- Author: Kathy Keatley Garvey
The controversial antibacterial chemical is grabbing nationwide attention with the recent cover story of “Triclosan Under the Microsope” in Chemical Engineering News. The article quotes Bruce Hammock, a UC Davis distinguished professor who holds a joint appointment in the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center.
“I'm getting love notes and hate mail,” he said, adding "“My colleagues and I are continuing to look at the positive and negative aspects of triclosan. It clearly has some negative effects on mammalian biology, but it is a very potent microbial and quite inexpensive, and relatively safe.”
Triclosan, first used in healthcare settings in the 1960s, is now found in products throughout the home—in everything from hand sanitizers, toothpastes, mouthwashes, deodorants and cosmetics to beddings, clothes, toys, carpets and trash bags.
Last month Minnesota became the first state to ban the ingredient in soaps and cleaning products. Other states concerned about the chemical's effects on human and environmental health may follow.
Hammock said that he and UC Davis colleagues molecular biologist David Mills and chemist Bruce German are now looking at the effects on gut bacteria.
“And, with Bob Tukey at UC San Diego, we are looking at enzyme induction in mammals and possible health risks,” Hammock said. Tukey, professor of pharmacology and chemistry and biochemistry, directs the UCSD Superfund Basic Research Program, while Hammock directs the UC Davis Superfund Program.
The U.S. Environmental Protection Agency in 1998 estimated that the U.S. produces more than 1 million pounds of triclosan annually, and that scientists can detect the chemical in waterways, aquatic organisms, and in human urine, blood and breast milk.
Concern over the controversial compound is swirling with the June 23rd publication of “Triclosan Under the Microscope.”
Hammock told author Jyllian Kemsley that when medical providers first started using triclosan as a surgical scrub, “it replaced some really scary compounds.”
He said that “Triclosan is much less toxic, more effective, and more biodegradable” than hexachlorophene and other common biocides of the time.
Wrote Kemsley: “But then triclosan made its way out of the operating room and into mass consumer products. In that context, its toxicity profile and environmental lifetime make the cost-benefit analysis murkier.”
“To me that doesn't say rush out and ban it,” Hammock told her, advocating careful consideration for mass use. He said washing hands with plain soap and water will likely fit most needs. Triclosan is a very effective anti-microbial but probably it is overused in many cases.
Kemsley wrote that some people may be more susceptible to harm, “such as those with genetic variations that reduce their ability to metabolize triclosan, leaving them with higher blood concentrations.” Some scientists worry if the toxicity level is worth it to reduce disease and also whether it promotes drug resistance.
Kemsley drew attention to the 2012 UC Davis study that shows that triclosan hinders cardiac and skeletal muscle contraction in mice and fish. The study, published in the Proceedings of the National Academy of Sciences (PNAS) and authored by a 13-member research team headed by Isaac Pessah and Nipavan Chiamvimonvat of the School of Veterinary Medicine and Hammock, found that triclosan hinders muscle contractions at a cellular level, slows swimming in fish and reduces muscular strength in mice.
“The effects of triclosan on cardiac function were really dramatic,” Chiamvimonvat, professor of cardiovascular medicine, related following the PNAS publication. “Although triclosan is not regulated as a drug, this compound acts like a potent cardiac depressant when administered at high doses in our models.”
- Author: Kathy Keatley Garvey
Titled “The Role of EETs in Pressure-induced Vasoconstriction,” the podcast explains the ground-breaking research involving the role of EETs (Epoxyeicosatrienoic acids) in regulating the myogenic tone in a skeletal muscle small resistance artery. The research, done on rodents, could lead to better control of high blood pressure in humans.
In the podcast, associate editor Mordy Blaustein interviews lead author An Huang (New York Medical College) and expert David Harder (Medical College of Wisconsin) about what Blaustein describes as “an innovative knock-out mouse model, responses of different types of vascular beds to various vasodilatory agents, and the importance of basic studies on SEH inhibitors as the backbone of clinical trials.”
EETs possess cardioprotective properties that are “catalyzed by soluble epoxide hydrolase (sEH) to dihydroxyeicosatrienoic acids (DHETs) that lack vasoactive property,” the seven-member scientific team wrote in their research, Soluble epoxide hydrolase-dependent regulation of myogenic response and blood pressure, published April 15 in the American Journal of Physiology-Heart and Circulatory Physiology.
