science Museum and Research Center belonging to Atatürk University. Our concept will be actually a natural history museum. This is rather a new topic here, and it will be the first museum in Eastern Turkey if we can succeed. As a first step, we are working on a permanent exhibition in four settings: Arthropoda (majority insect) diversity, Plant diversity, Vertebrate and Paleodiversity.”
“For insect (and other arthropods), we are planning to hang 100 exhibition boxes (30x40 cm in size) to show great diversity for this group,” Professor Gültekin related, adding that “Our insect collection almost 100 percent comes from Turkey; but we would like to allocate one fourth of boxes for other zoogeographical realms except for Palearctic.”
The Bohart Museum is glad to oblige, Kimsey said.
Atatürk University is a land-grant university established in 1957 in Erzurum, located in the Eastern Anatolia Region. The university consists of 23 faculties, 18 colleges, 8 institutes and 30 research centers.W ikipedia says Atatürk "serves as "a hub of educational and cultural excellence for the Eastern Region." Some 6 million people populate the region.
The Bohart Museum, now celebrating the 75th anniversary of its founding (by UC Davis entomology professor Richard M. Bohart (1913-2007), is home to nearly 8 million insect specimens, collected from around the world. It also houses an insect-themed gift shop, now online; and a live “petting zoo,” comprised of Madagascar hissing cockroaches, stick insects and tarantulas.
Located in Room 1124 of the Academic Surge Building on Crocker Lane, the Bohart Museum is currently closed to the public due to the COVID-19 pandemic.
- Author: Kathy Keatley Garvey
Well, now you can.
A UC Davis professor will pay you--if you're a top-notch UC Davis student--to write (the equivalent of) a "term paper."
UC Davis distinguished professor James R. Carey of the Department of Entomology and Nematology will pay selected students $1000 each to write a paper dealing with human hibernation and longevity--a two-fold project aimed at assisting him with his research and helping students learn how to research, write, illustrate, finalize and deliver the equivalent of a quality term paper.
"With a heavy fall quarter teaching load and other demands during this academic year, I am in need of help in researching the literature on the biology of hibernation and concepts associated with its integration into the human life course," Carey announced, adding that he is "in the early stages of writing a theoretical paper tentatively titled “Human Hibernation as a Future Life Course Option."
The deadline to apply is 5 p.m., Friday, Oct. 1. UC Davis students at all levels and all majors may apply. "It's a report equivalent to the quality term paper I expect in my class that would receive an A or an A+," Carey said.
Carey said he hopes to assemble an interdisciplinary team of 10 to 12 students able and willing to invest the time (60-70 hours) to write the equivalent of a 2,500-word term paper on one of 10--or possibly more--topics. Research and writing efforts will be spread over the 2021-22 academic year. He will compile and format their papers in “proceedings” and publish as both a print and digital book, using the Barnes and Noble Press self-publishing website. The students are also free to re-purpose their papers.
Carey is seeking papers similar to the quality of the three award-winning term papers that his Longevity and Human Development students submitted in the UC Davis Lang Writing Prize Competition. Two students won the top prize in their categories in both 2020 and 2021, and another scored third place in 2021.
Paper Topics (Tentative)
1. Ecology and population biology of dormancy
2. Physiology and ecology of mammalian hibernation
3. Human torpor: Historical, accidental and medical
4. Prospective role of human hibernation in deep space exploration
5. Historical rates of biomedical progress in disease mitigation and cures
6. Reconfiguring the human life course
7. The biology, psychology and behavior of long-term isolation and separation
8. Personal, family and societal consequences of “dropping out”
9. The biology, behavior and psychology of individuals re-entering society
10. The future of human longevity: Emerging concepts
Students interested in participating in the project can email Carey at jrcarey@ucdavis.edu with the subject line “Human Hibernation Project" and include in the body:
- your UC Davis major and year
- your first and second choices of paper topic by number or topic (e.g., dormancy; life course; etc);
- whether you would be interested in participating if another student was assigned your topic(s) of greatest interest (yes/no)
- a 100 to 150-word statement on why you are interested and would be a good choice to join the team; and
- a 1-page (only) CV. Writing experiences and skills are a plus, he said, but "I am mostly interested in highly motivated and self-directed students who are willing to dive deeply into the literature related to my broad topic and to synthesize the results. I will teach you how to write your paper competently and professionally."
