- Author: Kathy Keatley Garvey
Most studies of traumatic brain injuries (TBI) focus on the pathology of the injured brain, but newly published research indicates that the liver plays an important role in TBI, and a soluble epoxide hydrolase (sEH) inhibitor discovered by UC Davis distinguished professor Bruce Hammock could lead to therapeutic treatment.
The research, led by Professor Xinhong Zhu of the School of Biology and Biological Engineering, South China University of Technology, Guangzhou, and tested in the Zhu lab, appears in the Proceedings of the National Academy of Sciences (PNAS). Youngfeng Dai, PhD., is the first author.
“Using animal models, we found that the liver has a neuroprotective effect in the pathophysiology of TBI, although its role was very weak,” Zhu said. “Our data suggest that enhancement of this neuroprotective role of the liver could provide novel strategies for developing treatment of TBI.” Plans call for “moving toward a clinical study to detect whether hepatic sEH manipulation benefits patients with TBI.”
Their results highlight the neuroprotective role of the liver in TBI and suggest that targeting this neuroprotective role may represent a promising therapeutic strategy for TBI. Earlier clinical studies report that the overall mortality in patients with TBI and cirrhosis is nearly twice that in patients without cirrhosis.
In the paper, “Enhancement of the Liver's Neuroprotective Role Ameliorates Traumatic Brain Injury Pathology,” the authors describes TBI as a “pervasive problem worldwide, for which no effective treatment is currently available,” and “as a devastating injury that often results in long-term neurological deficits, including locomotor function and memory impairments.”
“Blood–brain barrier (BBB) disruption is a hallmark feature of TBI and is associated with brain edema and neuronal death,” the authors wrote. “Studies have shown that sEH inhibitors protect the BBB from brain injury. Therefore, we investigated whether deletion of hepatic Ephx2 protected the BBB following controlled cortical injury (CCI).”
“TBI leads to a breakdown of the blood brain barrier,” said co-author Hammock, a member of the National Academy of Sciences and the National Academy of Inventors and whose pioneering work on sEH inhibitors spans 50 years. “We see from cases like Muhammad Ali that repeated TBI can lead to chronic central nervous system injury, dementia and other issues.”
“In the study from the Zhu laboratory, one of the exciting basic discoveries is that mammals have a natural mechanism to partially address traumatic brain injury,” said Hammock, who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. “By a mechanism under investigation, the injured brain communicates to the liver to down-regulate the production of an enzyme called the soluble epoxide hydrolase (sEH) that degrades natural inflammation resolving mediators. Thus, the concentration of these injury-resolving mediators also produced in the liver go up reducing deleterious inflammation throughout the injured animal. This soluble epoxide hydrolase inhibitor used as a tool in these studies is building on this natural mechanism to minimize the harmful effects of TBI.”
"Importantly, the soluble epoxide hydrolase inhibitor that the authors used here is also currently in human clinical safety trials for treating pain and inflammation,” said psychiatrist and neuroscientist Dr. Andrew Pieper, the Rebecca A. Barchas Professor in Translational Psychiatry, Case Western Reserve University, Cleveland. “The results shown here indicate that this agent, or related materials altering this same pathway, might mitigate the acute and long-term complications of TBI, or of neuroinflammatory conditions of the brain in general. Pieper, who holds both a Ph.D. and a M.D.. is the Morley-Mather Chair in Neuropsychiatry, University Hospitals of Cleveland Medical Center; director of the Brain Health Medicines Center, Harrington Discovery Institute; and psychiatrist at Louis Stokes Cleveland VA Medical Center, Cleveland.
Neuroscience researcher Daniela Kaufer, associate dean of biological sciences at UC Berkeley and a professor with the Department of Integrative Biology and Helen Wills Neuroscience Institute, praised the research possibilities. “The brain has a barrier which helps protect it from harmful materials in the blood,” said Kaufer, who was not involved in the research. “TBI reduces this barrier and its reduction is associated with aging. Possibly the pathway described in this PNAS paper could be manipulated to protect the blood brain barrier and reduce the apparent aging of the brain caused by repeated TBI.”