“To date, the role of sEH in the regulation of myogenic response of resistant arteries, a key player in the control of blood pressure, remains unknown,” they wrote in their abstract. “To this end, experiments were conducted on sEH-knockout (KO) mice, wild-type (WT) mice, and endothelial nitric oxide synthase (eNOS)-KO mice treated with t-TUCB, a sEH inhibitor, for 4 wk. sEH-KO and t-TUCB-treated mice displayed significantly lower blood pressure, associated with significantly increased vascular EETs and ratio of EETs/DHETs. Pressure-diameter relationships were assessed in isolated and cannulated gracilis muscle arterioles. All arterioles constricted in response to increases in transmural pressure from 60 to 140 mmHg. The myogenic constriction was significantly reduced, expressed as an upward shift of pressure-diameter curve, in arterioles of sEH-KO and t-TUCB-treated eNOS-KO mice compared with their controls. Removal of the endothelium, or treatment of the vessels with PPOH, an inhibitor of EET synthase, restored the attenuated pressure-induced constriction to the levels similar to those observed in their controls but had no effects on control vessels. No difference was observed in the myogenic index, or in the vascular expression of eNOS, CYP2C29 (EET synthase), and CYP4A (20-HETE synthase) among these groups of mice. In conclusion, the increased EET bioavailability, as a function of deficiency/inhibition of sEH, potentiates vasodilator responses that counteract pressure-induced vasoconstriction to lower blood pressure.”
Lead author An Huang is with the Department of Physiology, New York Medical College, Valhalla.
In addition to Huang and Hammock, who has a joint appointment with the UC Davis Comprehensive Cancer Center, the co-authors are Sung Hee Hwang of the Hammock lab; Dong Sun, Department of Physiology, New York Medical College, Valhalla; Azita J. Cuevas and Michal L. Schwartzman, both with the Department of Pharmacology, New York Medical College, Valhalla; and Katherine Gotlinger, New York University School of Medicine, Tuxedo.
Grants from the by National Institutes of Health supported the research.
- Author: Kathy Keatley Garvey
Then it was Thomas Sparks in 2012
Now it's Keith Wing in 2014.
They're all linked together not only because each received the prestigious International Award for Research in Agrochemicals, sponsored by the American Chemical Society, but because they all once worked together at the same time in the Hammock lab.
Hammock, distinguished professor of entomology with the UC Davis Department of Entomology and Nematology and formerly a UC Riverside faculty member, was the first-ever recipient of the award, which is co-sponsored by BASF Corporation and DuPont Crop Protection.
"Keith got his Ph.D. in entomology from UC Riverside but did most of his Ph.D. work in the entomology department here (UC Davis) where he also was a postdoc," Hammock recalled. Wing worked in the Hammock lab from 1976 to 1980 at UC Riverside, and from 1980 to 1981 at UC Davis.
Sparks, who now lives in Greenfield, Ind., was Hammock's first graduate student at UC Riverside and later worked in his lab at UC Davis. “Tom was instrumental in the discovery and development of a new class of insecticides called spinosids,” Hammock said.
Wing, of the greater Philadelphia area, formed Keith D. Wing Consulting, LLC, in January 2012. He specializes in agriculture, renewable chemicals and life science clients, domestic or international, including biotechnology companies and the United Soybean Board (management of six renewable chemistry projects from soy residues).
Wing worked for E. I. DuPont, Wilmington, Del. from 1990-2011, advancing to team principal investigator and technical lead for Saccharification Enzymes. As a DuPoint employee, Wing received a number of the company's agricultural products global technology accomplishment awards in his search for safer pesticides.
Prior to joining DuPont, he was a senior insect physiologist of Rohm and Haas Co., Spring House, Pa., for seven years.
Wing studied at four UC institutions: UCLA, Berkeley, Riverside and Davis. He received his bachelor's degree in biology, specializing in entomology and physiology, from UCLA, summa cum laude, in 1976. He worked on his doctorate at UC Riverside and UC Davis from 1976 to 1981 with Professor Hammock, studying insect biochemistry/entomology and specializing in insect physiology and toxicology. Wing's dissertation: "Juvenile Hormone Esterases of Trichoplusia ni and other Lepidoptera: Characteristics, Site of Synthesis, Interaction with Other Proteins and Inhibition."
After receiving his doctorate, Wing worked at both UC Davis and UC Berkeley. His second postdoctoral research entomologist position was from 1981 to 1983 in Professor John E. Casida's pesticide chemistry and toxicology lab at UC Berkeley.
- Author: Kathy Keatley Garvey
DAVIS--Graduate student researcher Sean Kodani of the Bruce Hammock lab, University of California, Davis, has received a fellowship to study omega 3 fatty acids.
The fellowship is from the Center for Content Rich Evaluation of Therapeutic Efficacy (cCRETE), headed by Katherine Ferrara, a distinguished professor and director of the Department of Biomedical Engineering and a newly selected member of the National Academy of Engineering.
The center, cCRETE (pronounced "secrete") is part of the Research Investments in Science and Engineering (RISE) Program.
Kodani's projects will involve continuing the work of Guodong Zhang, who recently received a faculty position at the University of Massachusetts, Amherst. While at Davis, Zhang found that metabolites of omega 3 fatty acids reduced angiogenesis, tumor growth and tumor metastasis. "I will be focusing on the specific pathways involved in this phenomena while also investigating the biological activity of other omega 3 metabolites," Kodani said.
"When I first rotated in Dr. Hammock's laboratory I mostly synthesized inhibitors for the enzyme soluble epoxide hydrolase, which is the primary target investigated in our laboratory," Kodani said. "However, my background is stronger in biology and biochemistry than synthetic chemistry, so when I joined the laboratory this was a project where I could incorporate all of those skills."
