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A rhesus macaque juvenile enjoying one of the many enrichment objects provided to the outdoor-housed monkeys.
A rhesus macaque juvenile enjoying one of the many enrichment objects provided to the outdoor-housed monkeys.
June 26, 2014  

Improving models to understand the etiology of autism, and develop early intervention and treatments

Using an exciting, first of its kind method and making great strides in understanding the biology of autism, Sara Freeman, PhD, postdoctoral researcher at the CNPRC, is the first develop a novel protocol using selective oxytocin receptor ligands to locate and map oxytocin receptors in rhesus monkey brains (“The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta)”, Freeman et al, Psychoneuroendocrinology, July:45:128-141, 2014).

Dr. Freeman has also mapped the oxytocin receptor and the closely related vasopressin 1a receptor in brain tissue from the titi monkey (“Neuroanatomical distribution of oxytocin and vasopressin 1a receptors in the socially monogamous coppery titi money (Calicebus cupreus)”, Freeman et al, Neuroscience, July:273:12-23, 2014). Titi monkeys are small, monogamous monkeys originating in South America, and the colony at the Center is the only one of its kind in the world. Titis are involved primarily in biobehavioral studies of attachment and parental behavior and are used to understand the role of oxytocin in social behavior.

Dr. Freeman found that these two nonhuman primate species express the oxytocin receptor in areas that are important for visual, auditory, and multimodal sensory processing. This distribution is distinct from rodent brain tissue, where oxytocin receptors are concentrated in areas that process olfactory information. The hormone oxytocin is well known by scientists to play an important role in social behavior: promoting trust and cooperation and making people more attuned to social cues. This research provides insights into the neural mechanisms by which oxytocin modulates social cognition and behavior in primates, which, like humans, uses vision and audition as the primary modalities for social communication.

Dr. Freeman is also using titi monkeys to evaluate an innovative protocol to noninvasively map the oxytocin receptors using PET scanning technology. The information gained from the titi monkey studies has led to a fascinating investigation in which Dr. Freeman is planning to use the same novel techniques to identify receptor locations in brain tissue from normal and autistic humans. These techniques will for the first time inform us where the human brain has these important receptors and may ultimately develop into a diagnostic approach.

With the prevalence of autism currently at 1 in 68 births, Autism Spectrum Disorder is now the fastest growing developmental disability in the US, with over $60B in annual costs. In 10 years, the projected annual cost will be $200-400 billion. Yet, with early diagnosis and intervention, the cost of lifelong care can be reduced by 60% with early diagnosis.

Dr. Karen J. Parker, Stanford University Medical School professor of psychology and CNPRC Affiliate Scientist conducting research in the translational social neuroscience of autism, emphasizes the importance of this research "Development of state-of-the-art imaging tools to locate oxytocin receptors in the living monkey brain has extraordinary translational potential to help identify the patients most likely to benefit from oxytocin treatment."

The rhesus macaque and titi monkey are important primate models for social behavior, and recent studies have begun to explore the impact of oxytocin on social cognition and behavior. Similar to humans, macaques and titi monkeys naturally show a spectrum of sociality and have great potential for elucidating the neural mechanisms by which oxytocin modulates social cognition, which has implications for oxytocin-based pharmacotherapies for psychiatric disorders such as autism and schizophrenia.


April 16, 2014  

Primate Models in Research
Scientists discuss the importance of primate models for advancing knowledge in biomedical and biological research

Presenting an honest, forthright discussion of the ethical considerations of using nonhuman primates (NHP) in research, and demonstrating the vital role NHP have played in many of the medical and scientific advances of the past century, 14 scientists, including CNPRC researchers Drs. Karen Bales, John Capitanio, and Lisa Miller, collaborated to publish a comprehensive article in the American Journal of Primatology entitled “Why Primate Models Matter” on April 15, 2014 (Early View).

Addressing some of the current topics of research with NHP, Dr. Kimberley Phillips, Department of Psychology, Trinity University, San Antonio, Texas and her co-authors discuss how NHP animal models are ideal for studying: atherosclerosis, behavior, cognition and language, cognitive aging, developmental programming, genetics, HIV/AIDS, immunology, neuroscience, pharmacology, reproduction, and respiratory diseases.

Nonhuman primates and humans have a high degree of biological similarity in their neurology, immunology, reproduction, and development, and there are many diseases and conditions that can only be studied in NHP. Nonhuman primates provide scientists and physicians with irreplaceable opportunities to understand, treat, and prevent these human diseases and disorders.

Yet, because NHP are so very similar to us, the use of these animals in research must be carefully considered and conducted in a controlled and thoughtful manner.

To address these issues, the authors are among the scientists that are advancing and exceeding standards of NHP care by carefully considering the animal’s needs beyond food, housing, and veterinary care, and giving substantive attention to the issues of NHP cognitive and psychological needs. The authors write “Efforts are now made to enhance psychological well‐ being through social housing, addressing the specific social and development needs of infants and aged individuals, and providing environmental enrichment.”

Thanks to NHP research, German measles, polio, typhoid fever, yellow fever, and many other diseases are very rare today. Major medical advances have been made in treating heart disease, AIDS, cancer, diabetes, asthma, influenza, malaria, and others, making these diseases more survivable. Newly emerging global infectious diseases (Ebola, SARS, Marburg, avian and swine influenzas) continue to threaten our health. NHP researchers are working to develop treatments and cures for the above diseases and conditions, as well as Parkinson’s disease, Alzheimer’s, cystic fibrosis, multiple sclerosis, obesity, arthritis, infertility, aging, and others.

According to the authors, “we are at a critical crossroads in our society and unless NHP research is given the philosophical, emotional, and financial support and infrastructure that is needed to sustain it and grow, we are in danger of losing irreplaceable unique models and thus, our ability to continue to explore and understand, and develop preventions and treatments for numerous conditions that inflict great suffering on humans”.

These researchers are making significant progress in improving human and animal health, and animal welfare, at their research facilities worldwide. They are from the California National Primate Research Center (NPRC), Southwest NPRC, Yerkes NPRC, WaNPRC, and Wisconsin NPRC, Wake Forest University School of Medicine; Rijswick, The Netherlands; the UC Davis School of Veterinary Medicine and Department of Anatomy, Physiology and Cell Biology; Neuroscience Institute and Language Research Center, Georgia State University; Center for Pregnancy and Newborn Research, University of Texas Health Science Center; Baylor College of Medicine, Texas; and Wake Forest University School of Medicine.


April 15, 2014  

Dietary Sugar Affects Oocyte Maturation
Research links sugar consumption to disrupted ovarian function in healthy animals

CNPRC housed rhesus monkeys fed relatively low doses of dietary sugar over 6 months showed significant impairments in oocyte maturation and major changes in early embryo gene expression, according to researchers Charles L. Chaffin, PhD (University of Maryland School of Medicine), Catherine VandeVoort, PhD (CNPRC Reproductive Sciences and Regenerative Medicine Unit), and colleagues. The research was published April 14, 2014 in Endocrinology; "Dietary sugar in healthy female primates perturbs oocyte maturation and in vitro pre-implantation embryo development" (Charles L. Chaffin, et al).

Compared with control animals, primates fed the sugar supplemented diets showed no difference in menstrual cycle length or number of oocytes recovered following controlled ovarian stimulation and human chorionic gonadotropin (hCG). However, after an ovulatory hCG bolus, similar to that given in fertility clinics, 86% of the oocytes recovered from the control animals matured (achieved metaphase II (MII) of meiosis, critical for fertilization) compared with only 18.5% of the sucrose-treated animals. The rate of maturation to MII following hCG in human IVF typically ranges from 60%-80%.

While the sucrose treatments appeared to reduce the ability of the oocytes to resume meiosis, there was no difference between the rate of fertilization and progression to the blastocyst stage in vitro between control animals and sucrose-treated animals.

Sugar intake, even at lower levels than most women in the U.S. typically consume, appears to impact oocyte and early embryo development in healthy primates, the researchers concluded.

While sugar's role in human embryo development has not previously been shown and more research is necessary to understand any possible implications for human fertilization and child development, this early research in primates should not be ignored by women or their doctors, Dr. Chaffin advised.

"High sugar diets rich in refined carbohydrates have negative consequences for women, and we may have to extend this to consider that there might be consequences for their offspring as well," he said.

Almost nothing is known about the effects of sugar intake by healthy, non-obese women on the oocyte prior to fertilization, the researchers noted.

"The 'Western pattern diet' includes high percentages of refined carbohydrates representing more than 15% of the total caloric intake; this translates to more than 100 g per day," they wrote. "Thus, although healthy women of reproductive age may not be diabetic, consumption of highly refined carbohydrates and sugars could produce frequent periods of transient hyperglycemia with unknown effects on the ovary."

Dr. Chaffin said the idea to test the hypothesis that sugar impacts early oocyte maturation and embryo development came from earlier studies performed at the CNPRC by Dr. VandeVoort, when she used sugar as the control in an alcohol and fertility study involving rhesus monkeys, and found that the animals in the sugar arm of the trial had "strikingly abnormal" oocytes.

Adult female rhesus monkeys at the CNPRC, ranging in age from 6 to 12 years who were normal weight with regular menstrual cycles, were fed either a standard diet of high-protein monkey chow (with approximately 5.2 g of sucrose and 0.2 g of glucose per day) (control) or the standard diet plus 2.6 g of sucrose / kg of body weight twice a week for 6 months (sucrose-treated).

"Each dose was equivalent to approximately 180 g for an average weight woman in the U.S., with the weekly dose less than half that consumed by women," the researchers wrote. "Dosing was continued through the cycle of controlled ovarian stimulation, but ended prior to the administration of anovulatory hCG stimulus."