“My understanding of how we classify milds at UC Davis right now is that these are patients that behaviorally are mild injuries, but that they have something on a CT or MRI scan that indicates that the injury is more than a concussion, said Gurkoff, who was not involved in the research. “These patients are more likely to have long-term effects than concussion alone, but a lot less likely than moderate-severe. They also don't usually end up in the ICU. Then there are the concussions. Head injuries but no evidence of a radiological finding.”
“Add on top of that, repeat mild or repeat concussion,” Gurkoff said. “While some investigators will suggest that we have a good handle on repeat TBI--I still think it is the Wild West. It is clear that in a subset of humans, repeat TBI, even concussive, is catastrophic. Others seem to be fine. We also haven't dissected whether repeat TBI on its own is causal --or because many of the patients are in high risk/high stress situations--and it is the combination of TBI/repeat TBI with something else.”
“What gets me excited about certain compounds--Bruce's would be an example--is that if you have a low-risk compound, is it feasible that you give it to patients who might not develop long-term consequences?” Gurkoff asked. “For example, let's say a patient comes in and based on his injury and history, we might estimate there is a 10 percent chance he has a problem. You aren't going to schedule these patients for surgery--on the extreme--because the risk is too high given they most likely will recover. Having a low-risk compound that can be given to soldiers, athletes, etc, with mild or repeat mild--or concussion/repeat concussion--would be fantastic!”
The research drew financial support from the National Natural Science Foundation of China, Scientific and Technological Innovation, and partial support from Hammock's grants from the National Institute of Environmental Health Sciences' RIVER Award (Revolutionizing Innovative, Visionary Environmental Health Research) and the National Institute of Neurological Disorders and Stroke.
“This pioneering study provides clear evidence of the importance of liver-derived epoxy fatty acids (EpFAs) and reactive astrocytes from the immune system in protecting the brain from significant damage and post-traumatic dysfunction following percussive injury,” said William Schmidt, EicOsis vice president of clinical development. “As of now, there are no proven drug therapies that provide protective effects to the brain following single or repeated blows to the head from falls, auto accidents, or sports injuries.”
“The data from this study,” Schmidt said, “provides a pathway for developing inhibitors of sEH that, in turn, will enhance the availability of EpFAs circulating in blood to protect and restore the blood-brain barrier following TBI. I am hopeful that further preclinical studies will confirm these data and lead to a new type of drug therapy based on inhibitors of the sEH enzyme.”
“Clinical studies for TBI may still be a year or so away,” Schmidt added, “but EicOsis has an sEH inhibitor in early clinical development that may be suitable in the future for evaluation in patients with TBI.”
Hammock and colleague Sarjeet Gill co-discovered sEH in 1969 when they were researching insect developmental biology and green insecticides in the UC Berkeley lab of John Casida (1929-2018).
The enzyme is a key regulatory enzyme involved in the metabolism of fatty acids. It regulates a new class of natural chemical mediators, which in turn regulates inflammation, blood pressure and pain. The epoxy fatty acids control blood pressure, fibrosis, immunity, tissue growth, depression, pain, and inflammation, to name a few processes, Hammock said.
Resources:
PNAS paper: https://doi.org/10.1073/pnas.
Traumatic Brain Injury, National Institutes of Health
Traumatic Brain Injury, Mayo Clinic
Contacts:
Bruce Hammock, PhD: bdhammock@ucdavis.edu
Irene Cortés-Puch, M.D., EicOsis: icortespuch@eicosis.com
- Author: Kathy Keatley Garvey
"Graduate Studies Class of 2023, you give us faith that a better tomorrow is possible," Chancellor May told them. "You are the innovators, the researchers, the scientists, the artists, the leaders and the visionaries of tomorrow. The world needs you and you have so much to offer."