Kodani, from Orangevale, received his bachelor's degree in molecular toxicology and environmental sciences from UC Berkeley in 2012.
In addition to Ferrara, the leadership of cCRETE includes
- Steven C. Currall, dean and professor of Management Graduate School of Management
- Ralph deVere White, director of the UC Davis Comprehensive Cancer Center and distinguished professor of Urology
- Fredric Gorin, professor and chair of the Department Neurology
- Bruce Hammock, distinguished professor, Department of Entomology and Nematology with a jointappointment in the UC Davis Comprehensive Cancer Center
- Alexander Revzin, associate professor. Department of Biomedical Engineering, and
- Clifford Tepper, associate research biochemist, Department of Biochemistry and Molecular Medicine
The center focuses on assays of cell-secreted factors in vitro and in vivo, including exosomes, peroxide, and matrix metalloproteinases (MMPs). Cell secreted factors are of interest in 1) gauging the response to therapy with new drugs and 2) the development of an understanding of cell-to-cell communication. The “rich” content to be assessed to understand the impact of cell secretions goes beyond the quantification of traditional markers such as proliferation and apoptosis to evaluate markers of invasive potential, inflammation, “stem-ness,” autophagy and metabolic pathways.
"With respect to the response to therapy, the cost of bringing a new drug to market is now estimated to exceed $1 billion, with the timeline for developing a drug and getting it to market approaching 15 years," according to the website. "During the next 4 years, 9 of the top 10 and 18 of the top 20 best-selling drugs in the world will go off patent. A major challenge for the pharmaceutical industry is their lack of tools to identify promising candidates and to separate the winners from the losers early in the development process. Such tools have the potential to substantially reduce the cost to market for new drugs. To address the critical need for screening tools, a team of cancer biologists, social scientists, bioinformatics experts and bioengineers has formed a single disciplinary group to develop and validate biomarker assays for the effect of new therapeutics.
"In addition, members of the group (Hammock, Gorin, Ferrara) have developed novel therapeutics that effectively inhibit key pathways in cancer and atherosclerosis; the success of these new therapeutics will require biomarkers, which are one focus of our team. Therefore, one important problem to be solved is the creation of high throughput and content rich assays to summarize the impact of therapeutics on cellular functionality. We are developing in vitro cell microsystems where micropatterned co-cultures of cancer and non-cancer cells are juxtaposed with arrays of sensing elements for monitoring downstream readouts of cell-drug interactions. Further, we are developing and applying in vivo imaging approaches to assess specific targets and efficacy."
Hammock holds a joint appointment in the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. He directs the campuswide Superfund Research Program, National Institutes of Health Biotechnology Training Program, and the National Institute of Environmental Health Sciences (NIEHS) Combined Analytical Laboratory.
- Author: Kathy Keatley Garvey
DAVIS--Cancer biology researcher Amy Rand, a postdoctoral researcher in the Bruce Hammock lab at the University of California, Davis. has been selected a fellow in the T32 Postdoctoral Training Program in Oncogenic Signals and Chromosome Biology.
“I will be looking at how metabolites of omega-3 fatty acids can protect against cancer,” Rand said. “A previous researcher in the Hammock lab was the first to find a specific metabolite that inhibited the formation of blood vessels which then suppressed the formation and spread of tumors. I aim to further explore the specific mechanism that links omega-3 fatty acid metabolism and their anti-cancer activity.”
“Omega-3 fatty acids are increasingly being used as dietary supplements, and are marketed for their many beneficial health effects,” she said, in explaining the significance of the project. “This research will help us to further clarify the specific relationship between the dietary exposure to and metabolism of omega-3 fatty acids and their role in the regulation of certain cancers.”
Wolf-Dietrich Heyer, professor and chair of the Department of Microbiology and Molecular Genetics and director of the T32 Training Grant in Oncogenic Signals and Chromosome Biology, praised Rand for her excellent qualifications, research plan and presentation. "We are confident that your postdoctoral studies in Dr. Hammock's laboratory will lead to significant new insights in cancer biology."
Her future goals? “I have a growing interest in research that lies at the interface between chemistry and biology. Becoming an academic researcher is something I would love to pursue; it would be a fantastic opportunity to explore the relationship between the dietary exposure and metabolism of chemical substances and their corresponding biological activity.”
Long interested in a scientific career, Rand said she's had several inspiring teachers, who played “a big role in my developed interest in the sciences. Becoming a scientist was attractive to me because you use a combination of critical thinking, observation, creativity, and patience to answer important questions. It's very satisfying to work hard at accomplishing a piece of the research puzzle, and then communicating the story that surrounds its significance.”
Rand, from Halifax, Nova Scotia, received bachelor degrees in music and chemistry from Mount Allison University, New Brunswick, in 2007 and her doctorate in environmental chemistry from the University of Toronto in 2013.
Hammock holds a joint appointment in the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center. He directs the campuswide Superfund Research Program, National Institutes of Health Biotechnology Training Program, and the National Institute of Environmental Health Sciences (NIEHS) Combined Analytical Laboratory.