The researchers demonstrated that the effects of sucrose treatment were carried from the immature oocyte to the pre-implantation embryo by stopping sucrose treatment prior to the ovulatory stimulus, and coupling these oocytes with standard in vitro fertilization and embryo culture. They note that "Sucrose treatments reduced the ability of oocytes to resume meiosis, although in the oocytes that did mature, there were only a limited number of genes whose expression was altered by sucrose."

Dr. VandeVoort remarks that using the nonhuman primate model is critical for studies that cannot ethically be performed in humans.  Also, humans and nonhuman primates share many aspects of oocyte maturation that cannot be replicated in rodent models, because some of the biological processes are not the same in rodents as in primates.

"I think there is plenty of reason for caution here, even though we may not really understand the implications of these data for many years," Dr. Chaffin said.

This research was funded by the NIH Office of Research Infrastructures Programs and NIH - NIAAA.


February 28, 2014  

State-of-the-Art Respiratory Disease Center

The newly completed CNPRC Respiratory Disease Center (RDC) held an open house on February 27th to celebrate the construction of a state-of-the-art 19,000 square-foot wet laboratory and inhalation exposure facility that will set the standards for research in respiratory health.

The CNPRC has been a leader in understanding primate lung development and function for more than 30 years. It has the distinction of being the only National Primate Research Center (NPRC) with a Respiratory Diseases research unit, with scientific expertise in airway immunity, environmental air pollutants, pediatric pulmonary disease, and asthma. The CNPRC developed the first rhesus monkey model of adult and childhood asthma using a human allergen, which has given researchers the ability to test numerous biological mechanisms and new therapies.

More recently the CNPRC has conducted research projects that include a diversity of cross-disciplinary and collaborative topics: experimentally establishing an association between early life exposure to air pollutants and long-term airway disease; discovering a link between temperament and asthma; and developing new links between environmental tobacco smoke exposure and adverse effects on lung development, cognitive function, and brain development.

Ongoing research includes: critical research into the effects of Bisphenol A on lung development; work to identify mechanisms that limit pediatric defenses against viruses and bacteria in the lung; and investigation of the lung microbiome.

The RDC is the only facility of its kind in the nation, and will provide for the expansion of current capabilities and enhance the scope of collaborative research projects that can be conducted at the Center.

Louise Olsen, Inhalation Exposure Facility manager, also notes that the specially designed chambers will make future research projects more efficient than the old chambers with the ability to conduct multiple studies simultaneously.

Initial areas of investigation that will utilize the new inhalation exposure facilities include chronic obstructive pulmonary disease, pediatric exposures to environmental air pollutants, childhood asthma, and infectious diseases.

The Respiratory Disease Center will be available for use by researchers across the country studying lung diseases and conditions. It replaces labs built more than 30 years ago, providing space for both long-running collaborations and new ventures with researchers from UC Davis and other institutions.

“We’re absolutely thrilled to be opening this building,” said Lisa Miller, an associate professor in the School of Veterinary Medicine and CNPRC Respiratory Diseases Unit Leader, during a media tour held Thursday. “From a technical side, this is fantastic facility to study environmental exposures using the nonhuman primate as a model.”

Media coverage of this event can be viewed at:
Davis Enterprise:

Channel 13:

Capital Public Radio:

Sac Bee:


February 11, 2014  

Using Monkey Social Systems to Predict Banking Crises

A fascinating collaboration was recently conducted between disparate interests: the CNPRC, UC Davis’ Department of Statistics and Department of Economics, the International Institute for Human-Animal Networks, and the Department of Population Health & Reproduction at the School of Veterinary Medicine.

In a study comparing the behaviors of outdoor-housed rhesus macaque monkeys with banking industry activities, the researchers propose that tools developed to predict instability in monkeys’ social systems can provide an early warning system of an impending crisis in human societies, and that such crises are caused by breakdowns in internal networks rather than by disabling external forces. Catastrophic collapses could be avoided by monitoring changes in these key internal networks, they suggest.

“Admittedly, comparing monkeys to a financial system is unconventional, however, we believe the comparison is compelling,” said Fushing Hsieh, a professor of statistics and the study’s lead author.

“We argue that it’s possible to detect when a crisis is likely to set in -- whether in a primate social group or an industry like banking -- by modeling the evolution of the breakdowns across the system’s networks,” said co-author Òscar Jordà, a UC Davis economics professor and research advisor to the Federal Reserve Bank.

Dr. Brenda McCowan, Core Scientist in the CNPRC Brain, Mind, and Behavior Unit, and Program Head of Behavior Management, and Dr. Brianne Beisner, CNPRC and School of Veterinary Medicine Project Scientist, collaborated on the publication that addressed this question in the International Journal of Forecasting (e-pub Jan. 2, 2014, “Computing systemic risk using multiple behavioral and keystone networks: The emergence of a crisis in primate societies and banks”, H. Fushing, O. Jordà, B. Beisner, and B. McCowan).

Studying the rhesus macaque societies at the CNPRC, they applied these tools to primate social systems, which were observed under both stable and unstable states or phases. Interestingly, these primate social systems have many points of commonality with the architecture of a banking system.

Drs. McCowan, Beisner, and colleagues have shown that the individuals or “nodes” in monkey social systems relate to each other through multiple and keystone networks (aggression, affiliation, alliance networks, and the keystone network: status signaling) not just one network. Similar to a banking system, each network in the system has its own topology, and the interactions among the system’s networks change over time.  For example, the networks in a community of captive monkeys are based on behaviors such as mutual grooming, fighting, assisting in fights and displaying status signals such as teeth-baring. In the banking industry, the primary activities revolve around interbank lending, loan syndication, bond-issuing services and insurance.

In such systems, the lead into a crisis appears to be characterized by both the collapse of the keystone network and a decoupling of the other networks from the keystone network. Early detection of these patterns can be used to assess the tipping point, allowing us to predict and prevent such collapses from occurring.

“There may not much teeth-baring in the banking industry, however we did determine that interbank lending likely would be the network in that system that is of comparable importance to subordination signaling in monkey colony,” said McCowan.

She noted that these keystone networks are critically important because they significantly influence the stability of other relationships or networks within each respective system.

Admittedly, comparing rhesus macaques to a financial system is unconventional. However, the authors suggest that these research methods provide one approach that could be scaled up in order to model the vulnerabilities of the financial system as well as other human social systems. Such patterns of vulnerability are also likely to have significant implications for both individual and population health in both monkeys and humans, which the research group among other collaborators are currently investigating with R01 and R24 NIH support.

Funding for the study was provided by the National Science Foundation and the National Institutes of Health.


January 7, 2014  

Wildfires, Monkeys, And Understanding Overall Health: Long-term impact of air pollutants

During June and July 2008, almost 2,000 wildfires ignited in Northern California, leading to high levels of inhalable particulate matter (PM) in the Sacramento Valley that lasted for almost two weeks.  PM2.5 (the terminology for inhalable particles smaller than 2.5 microns) at the UC Davis campus were recorded at 50 to 60 micrograms per cubic meter. Some readings reached as high as nearly 80 micrograms per cubic meter, well over the federal standard of 35 micrograms per cubic meter. 

Numerous human studies have shown that when children are exposed to PM early in life, there is a persistent negative effect on lung function that is retained at maturity. The biologic mechanism of this effect, however, is not known. There is also no data available on the impact of air pollutant exposures on the functional status of immunity in human infants and school-age children.

Infancy may be associated with increased vulnerability to high levels of air pollution exposure because of the rapid lung and immune system development that occur during the early months of life. Several studies suggest that short-term exposure to wildfire emissions (over a few days) can worsen symptoms of asthma and other lung diseases, but no studies have investigated whether there are long-term health consequences to such exposures.

The California National Primate Research Center has a large population of rhesus monkeys that live in outdoor field corrals, where they, along with the local human population, were exposed to these elevated PM levels during the wildfires. The fires occurred near the end of the season when the monkey babies are typically born, and thus there were a significant number of animals in the colony that were between one and three months of age at the time of the fires.

To address these gaps in our understanding of the effects of air pollutant exposure during early life, Dr. Lisa Miller, the CNPRC Respiratory Diseases (RD) Unit Leader, led a research project entitled “Persistent Immune Effects of Wildfire PM Exposure During Childhood Development” funded by the California Air Resources Board. Also on the project were Drs. Ed Schelegle and Candice Clay (RD), and John Capitanio (Brain, Mind, and Behavior Unit). The primary objective of this study was to determine the early life impact of wildfire PM exposure on immune parameters that modulate responses to infectious disease, and contribute to lung function decline.

The investigators compared immune parameters in smoke exposed animals and in a group of animals born during the same months the following year during which there were no wildfires, by analyzing peripheral blood samples. Both groups of animals also completed a series of lung function tests. All animals were studied when they were three years of age (young adulthood), and the sample collection did not affect the long-term health of the animal. This offers the opportunity to periodically evaluate the cohort of exposed animals in a longitudinal fashion. Data collected from this research is also being used for related studies to evaluate additional parameters, such as cardiovascular function.

The results showed that the first three months of life appear to be a highly sensitive window of susceptibility, with lower levels of immune system parameters in smoke exposed animals compared to control animals, suggesting that these individuals are more susceptible to infectious diseases. Animals that had the most impaired immune response tended to also have reductions in several measures of lung function, particularly female animals.   These results suggest that infancy is a period during which high PM exposures may adversely influence development of a branch of the immune system and also adversely affect the development of lung function, leading to changes that persist into adulthood. 

Evaluation of this outdoor rhesus monkey colony has provided a unique opportunity to investigate the long-term impact of environmental emissions on overall health.  