"No matter what field is your specialty, UC Davis has prepared you for the next chapter," he continued, adding that "Each of you has one thing in common. You graduated from a world-class university that fully embraces intellectual curiosity and versatility."
The chancellor then asked the graduates to remember "three things":
- "You are not alone. You are an Aggie. You are part of a community of 290,000 members spanning the globe."
- "With a little imagination, collaboration and concerted effort, you can change the world."
- "Everyone has their own unique super powers. Continue to use yours for good."
Smiles, laughter, and cheers punctuated the event. Some of the graduates decorated their mortarboards. Entomology students favored insect antennae.
It was especially heartwarming for Charlotte Herbert Alberts, who enrolled in the UC Davis doctoral program in 2015. During her studies, she married her sweetheart, George Alberts, in 2018; moved cross-country in 2020 during the COVID pandemic; gave birth to two children (Griffin, now 3, and Marcy, 7 months); and published two of her dissertation chapters. The family lives in Silver Spring, Md.
Griffin could hardly wait to see "Mama become a Wizard." Following the commencement, he delighted in trying on what he called "Mama's Wizard Hat." The next day, when his grandparents asked him his favorite part of the ceremony, he quickly responded: "Watching Mama become a Wizard!"
"It was great closure to walk across the stage!" said Alberts, who enrolled in the entomology graduate program in 2015. "It was a non-linear adventure, with many bumps and hurdles along the way. But it's amazing feeling to finally cross the stage and be done! Especially with my parents, George, and my children watching! I couldn't have done it without their--and many others'--support! I currently work at the Smithsonian publishing my last two chapters of my dissertation. I'm applying to post docs in the fall and taking the summer to enjoy time with my kids as much as possible!"
Here are photos from the commencement shared by graduate students and professors.
- Author: Kathy Keatley Garvey
The three-pronged Chancellor's Award, launched in 1994, annually honors three outstanding mentors: a graduate student; a postdoctoral fellow or project scientist; and a faculty member.
Professor Chiu, who joined the faculty in 2010, focuses her research on the molecular and cellular biology of circadian rhythms and seasonal rhythms.
Chiu lab member and doctoral candidate Christine Tabuloc, who will be receiving her PhD this month, nominated her for the award. A team of five other Chiu lab alumni submitted a group letter of recommendation.
"I joined Dr. Chiu's laboratory at the beginning of my second year here at UC Davis and remained a member of the lab for 3 years as an undergraduate, 2 years as a technician, and 6 years as a graduate student," Tabuloc wrote. "Throughout all my time in the Chiu lab, Joanna has never failed to amaze me with her kindness, patience, and her consistency and perseverance in helping all students, both in her lab and in other labs, succeed. I cannot think of anyone more deserving of this award than Dr. Chiu."
"Dr. Chiu welcomed me into her lab back in 2012," Tabuloc related. "I had just finished my first year of college, and I had virtually no research experience. Despite this, Joanna took a chance on me and invited me to join her lab. Throughout the years, Joanna has taught me many skills—both at the bench and skills that translate outside the lab and even beyond academia. Joanna has taught me everything I know from performing an experiment with all the proper controls to mentoring students and giving effective and clear presentations. What makes her so outstanding is her commitment to helping us improve as scientists and researchers and preparing us for our future career endeavors."
Tabuloc praised Professor Chiu for teaching her effective communication, organization, time and personnel management, and resilience.
"One thing that I find unique about Joanna is her ability to see our potential before we even see it in ourselves," Tabuloc wrote. "Joanna often says that once we step into the doors of the lab, we are no longer students rather, we are scientists. She encourages us to think like scientists and gives everyone equal opportunity to pursue their scientific questions of interest and carry out independent projects."