Carey will interview the top candidates via Zoom and make final selections within a week. If selected, they will have
"plenty of time" to enroll in his one-credit ENT 99 or 199, he said.
Timetable
Fall Quarter (2021): Frame, research and finish a preliminary working draft including at least rough figures and tables and references (using Endnotes bibliographic software).
Winter Quarter (2022): Complete research, finalize structure and submit near-final draft, all figures, tables and references cited finished
Spring Quarter (2022): Finalize narrative, figures, tables and references. Submit final version.
Carey, a senior scholar at the Center for the Economics and Demography of Aging at UC Berkeley, focuses his research on the biology and demography of aging and lifespan, particularly the use of insect models. A national-award winning teacher, he offers worldwide workshops on best practices in information design and presentation strategies. His most recent book is Biodemography: An Introduction to Concepts and Methods (2020, Princeton University Press), co-authored by Deborah A. Roach, professor and chair of the Department of Biology, University of Virginia.
- Author: Kathy Keatley Garvey
Seen any monarchs lately?
No, not the British royal family: the monarch butterfly, Danaus plexippus.
Butterfly guru Art Shapiro, UC Davis distinguished professor of evolution and ecology who has monitored butterfly populations of dozens of species in the Central Valley since 1972, says it's a poor year for monarchs.
He saw one monarch on Sept. 26 in Davis, and one on Sept. 27 in West Sacramento, both Yolo County. "The coastward migration is apparently afoot...all 6 dozen of them..." he lamented.
Shapiro earlier described the monarch population as on life support. A look at this graphic on the inaturalist site helps tell the sad tale.
Maybe the U.S. Department of Fish and Wildlife will declare it an endangered species?
From its website: "On December 15, 2020, the U.S. Fish and Wildlife Service announced that listing the monarch as endangered or threatened under the Endangered Species Act is warranted, but precluded by higher priority listing actions. The decision is the result of an extensive status review of the monarch that compiled and assessed the monarch's current and future status. The monarch is now a candidate under the Endangered Species Act; we will review its status annually until a listing decision is made."
The first five paragraphs of their news release, issued Dec. 15, 2020: "After a thorough assessment of the monarch butterfly's status, the U.S. Fish and Wildlife Service (Service) has found that adding the monarch butterfly to the list of threatened and endangered species is warranted but precluded by work on higher-priority listing actions. With this decision, the monarch becomes a candidate for listing under the Endangered Species Act (ESA), and its status will be reviewed each year until it is no longer a candidate."
“We conducted an intensive, thorough review using a rigorous, transparent science-based process and found that the monarch meets listing criteria under the Endangered Species Act. However, before we can propose listing, we must focus resources on our higher-priority listing actions,” said U.S. Fish and Wildlife Service Director Aurelia Skipwith. “While this work goes on, we are committed to our ongoing efforts with partners to conserve the monarch and its habitat at the local, regional and national levels. Our conservation goal is to improve monarch populations, and we encourage everyone to join the effort.”
“The Monarch Joint Venture is committed to continuing its conservation efforts for monarchs. Each of our partners, and many other stakeholders, come to the monarch conservation table with different approaches, audiences, strengths and opportunities to make a difference. There is a role for everyone in monarch conservation,” stated Wendy Caldwell, Executive Director, Monarch Joint Venture.
"Over the past 20 years, scientists have noted declines in North American monarchs overwintering in Mexico and California, where these butterflies cluster. Numbers in the larger eastern population are measured by the size of the area they occupy. At a density of roughly 8.5 million monarchs per acre, it is estimated that the eastern population fell from about 384 million in 1996 to a low of 14 million in 2013. The population in 2019 was about 60 million. The western population, located in California, saw a more precipitous decline, from about 1.2 million in 1997 to fewer than 30,000 in 2019."
"In 2014, the Service received a petition to list the species and published a substantial 90-day finding in December 2014. In 2016, the agency began an in-depth status assessment, looking at the global population as well as focusing on monarchs in North America, where 90% of the world's population occurs."
Meanwhile, the tally of sightings in the Yolo-Solano area is troubling. Beyond troubling....