The California National Primate Research Center is funded by the National Institutes of Health, Grant #OD011107.

Access the California Air Resources Board press release here.


December 12, 2013  

Tissue engineering research funded by CIRM

A UC Davis team, co-led by Alice Tarantal, PhD, and Peter Belafsky, MD, MPH, PhD, has received a $4.4 million grant from the California Institute for Regenerative Medicine (CIRM) for their project entitled “Tissue Engineered Recellularized Laryngotracheal Implants”, which proposes to develop a stem cell-derived airway transplant to cure a difficult, life-threatening problem known as severe airway stenosis.

With the funding of this disease team grant, Dr. Tarantal, CNPRC Reproductive Sciences and Regenerative Medicine Unit Leader and Professor of Pediatrics and Cell Biology and Human Anatomy; and Dr. Belafsky, Professor of Otolaryngology, will work to develop a safe and effective tissue engineered treatment for patients suffering from narrowing of the upper windpipe (trachea) and lower voicebox (larynx).

Severe airway stenosis is a life-threatening problem, which can result from head, neck, or throat cancers, as well as from trauma or rare physical conditions. According to Dr. Belafsky, it occurs in approximately 200 Californians each year and profoundly affects a person’s quality of life because it obstructs breathing and communication. Surgery, the current standard of care, can include use of tracheotomy tubes and stents, which are highly invasive, frequently providing less than satisfactory results, and can cause infection, pain, and voice loss.

Drs. Tarantal and Belafsky will be using a natural airway scaffold developed from a decellularized tracheal template with stem/progenitor cells from the patients themselves to create the tissue engineered implant. They hope to complete the necessary steps in order to conduct a Phase I clinical trial in the near future. The CIRM disease team grant enables the UC Davis team to first focus on an initial two years of preclinical and investigational new drug (IND)-enabling studies.
“There are a number of scientific questions that we plan to explore in the next few years,” said Dr. Tarantal, who also serves as Associate Director of the UC Davis Stem Cell Program. “We will develop and refine optimal transplantation techniques as well as determine the fate of implanted stem and progenitor cells for these implants. Firmly establishing safety and efficacy is critical to the goal of a transformative treatment for human patients.”

“The knowledge gained from these preclinical studies will provide us with a window into a new technology that could potentially be applied to other disorders in other organ systems,” said Dr. Belafsky, who also serves as Medical Director of the Voice and Swallowing Center at UC Davis. “Stem cell-derived, tissue engineering techniques could be extended to also treat children who suffer from severe laryngeal conditions that surgery cannot cure.”

“Stem cell-derived airway transplants or bioengineered stents also might be used for a vast array of airway diseases,” he adds. “The methods and technology developed in this research could also be used to treat disorders that require esophageal, bladder, or bowel replacement, where the current standards of care remain very limited and impair quality of life.”

This laryngotracheal reconstructions proposed are based on findings from European compassionate use exemptions in five dying patients, saving three of their lives. First-in-human studies were performed by University of London colleague and UK partner and collaborator, Dr. Martin Birchall. These compassionate use cases highlighted important gaps in knowledge and the critical need for preclinical studies in nonhuman primates to address questions of safety and long-term efficacy. Stem/progenitor cell-derived airway transplants that use the patients' own cells have the clinical advantage of not requiring anti-rejection medications.

To read the UC Davis Health System press release, go to: http://www.ucdmc.ucdavis.edu/publish/news/newsroom/8535


November 25, 2013  

Dr. John Capitanio named AAAS Fellow, adding to a list of honors

The American Association for the Advancement of Science (AAAS) has awarded the distinction of Fellow to John Capitanio, PhD, Core Scientist in the CNPRC BMB Unit.  Dr. Capitanio was given this honor for his distinguished contributions to understanding the causes and consequences of individual variation in temperament and personality in nonhuman primates, particularly in how behavior and social processes shape and constrain physiological processes as they relate to a number of significant health outcomes.

Dr. Capitanio continues to be recognized for his outstanding career and for making many important and significant contributions to a diversity of fields in primatology, psychology, and human health. His work has been highly interdisciplinary with expertise in a variety of areas including molecular biology, respiratory function, immunology, and neurobiology, among others.

This latest honor adds to Dr. Capitanio’s list of distinctions over the past two years. In June 2011, he was named a Fellow of the Association for Psychological Science for his sustained and outstanding contributions to psychological science in the areas of research, teaching, service, and application; and in June 2012, as an internationally recognized expert in the study of nonhuman primate psychobiology and health, he was selected as the American Society of Primatologists “Distinguished Primatologist for 2012”.

Dr. Capitanio manages his demanding research schedule and still finds time to be intensely involved with training the next generation of research scientists; he has collaborated with over 40 investigators, mentored 15 graduate students, taught countless classes in Psychology and Animal Behavior at UC Davis, and has received the UC Davis Outstanding Teaching Award.

AAAS is an international, non-profit organization with the goals of promoting cooperation among scientists, defending scientific freedom, encouraging scientific responsibility, and supporting scientific education and science outreach for the betterment of all humanity. It is the world's largest and most prestigious general scientific society, with more than 125,000 individual and institutional members, and is the publisher of the well-known and prestigious scientific journal Science.

Dr. Capitanio will be recognized with the rank of AAAS Fellow – a tradition begun in 1874 – on Saturday, 15 February, at the AAAS Fellows Forum during the 2014 AAAS Annual Meeting in Chicago.

UC Davis News and Information

November 8, 2013  

Vaccine fends off virus that strikes weak immune systems

An experimental vaccine modeling human cytomegalovirus (HCMV) infection — which can endanger developing fetuses, transplant recipients, patients co-infected with HIV and others who have a weakened immune system — proved safe and effective in research conducted at the CNPRC using the rhesus macaque model.

A team of scientists from the CNPRC, UC Davis Center for Comparative Medicine, and the University of Alabama, Birmingham, led by Peter Barry, PhD, CNPRC Infectious Diseases Core Scientist, developed the first-of-its-kind approach to preventing HCMV infection inducing broader immunological protection in rhesus monkeys. The publication describing the research is entitled: “Vaccination Against a Virally-Encoded Cytokine Significantly Restricts Viral Challenge”, November 2013, Journal of Virology.

Development of an HCMV vaccine has been ranked as the highest priority by the Institute of Medicine, an independent agency of the National Academy of Science, because of “the lives it would save and the disabilities it would prevent,” according to the U.S. Centers for Disease Control and Prevention.

“We’ve completed the first step in developing a vaccine to protect people against HCMV by interfering with the virus’s attempts to enter and infect cells in the body,” said Dr. Barry.

HCMV is a type of herpes virus that is spread through close contact with the saliva, urine or other body fluids of a person infected with the virus.

Most HCMV infections are not diagnosed because the virus typically causes few, if any, symptoms. As a result, most people infected are unaware that they harbor the virus — a condition that is of most concern among pregnant women, who are at risk for acquiring the virus from a close contact and subsequently transmitting the virus to her fetus.

Children who are congenitally infected may have cognitive and other developmental disabilities, including hearing loss and blindness. HCMV is the most common viral cause of congenital defects in the United States. About one in 150 children in the U.S. is born with congenital HCMV. About one of every five children with congenital HCMV infection — a total of 5,000 children each year — will develop hearing loss or developmental disabilities due to the infection, according to the Centers for Disease Control.

Because previous vaccine approaches failed to provide complete protection against HCMV infection, Dr. Barry and his collaborators adopted an “out-of-the-box” approach when designing the new vaccine. They focused on the virus’s ability to gain a lifelong foothold in the body, a stage of the virus’s life cycle that no other research lab has targeted in research on potential vaccines.

“HCMV is not like the influenza virus, which our immune systems can successfully clear from our bodies. HCMV infection is persistent,” Dr. Barry said. “Once you’re infected, you’re always infected.”

The virus’ persistence and ability to infect individuals without creating obvious symptoms of infection help explain why HCMV can be found in 50 to 80 percent of people under the age of 40.

The key to HCMV’s persistence, Dr. Barry and his colleagues theorized, is interleukin-10 (IL-10): the master regulator of the immune system, which works to rein in an over-zealous immune response to an invading pathogen.

Through his extensive research at the CNPRC, Dr. Barry previously discovered that early in its evolutionary history HCMV hijacked IL-10 and incorporated this gene into the virus’s own DNA code. As a result, HCMV can manipulate the body’s normal immune response to the virus.

In developing their vaccine strategy, the researchers focused on neutralizing HCMV’s own IL-10 so that the immune defense system was again capable of responding vigorously and effectively to the presence of the virus.

“We found that the monkeys did not become infected because, as a result of the vaccine, their immune systems generated neutralizing antibodies that prevented HCMV from entering and infecting connective tissue cells, epithelial cells and other major cell types that the virus targets,” Dr. Barry said.

“The vaccine also created ‘immunological memory,’ which enables the immune system to respond quickly and effectively whenever HCMV re-infection occurs.”

Dr. Barry has been focusing his research on HCMV using the rhesus macaque model his lab began developing over 25 years ago.  The work with the rhesus model, including the vaccine based on viral IL-10, could only have been possible here at UC Davis and the CNPRC.  “This research is an example of the critical importance of the monkey model, the preeminent position of UC Davis in research that has important clinical outcomes, and the demonstration of taxpayers’ money being used to improve the human condition” emphasizes Dr. Barry.  Long-term goals include advancing the results from the monkey studies into human clinical trials.