"Not only have I experienced Dr. Chiu's mentorship first-hand, but I have also had the privilege of watching her mentor all the undergraduate students that have joined her lab throughout the years. In fact, since my time here, I have watched at least 35 undergraduates be mentored by Joanna, and many of these students were authors on publications in peer-reviewed journals such as Scientific Reports, Journal of Pest Science, BMC, Ecology, Current Biology, Nature Communications, Journal of Economic Entomology, and PLOS Genetics. More so, a true testament to her success as an undergraduate mentor are her students' successes: furthering their education at academic institutions such as Cornell, Stanford, Columbia, UCB, and UCLA or landing industry jobs at companies such as 10X Genomics. Many of these students still keep in contact with Dr. Chiu, and she continues to provide advice and guidance such as reviewing resumes and helping them prepare for interviews. Joanna is not just our mentor when we are at UCD, she is our mentor for life."
Group Letter. The former lab members who teamed to write the group letter, all praised her impactful influence--her mentoring, her encouragement, her constructive feedback, and her strong support:
- Lisa Soyeon Baik, now a postdoctoral fellow at the Carlson lab, Department of Molecular, Cellular, and Developmental Biology, Yale University
- Daniel Ewels-Labolle, PhD student at Cornell
- Jessica West, PhD student at Cornell
- Katherine "Katie" Freitas, PhD student at Stanford University
- Kiya Jackson, who received her bachelor's degree in biological sciences, then joined the UC Davis Postbaccalaureate Research Education Program, and will be heading to UCLA for her PhD
"She helped me to gain confidence and to envision myself as a scientist. She not only gave me a start in my scientific career, but her mentorship has far exceeded my time in her laboratory. She has continually supported me through graduate school and now as a postdoctoral researcher."--Lisa Soyeon Baik
"I can say without a shadow of a doubt that I would not have been able to get to where I am now without Joanna's mentorship, advice and overwhelming support."--Daniel Ewels-Labolle
"As a PhD student at Cornell, I am immensely grateful for the training I received as an undergrad from Dr. Chiu. Not only did she train me thoroughly in basic biochemistry and molecular biology techniques, but she also pushed me to be independent and think critically about my science, skills essential for graduate school."--Jessica West
"Beyond teaching me practical research skills, Dr. Chiu helped to spark the most important thing a person needs to be a successful scientist: pure joy in the pursuit of knowledge."--Katie Freitas
"I believe Dr. Chiu is a valuable mentor for undergraduate researchers because she offers her time and expertise to train well-rounded scientists, regardless of the stage at which they start their career and regardless of what career they hope to pursue."--Kiya Jackson
Chiu joined the Department of Entomology and Nematology in 2010 as an Assistant Professor, and advanced to Associate Professor and Vice Chair in 2016, and to Professor and Vice Chair in 2021. She was named one of 10 UC Davis Chancellor's Fellows in 2019, a five-year honor awarded to associate professors who excel in research and teaching. The UC Davis Academic Senate honored her with a Distinguished Teaching Award, Graduate/Professional category, in 2022.
Chiu co-founded and co-directs (with professors Jay Rosenheim and Louie Yang) the campuswide Research Scholars Program in Insect Biology, launched in 2011 to provide undergraduates with a closely mentored research experience in biology. The program's goal is to provide academically strong and highly motivated undergraduates with a multi-year research experience that cultivates skills that will prepare them for a career in biological research.
Chiu received her bachelor's degree in biology and music from Mount Holyoke College, Mass., and her doctorate in molecular genetics in 2004 from New York University, New York. She trained as a postdoctoral fellow from 2004 to 2010 in molecular chronobiology at the Center for Advanced Biotechnology and Medicine, at Rutgers, the State University of New Jersey.
- Author: Kathy Keatley Garvey
The research involves the development of a DNA-based sensor amplification system demonstrated in a fluorescence immunoassay that can detect, both simply and rapidly, trace amounts of organophosphate pesticides (OPs) in food products.
Trace detection of such OPs as triazophos, parathion, and chlorpyrifos is “extremely important for various reasons, including food safety, environmental monitoring, and national health,” the authors pointed out.
