- Author: Kathy Keatley Garvey
The 12th annual Bruce Hammock Lab Water Balloon Battle will take place at 3 p.m., Thursday, July 24 on the north side of the Briggs Hall lawn.
Christophe Morisseau, associate research scientist, said the lab has 2000 water balloons to fill; anyone who wants to be a water warrior must participate in the filling, which starts at 1 p.m. by the Briggs loading dock.
All are invited. “Whoever wants to get wet,” Morisseau said. “Children and spouses are always welcome.”
In the past, the water warriors, led by Bruce Hammock and Morisseau, have included professors, researchers, visiting scientistis, postdoctoral scholars, graduate students and undergraduate students.
In addition to the water balloons, some favor squirt guns and toy pressurized water blasters. Others hoist half-filled buckets of water for sneak attacks.
So proficient are the water warriors that the “15 minutes of fame” often turns into “10 minutes of aim.”
Hammock, a distinguished professor of entomology who holds a joint appointment with the UC Davis Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center, launched the water balloon fest in 2003 as a way to build camaraderie and gain relief from the heat.
The Hammock lab works hard and plays hard. Hammock, a member of the National Academy of Sciences and a fellow of the Entomological Society of America, 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.
DAVIS--Researchers at UC Davis, University of Massachusetts and Harvard Medical School have created a combination drug that controls both tumor growth and metastasis. By combining a COX-2 inhibitor, similar to Celebrex, and an epoxide hydrolase (sEH) inhibitor, the drug controls angiogenesis (blood vessel formation), limiting a tumor's ability to grow and spread. The study appears July 14 in the journal Proceedings of the National Academy of Sciences.
“We've been studying the effects of COX and sEH inhibitors, both by themselves and in combination, for several years,” said senior author and UC Davis Distinguished Professor Bruce Hammock. “We were surprised to find that the dual inhibitor was more active than higher doses of each compound, either individually or together. By combining the two molecules into one we got much greater potency against several diseases and completely unique effects in terms of blocking tumor growth and metastasis.”
Both COX and sEH enzymes control lipid signaling, which has long been associated with inflammation, cell migration, proliferation, hypertension and other processes. COX inhibitors block production of inflammatory and pain-inducing lipids, while sEH inhibitors preserve anti-hypertensive, anti-inflammatory and analgesic compounds. Separate COX and sEH inhibitors were previously found to work together in reducing inflammation and neuropathic pain.
After testing individual COX-2 and sEH inhibitors, the team synthesized the drug (PTUTB), the first combined COX-2/sEH inhibitor. They then tested the dual inhibitor against human lung and breast tumors, both in vitro and in mice. They found that PTUTB blocked angiogenesis, inhibiting the proliferation of endothelial cells, which are critical to blood vessel formation. This in turn limited tumor growth and metastasis, reducing lung and breast tumor growth by 70 to 83 percent.
In breast and lung cancers, the dual inhibitor blocked angiogenesis, which blocked the growth of solid tumors,” said Hammock. “This represents a new mechanism to control blood vessel and tumor growth.”
“This is particularly important when administering COX-2 inhibitors, which have well-known cardiovascular risks,” he said. “However, the added sEH inhibitor appears to block COX-2's side effects.”
The research was initiated by first author Guodong Zhang when he was a postdoctoral fellow in the Hammock laboratory. Zhang previously demonstrated that sEH inhibitors improve the power of omega-3 fatty acid (fish oil) diets to reduce tumor growth and metastasis, and implicated epoxides of the dietary supplement DHA as the causative agent.
By advancing a new anti-angiogenic compound, the study extends the work of renowned Harvard Medical School physician and researcher Judah Folkman, who illuminated the importance of angiogenesis to tumor growth, inspiring a new class of anti-cancer drugs. Two of the study's authors, Dipak Panigrahy and Mark Kieran, previously worked with Folkman at Harvard Medical School.
Though the research was focused exclusively on cancer, researchers said the dual compound could benefit other conditions, such as macular degeneration.
“If we move beyond cancer, this drug combination could block a number of pathologies, ranging from cardiac hypertrophy to neuropathic pain,” said Hammock. “The compound looks quite powerful for a number of conditions.”
The research teams are continuing their work on several fronts.
“One member of our research team already has made more potent inhibitors with more drug-like properties,” Hammock said. “We are looking at the molecules for a variety of indications alone and in combination, including for kidney disease, fibrotic diseases, pancreatic and colon cancer and other problems.” The molecules are patented by the University of California and are available for license and testing.
Co-author Jun-Yan Liu, who performed the analytical chemistry for the study while a postgraduate researcher at UC Davis, is now examining the efficacy of the compounds in kidney disease and gout at a laboratory in the Shanghai Tenth Peoples Hospital.
“One of the most exciting things about this project was the ability to work with experts in multiple fields to find new drug class and new mechanism that promises to actually help people with cancer,” Liu said.
Other researchers included Sung Hee Hwang, Jun Yang, Lisa M. Mahakian, Yanru Wang, Elizabeth S. Ingham, Sarah Tam, Robert H. Weiss and Katherine W. Ferrara, all of UC Davis, and Hiromi I. Wettersten, formerly of UC Davis and now at UC San Diego.
The research was supported by NIEHS R01 ES02710, Superfund P42 ES04699, NIH/NIOSH U54 OH07550, R01 CA134659, R01 CA112356, R01 CA103828, NIH contract HHSN268201000043C, Research Investments in the Sciences and Engineering (RISE) Program of UC Davis, R01 CA148633, R01 CA135401, R01 DK082690, the Stop and Shop Pediatric Brain Tumor Fund, the C.J. Buckley Pediatric Brain Tumor Fund, the Medical Service of the US Department of Veterans Affairs and the American Asthma Society.--UC Davis Comprehensive Cancer Center, UC Davis Health System Public Affairs
(Editor's Note: Bruce Hammock has a joint appointment with 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
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.