November 5, 2013  

Combination of adjuvant with influenza vaccine results in dramatic increase in protection of aged rhesus macaques

The flu season can be deadly for thousands of elderly people each year. There is a critical public health need to improve the effectiveness of influenza vaccines. Seminal research results were recently released by Drs. Chris Miller, DVM, PhD, CNPRC Core Scientist, and Tim Carroll, PhD, Post-doctoral scholar at the Center for Comparative Medicine, demonstrating the success of two inoculations of Colby Pharmaceutical Company’s JVRS-100 adjuvant in combination with the 2006-2007 seasonal influenza virus vaccine, Fluzone. (Colby announcement here). The combination generated enhanced immunity and provided superior protection in elderly rhesus macaques, and protected these immunized primates against challenge with live influenza virus.

A resulting manuscript, “The effectiveness of influenza vaccination of elderly rhesus macaques is dramatically improved by addition of a cationic lipid/DNA adjuvant”, has now been published with an accompanying editorial entitled, “Towards improved influenza vaccines,” in the October, 2013 Advanced Access edition of the Journal of Infectious Diseases (JID).  The editorial concludes that, “Overall, there is a great need to develop better influenza vaccines for the elderly and other vulnerable groups. The work described by Carroll et al provides another promising approach moving towards human efficacy trials.” 

The studies were coordinated by Colby Pharmaceutical Company’s VP Research, Jeff Fairman, PhD, in collaboration with Drs. Miller and Carroll.  Dr. Carroll works in Dr. Miller’s lab on eliciting broadly protective antibodies in the rhesus macaque model for human influenza.  He also recently presented additional studies at the CNPRC, entitled, “A whole inactivated H3N2 Influenza A virus vaccine adjuvanted with a cationic lipid/DNA complex (CLDC) protects rhesus macaques from heterosubtypic H1N1 Influenza A virus challenge.”

 “The data that was just published in JID clearly shows the remarkable enhancement of immunity from the JVRS-100 adjuvanted human influenza vaccine Fluzone, as measured by the antibody mediated anti-influenza immune responses. There was a dramatic decrease in virus infection in the JVRS-100 adjuvanted vaccine-inoculated macaques, and influenza viral replication was completely, or nearly completely, undetectable,” stated David B. Lewis MD, who is an immunologist at Stanford University and Chairman of the Colby Scientific Advisory Board.

It is remarkable that after a live flu virus challenge, only the JVRS-100 immunized monkeys had significantly lower levels of virus replication (p<0.01) relative to the control animals who were not immunized with JVRS-100. For example, peak levels of the flu virus were 100-fold lower in the respiratory tract secretions of elderly rhesus monkeys inoculated with Fluzone vaccine with the JVRS-100 added, as compared to the Fluzone vaccine alone monkeys.

Colby’s Chief Executive Officer, David Zarling, PhD, MBA, remarked that, “This newly published data from Colby’s recently completed NIH National Institute Allergy and Infectious Diseases (NIAID)-funded team is compelling and timely, and these well-controlled experiments clearly demonstrate that JVRS-100 adjuvanted flu vaccine is ready to go to the next level in clinical development.”

Other CNPRC scientists on this research project were Drs. Shannon Matzinger, Peter Barry, and Michael McChesney. Funding was provided by the National Institutes of Health, Public Health Service grants P51RR000169 (#OD011107) and U01AI074512.

August 8, 2013  

Formula-fed babies may be more susceptible to chronic disease

Formula-fed infants experience metabolic stress that could make them more susceptible than breast-fed infants to a wide range of health issues such as obesity, diabetes, liver problems and cardiovascular disease, according to new research conducted at the CNPRC by biochemists Carolyn Slupsky and Bo Lönnerdal, both of the UC Davis Department of Nutrition. The study sheds new light on the link between infant formula feeding and increased risk of chronic diseases later in life. The findings were reported in the June issue of the Journal of Proteome Research (2013 Jun 7;12(6):2833-45).

“We’re not saying formula-fed babies will grow up with health issues, but these results indicate that choice of infant feeding may hold future consequences,” said Slupsky, lead author of the study and also a faculty member in the UC Davis Department of Food Science and Technology.

Slupsky and her colleagues used nuclear magnetic resonance spectroscopy to look at how diet affects compounds in blood and urine in infant rhesus monkeys, which provide an animal model similar to humans in this type of research. After just four weeks, the formula-fed infants were larger than their breast-fed counterparts, had developed distinct bacterial communities in their gut, had higher insulin levels and were metabolizing amino acids differently.

“Our findings support the contention that infant feeding practice profoundly influences metabolism in developing infants and may be the link between early feeding and the development of metabolic disease later in life,” Slupsky said.

The formula-fed babies grew quickly — perhaps too quickly — which researchers link, in part, to excess protein.

“You want your baby to grow, of course, but growing too quickly is not such a good thing,” said Slupsky, who hopes her findings will help new mothers and the physicians who advise them make informed choices about what to feed their babies.

“Mother’s milk is an excellent source of nutrition that can’t be duplicated,” she said. For parents who formula-feed their infant, Slupsky hopes the science can lead to more beneficial formulas.

“Knowing what we now know, perhaps infant formulas that better mimic the protective effects of breast milk can be generated,” she said.

Slupsky and her team are now working to compare how compounds in breast milk differ between mothers and at different times during lactation, as well as how different formulas with varying nutrient content affect infant metabolism.

Collaborating with Slupsky and Lönnerdal on the study was Neill Haggarty of Fonterra Co-operative Group in New Zealand. Other authors were Aifric O’Sullivan, Xuan He and Elizabeth McNiven.

Funding for the study was provided by Fonterra Research and Development Centre in New Zealand.

UC Davis News and Information


August 1, 2013  

BPA Affects Lung Development

Collaborative efforts add critical information to understanding effects of BPA

BPA (bisphenol A), is used in the manufacturing of various plastics and food packaging, consumer products, some paper receipts, and medical devices. It is controversial because it exerts weak, but detectable, hormone-like properties which can mimic estrogen and may lead to far-ranging negative health effects including increased cardiovascular disease and diabetes in adults, increased cancer rates, including breast cancer, neurological difficulties, and hormonal and reproductive issues in both sexes and at all stages of life.

Recent results from research at the California National Primate Research Center (CNPRC) have shown that fetal BPA
exposure during a critical window of susceptibility in the third trimester, at levels similar to those measured in human blood, caused an increase in mucin genes and mucous cell maturation in the lungs (Environmental Health Perspectives, National Institutes of Health).

This is of environmental health importance because increases in airway mucins are hallmarks of a number of childhood lung diseases that may be impacted by BPA exposure. Overly abundant secretion and storage of mucous can cause airway obstruction as found in a number of lung diseases including asthma and bronchitis.

CNPRC scientists Drs. Laura S. Van Winkle, Respiratory Diseases Unit, and Catherine A. VandeVoort, Reproductive Sciences and Regenerative Medicine Unit, along with co-authors Drs. Shannon R. Murphy and Miriam V. Boetticher (UC Davis Center for Health and the Environment), conducted this collaborative study to investigate the effects of BPA on fetal development.

Their data indicate that exposure to environmentally relevant levels of BPA during fetal lung development can alter expression of secretory genes (Muc5B, Clara cell secretory protein (CCSP)) and proteins (Muc5B mucins and CCSP) in the conducting airways. They also found that this increase is most pronounced in the bronchi (proximal conducting airways).

In companion studies conducted at the CNPRC, it has been shown that exposure of pregnant monkeys to BPA disrupts development of fetal ovaries, potentially causing birth defects and reproductive problems that would not emerge for a generation (Link); and that BPA also affects several developmental parameters of the mammary gland of rhesus monkeys, including some that are relevant to breast cancer risk in humans (Link).

The study of BPA in a primate model is critical because the rhesus monkey has estrogen levels as well as reproductive and developmental processes that are similar to humans.

Dr. Van Winkle is a faculty member of the Department of Anatomy, Physiology and Cell Biology at the UC Davis School of Veterinary Medicine, and the UC Davis Center for Health and the Environment, as well as an Affiliate Scientist at the CNPRC .

Dr. VandeVoort is a faculty member of the Department of Obstetrics and Gynecology, UC Davis School of Medicine, in addition to being a Core Scientist at the CNPRC.

This research was funded by the National Institutes of Health.

July 9, 2013  

Maternal Antibodies Linked to Autism


In a major advance in understanding risk factors, and possible means of prevention of autism, Melissa Bauman, PhD, and David Amaral, PhD, performed studies at the CNPRC with rhesus monkeys to further define the role that maternal antibodies have to play in the risk of a child having autism. The research was published July 9, 2013 in Translational Psychiatry.

In 2008, Judy van de Water, PhD, from the UC Davis MIND Institute, discovered a group of autoantibodies—those that trigger immune responses against the body’s own molecules—that are especially common in mothers of children with autism. Dr. van de Water has found that this set of maternal antibodies could increase the risk of developmental problems in some cases of autism.

The CNPRC study explores the effects of the autism-specific IgG antibodies in a nonhuman primate model. Nonhuman primates live in complex social groups and use many forms of social communication. In addition, rhesus monkeys have a well-developed pre-frontal cortex, similar to humans, which other animal research models, such as rodents, lack.

Bauman, CNPRC research scientist, UC Davis assistant adjunct professor in the Department of Psychiatry and Behavioral Sciences, and a faculty member at the MIND Institute, and Amaral, CNPRC Core Scientist, Research Director of the MIND Institute, and senior author of the paper, exposed a group of pregnant female monkeys to IgG purified from human mothers of children with autism that exhibited fetal brain reactivity — the IgG-ASD group; a second group of pregnant female monkeys received IgG antibodies from the mothers of typically developing children. The third group included untreated animals that did not receive antibodies.