The device is not only easier to use, more reliable, and faster than traditional methods of pesticide detection, but offers a more cost-effective alternative, said the authors, noting that their device could “address the limitations of traditional detection methods, such as liquid chromatography-tandem mass spectrometry, which are expensive, time-consuming, and require extensive training.”
The paper, “Competitive Fluorescent Immunosensor Based on Catalytic Hairpin Self-Assembly for Multiresidue Detection of Organophosphate Pesticides in Agricultural Products,” appeared in the February edition of the Food Chemistry journal and is republished in June as “Paper of the Month."
Maojun Jin, who served a year (September 2019 to September 2020) as a visiting scholar in the Hammock laboratory, UC Davis Department of Entomology and Nematology, led the research team, and is the senior author and corresponding author. He is now a professor in the Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences. His doctoral student, Yuanshang Wang, is the first author.
“The immediate impact of the rapid biobar code immunoassay in reducing human and environmental exposure to three organophosphate pesticides is obvious,” said Hammock, who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. “Since Rosalyn Yalow shared the 1977 Nobel Prize for developing the immunoassay, there have been many incremental improvements to increase assay sensitivity and speed. The biobar code amplification system is more than incremental. It also allows samples to be multiplexed with several analytes monitored in one tube. This amplification technology can be applied to immunoassays in general in both the biomedical and environmental field. It is wonderful to see what Maojun and his team have accomplished. In analytical chemistry we are always striving for ‘better, faster, cheaper' and Maojun's team accomplished this.”
Hammock said that the aim is to “ensure proper use and protect human health from some commonly used and quite toxic pesticide and the development of a novel signal amplification - transduction system making the assay faster, more sensitive and allowing the assay to be multiplexed with the possibility of multiple signals in one tube with the use of DNA biobar codes.” In the paper, the co-authors point out that “The organophosphate pesticides triazophos, parathion, and chlorpyrifos are highly toxic and have been linked to adverse health outcomes, such as cancer. Although many countries have banned or restricted their use, the chemicals are still components of pesticide mixtures used in daily agricultural production around the world. The sensor contains an immunoassay, which is a type of test that uses antibodies to detect pesticide residues. This process results in a single DNA strand that then binds to a gold nanomaterial-based synthetic protein through chemical bonding.”
“Then, another DNA structure called a hairpin is added to the mix to from a double-stranded DNA structure,” they explained. “The resulting structure fluoresces upon detection of the residues so organophosphates can be quantified.”
The team then used the sensor to measure traces of OPs in contaminated fruit, vegetables, and grain and compared their results to findings from traditional liquid chromatography-tandem mass spectrometry. They found that their DNA-based sensor detected the three pesticides in the mixtures as accurately as the mass spectrometry method.
“I'm very proud of what Maoiun and his team have accomplished,” said Hammock, who directs the NIEHS-UC Davis Superfund Research Program. The research was partially funded by his Superfund grant, and his NIEHS RIVER (Revolutionizing Innovative, Visionary Environmental Health Research) Award.
In addition, the research drew financial support from the National Natural Science Foundation of China, Central Public-interest Scientific Institution Basal Research Fund, and the Central Public Interest Scientific Institution Basal Research Fund for the Chinese Academy of Agricultural Sciences.
Professor Jin is engaged in research on food safety testing technology, especially in immunoassay. “Firstly, we develop antibodies against different types of pesticides, including monoclonal antibodies, nanobodies, and recombinant antibodies,” he explained. “With these antibodies, we can specifically recognize pesticide residues in food and the environment. On the basis of preparing antibodies, we achieve quantitative detection of pesticide residues based on different labeling systems, such as colloidal gold, fluorescence, chemiluminescence, and DNA strands. This paper is based on DNA strands as marker substances, achieving the detection of very trace pesticides in food and ensuring human health.”
Yuanshang Wang is a doctoral student at Huazhong Agricultural University, specializing in food science. “My research interest is in the field of trace and rapid detection analysis of hazardous substances in food,” she said.
- Author: Kathy Keatley Garvey
The seminar also will be on Zoom. A pre-seminar coffee will take place from 3:30 to 4:10 p.m. in 158 Briggs.
"Ants of the genus Dorymyrmex, the 'pyramid ants,' exhibit an intriguing distribution that is most concentrated not near the equator, but instead in dry temperate regions of the Americas, such as deserts, shrublands, and beaches, and including Davis, California," Oberski writes in her abstract. "Although these ants are common, widespread, and ecologically significant, their diversity and evolutionary history are still poorly understood. My dissertation research introduces Dorymyrmex to modern phylogenomics and concerted biogeographic study by integrating classic and cutting-edge approaches: I performed targeted genomics with UCEs, inferred Bayesian phylogenies and fossil-calibrated divergence dates, and also employed traditional methods like morphometrics and visual species description."
"My work (1) characterizes the major lineages of Dorymyrmex, which are morphologically diverse in the Neotropics but actively peciating (and superficially similar) in North America; (2) illustrates an intercontinental range expansion that occurred millions of years ago; and (3) characterizes the Nearctic fauna, nearly doubling the number of Dorymyrmex species in North America. Ultimately, this research contributes to our knowledge of both local biodiversity and global dispersal patterns, and reveals Dorymyrmex is a unique system for studying rapid evolutionary radiations."
"I've been fascinated by insects as long as I can remember," Jill said. "As a kid, I learned the names of the major taxonomic orders and created a small pinned collection, but I didn't realize it could be anything more than a hobby, so I shifted my sights toward becoming a medical doctor. But when I went to college, I met a professor who actually does study biodiversity and discover new arthropod species for a living. So after getting my start in research at Macalester College, and a year as an intern at University of Wisconsin-Madison, I started searching for suitable research programs across the country where I could train as a grad student doing those same things—biodiversity, evolution, and biogeography of insects or arachnids."
"I was open to almost any insect/arachnid study system because generally, the more I learn about a group, the cooler I find it, and that turned out to be very true for ants. They're amazing little underappreciated creatures with societies all their own, and I'm so happy to be a myrmecologist."
Oberski is a past president of the UC Davis Entomology Graduate Student Association, and served in leadership roles in the Girls' Outdoor Adventure in Leadership and Science (GOALS).
Oberski received a five-year Dean's Distinguished Graduate Fellowship award in 2017. In May of 2022, she was selected for a Professors for the Future Fellowship (PFTF) award, described by PFTF as "a year-long competitive fellowship program designed to recognize and develop the leadership skills of outstanding graduate students and postdoctoral scholars who have demonstrated their commitment to professionalism, integrity, and academic service. The program is designed to prepare UC Davis doctoral students and postdoctoral scholars for an increasingly competitive marketplace and a rapidly changing university environment." For her project, she recorded a series of interviews about mental and chronic illnesses and how they impact academic professional development.
Oberski, who plays tenor saxophone at community events, performed in an entomology band at the 2018 UC Davis Picnic Day as Jill “Jillus Saximus” Oberski. She dressed as a “generalized heteropteran,” which she described as “most likely a member of the family Acanthosomatidae (shield bug) or Pentatomidae (stink bug). My family and friends have called me Jillybug, so I came to be the band's representative of Hemiptera.” (See news story on Entomology website, and feature in Entomology Today, published by ESA)
Future plans? After receiving her doctorate on June 15 in a UC Davis ceremony, Oberski will be moving to Washington, D.C. this summer for a brief stint as a visiting researcher at the Smithsonian Museum of Natural History. Then, in January 2024, she will start a three-year independent postdoctoral research position in Frankfurt, Germany.
The Oberski seminar is the last of the spring seminars, all coordinated by urban landscape entomologist Emily Meineke, assistant professor. For technical issues regarding Zoom connections, she may be reached at ekmeineke@ucdavis.edu.