“The offspring of IgG-ASD antibody treated rhesus mothers consistently deviated from species-typical behavioral development of young rhesus monkeys,” Bauman said. The mothers of the IgG-ASD offspring were more protective towards their young during their first 6 months, compared to those that were injected with antibodies from women with neuro-typical children.

The mothers may have detected behavioral abnormalities in their IgG-ASD offspring that were so subtle that they escaped the researchers’ attention, Bauman said. “The heightened protectiveness of the monkey mothers was observed only when other animals were present, suggesting that the mothers perceived a greater risk to their IgG-ASD treated infants," she said.

Other alterations in behavior were observed as the animals matured. For example, the offspring of the IgG-ASD antibody-treated animals more frequently approached other infants in their rearing group. “Even more strikingly, as they grew older, the IgG-ASD offspring increased their approaches to unfamiliar peers,” she said. “Inappropriately approaching a novel animal is highly unusual and potentially dangerous for young rhesus monkeys.”

In addition to the behavioral changes, MRI analysis of the brains revealed altered patterns of neurodevelopment in the monkey offspring exposed to the IgG-ASD antibodies. The rate of brain growth was significantly faster in the male, but not female, IgG-ASD offspring, when compared with that of the control offspring. The total brain volume of the male IgG-ASD offspring also was significantly greater than normal, the researchers found.

While it is not clear why prenatal exposure to these antibodies only alters brain volume in the male offspring, a similar trajectory of abnormal brain development has been observed in male children with autism. Recent research from the MIND Institute has reported that boys with autism who were exposed prenatally to the same antibodies have significantly larger brains than boys with autism born to mothers without the IgG-ASD antibodies and typically developing control groups.

Amaral noted “that much research remains ahead of us to identify the mechanisms by which the antibodies affect brain development and behavior. But, this program of research is very exciting, because it opens pathways to potentially predicting and preventing some portion of future autism cases."


May 2013  

Clay receives competitive award to pursue research

Dr. Candice Clay, a post-doctoral fellow in the CNPRC Respiratory Diseases Unit, was awarded a two-year Hartwell Postdoctoral Fellowship, beginning in June 2013.

The Hartwell Foundation provides funding for postdoctoral training in biomedical science, and offers support to young scientists eager to pursue early-stage, innovative, and cutting-edge biomedical research that that has the potential to benefit children.

Research proposed in Dr. Clay’s Hartwell Biomedical Fellowship will help to identify mechanisms that limit pediatric defense against viruses and bacteria in the lung. Importantly, approaches to augment innate immune function of infant lungs may ultimately translate into improved therapeutics and vaccines for the highly susceptible pediatric population.

Dr. Clay’s application — including her research proposal, letters of recommendation, and curicula vitae — was chosen by the UC Davis Office of Research as an exemplification of the values of the Foundation, and selected to receive the two-year award.


PhD student Katie Chun selected out of 95 applicants

Brain, Mind, and Behavior  (BMB) doctoral student Katie Chun was one of only three students in the US and Canada who was honored with a 2012 Early Graduate Student Research Award from the American Psychological Association. She was chosen for demonstrating outstanding research abilities early in her graduate training, and showing a considerable level of independence in conducting her research.

Ms. Chun’s research focuses on the underlying physiological mechanisms of how personality may affect health outcomes (e.g., asthma) using rhesus monkeys. Specifically, she is interested in how behavioral inhibition is associated with differences in regulation of inflammation. One way that behavioral inhibition and inflammation may be related is through stress response systems, particularly the hypothalamic-pituitary-adrenal axis, which uses glucocorticoids as its main effector molecule. Normally, glucocorticoids regulate the immune system by decreasing inflammation. She is interested in how behavioral inhibition may be related to disruptions in this normal process, and how these effects could lead to alterations in health.

More than 95 graduate students applied for the award, representing basic, applied, and interdisciplinary science research areas within psychological science.

Ms. Chun is a third year graduate student in biological psychology at the University of California, Davis, where she works with Dr. John Capitanio, BMB Core Scientist. This award will help her to expand her past work and to better understand the molecular mechanisms of the association of behavioral inhibition and inflammation. For more information and to apply for this award, see: http://www.apa.org/about/awards/scistucoun-earlyre.aspx.


‘Rising Star’ in Psychology

Congratulations to Eliza Bliss-Moreau, Brain, Mind, and Behavior Unit, who was recently named one of the Association for Psychological Science’s (APS) “Rising Stars”. APS describes these young scientists as the “movers and shakers who are propelling science into new directions.”

Bliss-Moreau’s research focuses on the biological underpinnings of affect and emotion, with a particular focus on the mechanisms that generate individual differences.  “My core interest is to understand why there is such marked variety in people’s affective experiences — why some people love the taste of coffee and others hate it; why some people laugh at a joke while others scowl; why the same event can result in one person developing affect-related psychopathology yet leave another person relatively unscathed.” Read more about Bliss-Moreau and her research at: http://www.elizablissmoreau.com.

Dr. Bliss-Moreau was also one of two scholars awarded the 2013 UC Davis Excellence in Postdoctoral Research Awards, by the Office of Graduate Studies and the Graduate Council.  This award recognizes the vital role that Postdoctoral Scholars play in maintaining the reputation of excellent research at the University of California, Davis.


May 2013  

Tracking diet transitions during infancy from teeth


Similar to analyzing tree rings to understand the environment in which it grew, a careful look at the “rings” in primate teeth can tell the story of when an infant was exclusively milk fed, when supplemental food started, and at what age it was weaned. Professor of Human Evolutionary Biology at Harvard University and CNPRC Affiliate Scientist, Dr. Katie Hinde, was part of a research team to apply data from her studies on mother’s milk in rhesus monkeys at the CNPRC to a novel analysis technique of tooth material in monkeys, humans, and fossils (Harvard University press release).

Using the rhesus tooth crowns, the team was able to determine exact timing of birth, exclusive mother’s milk intake, and the weaning process, down to nearly the day. This validation of the analysis technique was then applied to human teeth and a Neanderthal tooth. The novel approach allows exciting insight into ancestral breastfeeding practices, as the team documents the first early life diet transitions in a juvenile Neanderthal, which shows a pattern of exclusive mother’s milk for seven months, followed by seven months of supplementation. This technique opens up extensive opportunities to investigate lactation in fossils and museum collections of primate teeth.

One of the most remarkable features of human development is that human infants are weaned much earlier than our closest ape relatives, often by several years. Although there is some variation among human cultures, this accelerated transition to foods other than mother’s milk is thought to have emerged in our ancestral history due, in part, to more cooperative infant care and access to a more nutritious diet. Shorter lactation periods can translate into shorter inter-birth intervals and higher reproductive rates. However, there is much debate about when accelerated weaning occurred in the hominin lineage. For the past few decades researchers have relied on tooth eruption age as a direct proxy for weaning age. Yet recent investigations of wild chimpanzees have revealed that first molar eruption occurs prior to the cessation of weaning, complicating the estimation of weaning from fossilized dentitions.

This study demonstrated that major dietary shifts during infancy are accurately recorded in mineralized dental tissues, which are apparent in fossil remains for thousands of years. An analysis of naturally shed baby teeth from human children with precise records of infant diet, and CNPRC macaques with known diet histories demonstrated that barium distributions reflect dietary transitions, beginning with the onset of breastfeeding and continuing through the weaning process. Barium levels in dental tissues formed during nursing are higher than in tissues that mineralize before birth, during solid food supplementation, or after nursing ceases.

After weaning, barium levels returned to baseline prenatal levels, suggesting an abrupt cessation of breastfeeding in Neanderthals at 1.2 years of age. Integration of information on the spatial distribution of elements such as barium and the precise daily record of tooth formation (Fig. 1) enables novel studies of the evolution of human life history, dietary patterns in wild primates, and human health investigations through accurate reconstructions and comparisons of breastfeeding history.

By applying these new techniques to primate teeth in museum collections, we can more precisely assess maternal investment across individuals within species, as well as life history evolution among species.

The research team was led by lead authors Drs. Christine Austin (Westmead Centre for Oral Health, Australia) and Tanya Smith (Harvard University Department of Human Evolutionary Biology), and senior author Dr. Manish Arora (Department of Preventative Medicine, Icahn School of Medicine at Mt. Senai). Dr. Hinde directs the Comparative Lactation Lab at Harvard University.

Austin C, Smith TM, Bradman A, Hinde K, Joannes-Boyau R, Bishop D, Hare DJ, Doble P, Eskenazi B, Arora M. Barium distributions in teeth reveal early life dietary transitions in primates. Nature (in press).

January 2013  

Unknown effects of long-term oxytocin use in children

Dr. Karen Bales, CNPRC Brain, Mind, and Behavior (BMB) Unit Leader, has done extensive research on the hormone oxytocin and its short and long-term effects on behavior in two monogamous species – prairie voles (Microtus ochrogaster) and titi monkeys (Callicebus cupreus). She is particularly interested in the role of neuropeptides such as oxytocin and vasopressin in social bonding and male parental care, as well as the effects of early experiences on the development of these behaviors.  Dr. Bales’ research has been in a wide range of publications, from an airline magazine for Valentine’s Day, to many online public interest stories, to countless peer-reviewed journals, including the current issue of Science (The Promise and Perils of Oxytocin, by Greg Miller, Science 18 January 2013: Vol. 339 no. 6117 pp. 267-269).  Her co-authors include Dr. Sally Mendoza, also a BMB Core Scientist, as well as Dr. Marjorie Solomon of the UC Davis MIND Institute, Dr. Suma Jacob of the University of Minnesota, UC Davis Psychology graduate students Allison Perkeybile and Olivia Conley, and UC Davis undergraduates Griffin Downing, Caleigh Guoynes, Meredith Lee, and Catherine Yun.  At the time of the research, Ms. Lee was a student at John F. Kennedy High School in Sacramento.

Author Greg Miller of Science, writes “Few substances produced by the human body have inspired as much hoopla as oxytocin. Although breathless media coverage often goes too far, it reflects a genuine and infectious excitement among many scientists about the hormone's role in social behavior: promoting trust and cooperation and making people more attuned to social cues. At first glance, oxytocin might seem like just what the doctor should be ordering. But as researchers have continued to explore the hormone's effect on human behavior, a darker side has emerged.”

Discussing the history of research with oxytocin, and addressing the question if the current jump to long-term human clinical trials with autistic children is premature, Miller includes Dr. Bales’ research and her concerns about giving children hormones whose effects have not been studied in the long-term. From her past research, Dr. Bales knows that even a single dose of oxytocin can have long-lasting effects; “The clearest message was that any exposure to oxytocin can cause long-term behavioral and neuroendocrine effects”.

“There’s been this quick leap from looking at a single dose of oxytocin in healthy adults to trying to give it to children with autism whose brains are still developing,” she says. Dr. Bales hasn’t found a single published study on the long-term behavioral effects of multiple doses of oxytocin in developing animals. “It seemed to me that we are really skipping a step.”

Recently Dr. Bales and colleagues tried to better mimic the type of oxytocin treatment now in clinical trials for autism, giving young prairie voles daily squirts of oxytocin in the nose for 3 weeks. In developmental terms, Bales says that the voles were roughly equivalent to 12- to 17-year-old children. In the short term, oxytocin made the voles more social, as expected. As adults, however, treated males had abnormal relationships with their partners. Several currently proposed clinical trials plan to administer oxytocin to children in this age group.

To Dr. Bales, her research findings raise the troubling possibility that repeated use of oxytocin nasal spray may cause long-term changes in the brain that negate or even reverse the hormone’s benefits, perhaps by tricking the brain into making less oxytocin of its own.

Out of frustration that science is moving too slowly, parents of autistic children have been willing to try experimental treatments, even before they’re fully vetted by researchers. At the same time, Dr. Bales hopes that science won’t let these families down again by rushing too quickly into clinical trials with a hormone whose effects aren’t adequately understood.

Dr. Bales’ research is funded by a grant from the National Institute of Child Health and Human Development (NICHD), which includes follow-up studies of chronic intranasal oxytocin administration in monkeys.


September 2012  

Plastics chemical shows two-generation effect in pregnant monkeys

Exposure of pregnant monkeys to the widely-used chemical bisphenol A (BPA) disrupts development of fetal ovaries, potentially causing birth defects and reproductive problems that would not emerge for a generation, according to research by Dr. Patricia Hunt and colleagues at Washington State University and Dr. Catherine VandeVoort at the CNPRC. The research was reported in a paper published this week (Sept. 24) in the journal Proceedings of the National Academy of Sciences.

(A news release from Washington State University can be found here.)

BPA is a chemical used in plastics, epoxy resins that line cans, and cash register receipts. Most people in the United States have measurable levels of BPA in their blood that indicate that exposure is nearly continuous. By using an animal with a reproductive system like that of humans, the research bolsters earlier work by Hunt and others documenting widespread reproductive effects in rodents.

What was done in this study?
Pregnant monkeys were given doses of BPA designed to produce a blood level of BPA similar to that found in humans. In this paper, the researchers looked at effects on the developing ovaries of female fetuses.This study has also provided samples to investigators working on other organ systems. A study on the mammary gland was led by researchers at Tufts and published in PNAS in May. Additional papers describing effects on other organs should be finished soon.

What were the findings?
When BPA was given in the second trimester of pregnancy, the fetal eggs had an increased incidence of chromosome damage. This damage could lead to miscarriage or birth defects in future offspring of the fetus. When given later in pregnancy, BPA disrupted the packaging of eggs into follicles. Follicles are the structures that eggs need to develop and grow properly.

“The effect of BPA on development of the ovary is especially concerning because the dose that is given to the pregnant female affects the fetus and if that fetus is female then the eggs that are being formed in the developing ovary are affected,” VandeVoort said. “The final results of the exposure may not been seen until the fetus grows up and has offspring of its own. If these same changes were happening in people, then the effects of BPA exposure in a pregnant woman might not been seen for 20 or 30 or more years, when her child reaches adulthood and has children of her own.”

“We are very concerned about the consequences of large numbers of eggs not forming proper follicles. All the eggs a female will ever have are formed before birth. The effect we have seen in this study could mean a shortened reproductive lifespan.”

Why use a monkey model?
Low doses of BPA have been shown to disrupt development in rodent models, but because mice naturally have low estrogen levels they may be more sensitive to BPA than humans. The study of BPA in a primate model is critical because the rhesus monkey has estrogen levels as well as reproductive and developmental processes that are similar to humans. The amount of BPA given to the monkeys in the study produced blood levels of BPA that are slightly lower than the mean level measured in humans in recent studies. Therefore, the results of this study are highly relevant to human health.

One of the major objectives of the CNPRC is to conduct primate studies in critical areas where rodent experiments are not sufficient. This study will help inform the public and regulatory agencies of the potential effects of BPA in humans.

“It’s important to do studies in a model with estrogen levels similar to those in women,” VandeVoort said. “Fetal development is very different in rodents and primates.”


June 2012

Capitanio named ‘Distinguished Primatologist’

An internationally recognized expert in the study of nonhuman primate psychobiology and health, Dr. John Capitanio, CNPRC Staff Scientist in the Brain, Mind, and Behavior (BMB) Unit at the California National Primate Research Center, was honored on Saturday June 23, with the distinction of being selected as the American Society of Primatologists (ASP) “Distinguished Primatologist for 2012”.

Capitanio was chosen to receive this prestigious national award for his outstanding career and for making a diversity of important and significant contributions to the field of primatology. His work has been highly interdisciplinary with expertise in a variety of areas (including molecular biology, respiratory function, immunology, and neurobiology, among others), with a specific focus on the role that temperament and personality play in social dynamics as they relate to a number of significant health outcomes.

In addition to the value of his work in basic science, Capitanio has also played an unusual role by conducting research that is important in applied arenas. Much of his research has contributed to improving the welfare of captive primates by discovering their needs for appropriate social housing, understanding and minimizing stress, identifying adverse environments for primates, and enhancing their health. Some of his biomedical research studies have focused on how individual-level characteristics affect physiological organization to influence disease-related outcomes.

Capitanio manages his demanding research schedule and still finds time to be intensely involved with training the next generation of primatologists; he has collaborated with over 40 investigators, mentored 15 graduate students, taught countless classes in Psychology and Animal Behavior at UC Davis, and has received the UC Davis Outstanding Teaching Award.

Showing tremendous service to the ASP over the past 25 years, Capitanio has led the Society as its President, served as a member or chair on nearly every committee (some of them concurrently), and since 1995 has managed the ASP website.

Capitanio became the third CNPRC primatologist in the history of the ASP to receive this important award (Dr. William Mason was the first recipient of the new award in 1989, followed by Dr. Andrew Hendrickx in 2002), more than any other institution.

Peter Judge, ASP Awards Committee Chairman, and Karen Bales (CNPRC BMB Unit Leader), current ASP President, presented Capitanio with a plaque, an honorarium, and an invitation to deliver the Distinguished Primatologist Address (Featured Speaker) at the next meeting of the Society, which will be held in Puerto Rico in 2013.


A sustained standing ovation greeted the news that Capitanio had won this important award. ASP members hold their awards ceremony at their annual banquet, which this year was at the beautiful Farm at Putah Creek, in Winters, California.


June 2012  

Immune cell populations studied that influence HIV disease outcome

A new study conducted at the California National Primate Research Center (CNPRC) may help clarify why some people infected with HIV are better able to control the virus. The results may also pinpoint a target for treatment during early HIV infection aimed at increasing the supply of certain immune cells in the gut, which the study shows could be an important factor in limiting HIV growth in cells throughout the body.

This new research looked at the balance between immune cell populations that might influence disease outcome. Published in the May 30, 2012 online issue of Science Translational Medicine ("SIV Replication in the Infected Rhesus Macaque Is Limited by the Size of the Preexisting TH17 Cell Compartment"), the study was authored by Principal Investigator Dennis Hartigan-O’Connor, MD, PhD, new staff scientist in the Infectious Diseases (ID) and Reproductive Sciences and Regenerative Medicine Units at the CNPRC; and Kristina Abel, PhD, Department of Microbiology & Immunology, University of North Carolina, (at the time of the study a faculty member at UC Davis and scientist at the CNPRC). The study was also conducted by Koen K. Van Rompay, PhD, DVM, ID Unit researcher. "The research involved a rhesus macaque model of HIV, monkeys who were infected with simian immunodeficiency virus, SIV" Abel said. "The course of SIV infection in these monkeys is quite similar to that of HIV in humans."

Both HIV and SIV infections cause severe CD4 T (immune) cell loss in the gut during early infection. As a result, the intestinal mucosal barrier, which is like the body's second skin or front line of defense against pathogens, is compromised. The "leaky gut" causes the normal gut bacteria flora to migrate out and activate the immune system throughout the body with disastrous health consequences. "The immune activation contributes to higher replication of the virus. And so the question is, why do some patients progress from infection to AIDS faster than others?" Abel asks.

Th17 cells, which are a subgroup of lymphocytes (white blood cells), are commonly found at mucosal surfaces and activate epithelial or outer layer barrier cells to secrete antimicrobial molecules, thus blocking disease-causing bacteria from entering. Abel points out that they also stimulate the production of "tight junction" proteins that keep all the cells that make up the intestinal barrier in close contact, "so that bacteria of the normal flora or their products cannot leak out."

The researchers wondered if there are more Th17 cells in the gut, would infection with the AIDS virus still have that early massive effect on gut permeability? And if you could keep the intestinal barrier intact during early infection with HIV, would it have an impact on the severity of disease progression, on having less severe disease in the long run?

Results of the study suggest that the answers may be yes. Rhesus macaques with higher numbers of Th17 cells in blood and intestinal tissue before they are infected with SIV subsequently have lower SIV viral loads. “Animals with more of these Th17 cells were better able to control SIV and this was due in part to macaques developing a more effective immune response by producing more SIV-specific CD4-positive T-cells to fight the infection. Our next step is to see if we can augment the Th17 effect, perhaps by looking at interleukin 17 (IL-17), the cytokine released by these cells, and testing to see if it has an effect,” said Hartigan-O’Connor.

“Further, if a treatment can be developed to increase Th17 cells in the gut, it may allow for a more effective immune response after exposure to an HIV vaccine or the virus itself,” he added.

Support for the research came from the National Institutes of Health, the Bill and Melinda Gates Foundation, the California National Primate Research Center, the National Center for Research Resources, the Harvey V. Berneking Living Trust, and the National Institute of Dental and Craniofacial Research.


May 2012  

BPA and Female Development

Adding important new findings to extensive scientific evidence that Bisphenol A (BPA) is a harmful substance, Dr. Catherine VandeVoort, staff scientist in Reproductive Sciences and Regenerative Medicine at the CNPRC, has been part of a team effort investigating the effects of BPA on the fetal development in nonhuman primates and the first paper, focusing on the fetal mammary gland, is now being published. (Tharp AP, et al. Bisphenol A alters the development of the rhesus monkey mammary gland. Proceedings of the National Academy of Sciences, 2012).

BPA, used in the manufacturing of various plastics and resins for food packaging, consumer products, some cash register receipts, and medical devices, is controversial because it exerts weak, but detectable, hormone-like properties which can mimic estrogen and may lead to far-ranging negative health effects including increased cardiovascular disease and diabetes in adults, increased cancer rates, including breast cancer, neurological difficulties, and hormonal and reproductive issues in both sexes and at all stages of life. A 2011 study demonstrated just how pervasive the chemical is – analyzing the number of chemicals pregnant women are exposed to in the U.S. found BPA in 96% of women.

The aim of the overall study, conducted at the CNPRC, was to determine whether maternal circulating levels of unconjugated BPA, similar to those found in human serum, affected the development of female rhesus monkey offspring. Rhesus monkeys pregnant with female fetuses were daily fed a small piece of fruit containing BPA during the late third trimester that resulted in serum levels of unconjugated BPA similar to those observed in humans, making the results of this study relevant to human exposure and health issues. Many tissues from the fetuses were sent to experts around the country – in the case of the mammary gland, to Dr. Ana Soto at Tufts University.

A quantitative analysis that compared the morphology of exposed and unexposed female neonatal mammary glands was conducted, and demonstrated that gestational exposure to BPA affected the nonhuman primate mammary gland development in ways similar to rodent results. Previous rodent studies had shown significant alterations in the gland’s morphology that varied from subtle ones observed during the exposure period to precancerous and cancerous lesions manifested in adulthood.

From what is known about the role of endogenous hormones in the development of the mammary gland it was also concluded that BPA affects several developmental parameters of the mammary gland of rhesus monkeys, including some that are relevant to breast cancer risk in humans.

"We think that our results suggest that it is very likely that fetal exposure to BPA would also increase the propensity to develop mammary cancer in monkeys," Soto said.

The sum of all the findings "strongly suggest that BPA is a breast carcinogen in humans and human exposure to BPA should be curtailed," she said.

This study took advantage of an ongoing research project by Dr. VandeVoort that was designed to assess the effect of BPA on ovarian morphogenesis and to determine the circulating levels of unconjugated BPA in orally exposed female rhesus monkeys. Other tissues are also being analyzed for possible affects of BPA, including lung development.

WASHINGTON Food-packaging chemical could lead to breast cancer, study finds. By Renee Schoof, McClatchy Newspapers


March 2012  

New Discoveries Lead Towards Better Understanding of Battle Between HIV and the Immune System

The GI tract is considered a major 'battlefield' between the immune system and HIV. The intestinal mucosa is the site of early infection and aggressive transmission for HIV, making it the first line of defense against the infection. A better understanding of what happens in the GI tract may lead to knowledge of how to eradicate the HIV virus, new treatment options, and strategies for vaccine development.

A recent study by Dr. Chris Miller, CNPRC Infectious Diseases Unit, and Dr. Barbara Shacklett, UC Davis Department of Medical Microbiology and Immunology, used the monkey model of HIV, simian immunodeficiency virus (SIV), to determine if the ability of primary myeloid dendritic cells (mDCs) to promote the production of regulatory T cells (which modulate immune-system attacks) is affected by chronic SIV infection.

Results found that GI tissue in monkeys infected with SIV can ramp up production of regulatory T cells (Treg), weakening the body's attack against the invading virus. Tissue mDCs from SIV- infected animals exhibited an enhanced capability to induce Treg and may contribute to the accumulation of Treg in lymphoid tissues during progressive infection. The activation status of dendritic cells impacts this process but the capacity to induce Treg was not restricted to mucosal dendritic cells in infected animals. The discovery could help explain how HIV evades the body's immune defenses, and lead to a treatment strategy that could slow the production of this restraining type of T cell. This would let the immune system go after the virus more aggressively.

Sept 2011  

Obama Names Valeggia PECASE Award Winner
Conducted her PhD research at CNPRC

On September 26, 2011, President Barack Obama named Dr. Claudia R. Valeggia, who conducted her PhD research at the CNPRC, as one of 94 recipients of the Presidential Early Career Awards for Scientists and Engineers (PECASE), the highest honor bestowed by the United States government on science and engineering professionals in the early stages of their independent research careers.

“I was speechless,” Valeggia said upon finding out the news, now Professor in the Department of Anthropology at the University of Pennsylvania. “It’s such a great honor, and it’s such a big push for my research.”

Annually, the most meritorious scientists and engineers whose early accomplishments show the greatest promise for assuring America’s preeminence in science and engineering are selected for their pursuit of innovative research at the frontiers of science and technology, and their commitment to community service as demonstrated through scientific leadership, public education, or community outreach.

Valeggia was chosen as a PECASE recipient for her work on somatic, developmental, cultural and endocrine correlates of key life history transitions, and for developing educational programs for indigenous people, promoting student training, and aiding hospitals to help determine infant feeding choices.

Originally from Argentina, Valeggia came to UC Davis in pursuit of a PhD, receiving a MS (1995) and then a PhD in Animal Behavior (1996). At the CNPRC, under the direction of Dr. Sally Mendoza, CNPRC Staff Scientist in the Brain, Mind, and Behavior Unit, she investigated female reproductive biology, and the effects of pair-bond and social context on male-female interactions in titi monkeys (Callicebus moloch).


Male titi monkey and infant daughter at CNPRC.

Being an “excellent bench scientist”, Mendoza notes that Valeggia’s novel endocrine and immune assay techniques that she developed with nonhuman primates at the CNPRC continue to contribute to the current work on characterizing the neurobiology of the pair bond in titi monkeys. An excellent example of translational research, Valeggia has been applying these techniques to her research on reproductive transitions in human populations.

Reflecting on Valeggia’s time at the CNPRC, Mendoza states “I am proud of the accomplishments of all of my students, but Claudia is one of the best students I have had the opportunity of mentoring and I am in awe of the importance of the work she is doing for the women populating her study groups in the US, Central and South America.”

Advancing to Harvard University as a postdoctoral researcher, and then in 2005 to the University of Pennsylvania, Valeggia’s research focuses on the interactions between human reproductive biology and the ecological and cultural context in which it develops. Taking a biocultural approach, she concentrates on how the interplay between biology and culture takes a central role in interpreting reproductive patterns. Valeggia’s work with indigenous populations in Argentina and Guatemala, and with women in the US, has added an exciting interdisciplinary component to her research program that provides insights into reproductive processes in culturally changing populations.

Mindful of the importance of her research not only for the scientific communities, but also for the people she studies, Valeggia publishes in Spanish, as well as English, to make her work accessible to the local people and health organizations. She has joined forces with health agencies to facilitate delivery of information and health care, and takes care to maintain the highest scientific standards while at the same time making her work immediately useful.

“I have not met anyone that is familiar with Claudia’s work that is not impressed with its importance, quality, and clarity, and her scientific diversity.“ states Mendoza.

Valeggia's research at the CNPRC was supported by funds from the National Institutes of Health (NIH). The CNPRC is supported by a grant from the National Center for Research Resources, a division of NIH.

July 2011  

New Research Project Tests Cure for HIV

CNPRC researchers are taking part in a consortium lead by the University of North Carolina at Chapel Hill that aims to find ways to eradicate HIV, the virus that causes AIDS, from the body.

Antiretroviral drugs allow people infected with HIV to control virus levels and maintain relatively good health, but with current treatments the virus is never fully eliminated from the body. This research study will aid in understanding where and how HIV survives in the body and how it might be eliminated, laying the basis for designing clinical trials of these novel therapies in individuals infected with HIV.

CNPRC scientists Paul Luciw, professor at the Center for Comparative Medicine and the Department of Medical Pathology, and Koen van Rompay, research scientist at the CNPRC, will carry out testing of novel therapies in rhesus monkeys experimentally infected with simian immunodeficiency virus (SIV), which is genetically similar to HIV.

The consortium is named the Martin Delaney Collaboratory after Martin Delaney, an internationally recognized AIDS activist who died in 2009. The partners will undertake more than a dozen research projects to discover how the virus can remain dormant and virtually invisible, identify drugs and treatments capable of ridding the body of persistent infection and test these new strategies in animal models so that they can be translated into people.

The other universities taking part are: Case Western Reserve University; Johns Hopkins University; UCLA; UC San Diego; UC San Francisco; The Gladstone Institute; University of Minnesota, and the University of Utah. Scientists at Merck Research Laboratories are also collaborating.

July 2011  

Tenofovir Component of Successful Prophylaxis for HIV Prevention

Tenofovir (Viread), an antiretroviral HIV drug first shown by the CNPRC to be safe and effective in treating monkeys that were infected with SIV (Simian Immunodeficiency Virus), has once again been used as the key ingredient in a pair of successful HIV preventative studies. The two new studies, by the Bill & Melinda Gates Foundation and the U.S. Centers for Disease Control and Prevention, found that daily pills formulated with tenofovir lowered the risk of HIV infection by up to 73% when given to uninfected heterosexual men and women in Africa who have an HIV-infected partner. This brings new hope for someday offering a medical shield against HIV infection.

Press Release: http://www.nytimes.com/2011/07/14/health/research/14aids.html
Research Rationale: http://www.cdc.gov/hiv/prep/resources/qa/index.htm

June 2011  

Capitanio Honored as Fellow of APS

For his sustained and outstanding distinguished contributions to psychological science, Dr. John Capitanio was made a Fellow of the Association for Psychological Science (APS) in June 2011 – “A total surprise and very nice honor”. Fellow status is awarded to APS Members after a minimum of 10 years of postdoctoral work who have made sustained outstanding contributions to the science of psychology in the areas of research, teaching, service, and/or application.

January 2011  

Dallas Hyde Honored as Fellow of the American Association of Anatomists

CNPRC Director Dr. Dallas Hyde has been distinguished in being named a Fellow of the American Association of Anatomists (AAA).  The rank of Fellow is designed to honor notable members who have demonstrated excellence in science and in their overall contributions to the anatomical sciences. 

The AAA was founded in Washington, D.C. in 1888, for the "advancement of anatomical science." Today, AAA is the professional home for an international community of biomedical researchers and educators focusing on anatomical form and function.  Dr. Hyde has served on the Program Committee and is an Associate Editor of Anatomical Record for the AAA.

Dr. Hyde's research at the CNPRC is focused on airways epithelial and inflammatory/immune cell interaction, which is important in maintaining the ability to combat infectious disease and remove and/or repair injured cells in the lungs. Lung growth, differentiation and aging, particularly under the perturbation of inhaled allergens and pollutants are other important research interests. His laboratory studies asthma, pulmonary fibrosis and emphysema in nonhuman primates as models for investigation into understanding human disease.

Joining the UC Davis School of Veterinary Medicine faculty in 1979, Dr. Hyde is a member of the Department of Anatomy, Physiology and Cell Biology, and served as chair from 1988 to 1998. He has also served as the School of Veterinary Medicine Associate Dean for Research and Graduate Education from 1997 to 2002, and in 2000 was appointed Director of the California National Primate Research Center.

Dr. Hyde will be recognized at the AAA Annual Meetings Awards Banquet on Tuesday, April 12, 2011 in Washington, D.C., at the Convention in Experimental Biology.


November 2010  

Spinal Cord Research Shows Natural Recovery
Enhancing innate system has potential for better treatment options

Spinal cord research is being conducted with rhesus monkeys at the CNPRC, under the direction of Dr. Mark Tuszynski, Department of Neurosciences at the University of California, San Diego School of Medicine.

Tuszynski and Lead Researcher Dr. Ephron Rosenzweig, UC San Diego Department of Neurosciences, have just released research results from monkey studies that show undamaged neurons spontaneously stepping-in to fill the gap left by severed nerves after a minor spinal cord injury.  Up to 60 percent of the connections were restored within 24 weeks after injury.

The results were published Nov. 14 in the journal Nature Neuroscience.

Rosenzweig noted his surprise with the results, considering that this phenomenon has not been seen in the rat – the traditional research model for spinal injuries.

The work highlights an important role for primate models in translating basic scientific research into practical, therapeutic treatments for people. The spinal cords of humans and other primates are different from rodents, both in overall anatomy and in specific functions.  (Read more about the ethics of using primates in research).

Tuszynski’s team is continuing studies on how the nervous system is able to generate so much natural growth after injury. Since rhesus monkeys’ spinal cords and nervous system closely resemble that of humans, this research, and uncovering the mechanism by which the neurons re-grow, could lead to improved drug or gene treatment options in people with spinal cord injuries.

UC San Diego announced the research findings November 16, 2010.

October 2010  

2009 Illness Shown to be New Adenovirus in Titi Monkey Colony

UC Davis veterinary and human health experts today (Oct. 26) provided perspective on a newly identified virus that sickened monkeys and may have infected an employee at the campus’s California National Primate Research Center last year.

July 2010  

Successful HIV Protection

The 2010 XVIII International AIDS Conference in Vienna, Austria, was buzzing with excitement Monday, July 19th, with the announcement of successful trial results for the newly tested vaginal microbicide gel Caprisa, a recent addition to the arsenal in the fight against HIV infection in women. The Phase 2 clinical trial tested the safety and effectiveness of the gel among nearly 900 women at two sites in South Africa.

The success of Caprisa is believed to be due to the addition of the anti-retroviral drug tenofovir. Research by Dr. Koen Van Rompay at the CNPRC during the 1990s was the first to demonstrate that tenofovir (PMPA) was effective in treating animals that were infected with SIV (Simian Immunodeficiency Virus), laying the groundwork that led to human clinical trials. Also at the primate center, Dr. Chris Miller tested a tenofovir gel as a vaginal microbicide in the late 90s in the monkey model and found it to be effective. Tenofovir is now the most widely used anti-HIV drug in the world, with use in over 100 countries worldwide.

The proof of concept trials with Caprisa had an efficacy rate of 39% overall; however women who adhered strictly to the gel instructions had a 54% efficacy rate.

Another ongoing trial called VOICE (funded by the U.S. National Institutes of Health), involves a daily-used tenofovir gel. Newly begun in the Fall of 2009, this study will enroll nearly 5,000 women in four African countries.

Some are calling this a historic day in the fight against HIV. Van Rompay notes how important animal research was to the early development of HIV prophylaxis regimes, and how important it continues to be as scientists develop new and more effective treatments.

April 2010  

First Annual Lung Research Day Symposium
The 1st Annual Lung Research Day Symposium was held on April 14th, 2010 at the Genome and Biomedical Sciences Facility on the UC Davis campus.  Over 110 participants representing UC Davis, industry, and government agencies spent a dynamic day attending seminars, discussing poster presentations, and networking with colleagues. This symposium celebrated the collaborative research efforts and multidisciplinary approach that have long been recognized at UC Davis for research in basic lung biology and pulmonary medicine.  Symposia session topics were focused on nonhuman primate models of lung disease, translational research projects, imaging and instrumentation approaches, and new findings in airway epithelial cell biology.

CNPRC Respiratory Diseases (RD) Unit Staff Scientists were an integral part of the day’s events, including Director Dallas Hyde, RD Unit Leader Lisa Miller, Edward Schelegle, and Kent Pinkerton.  Also participating were RD Unit Affiliate Scientists Mark Avdalovic, Mike Evans, Laura Van Winkle, and Reen Wu.

The event was co-hosted by the UC Davis Health System Clinical and Translational Science Center; the UC Davis School of Medicine, Veterinary Medicine and College of Engineering; and the California National Primate Research Center.

April 2010  

UC Davis Academic Federation and Academic Senate Awards for Excellence

Dr. Koen Van Rompay, Infectious Diseases Unit CNPRC, was honored in April as a recipient of the 2010 Academic Federation Award for Excellence in Research, recognizing his outstanding research efforts and professional accomplishments in the field of HIV/AIDS. Along with the professional recognition for his dedication to furthering our understanding of the biology, prevention and treatment of HIV/AIDS, Van Rompay will also receive a monetary award — “the $500 that I'll receive goes straight towards the kids of the Mother Teresa School in India”, one of the many groups that Van Rompay supports through his nonprofit organization, Sahaya International.

Van Rompay notes “My research accomplishments are only possible thanks to everyone's dedication here at the primate center…. I consider the award more for the whole primate center than just myself”.

Recognized by the Academic Senate with a 2010 Distinguished Teaching Award for Graduate/Professional Teaching was Dr. Lynne Isbell, UC Davis Professor of Anthropology and Animal Behavior. Isbell is regularly at the CNPRC, using the outdoor-housed rhesus macaque colonies to further her understanding of primate behavior and also to introduce her students to field research methods.

UC Davis Community Service Award Recognizes Van Rompay

Koen Van Rompay has also been honored by UC Davis in being named a 2010 Community Service Award (CSA) winner in the highest “Outstanding” category. Dr. Van Rompay was one of six awardees in this top category out of 204 that were recognized (Outstanding, Gold, Silver, Bronze, and Honorable Mention). In addition, UC Davis earned a place on the President's Higher Education Community Service Honor Roll, a national honor recognizing the university's common interest in serving the community. (“Campus honored by President Obama for community service”, California Aggie, April 29, 2010). The UC Davis CSA recognizes the dedication to community service by hundreds of UC Davis students, staff, and faculty each year. Van Rompay earned this distinction, along with his UCD Student Club, for his tremendous accomplishments with his nonprofit group Sahaya International (sahaya.org), founded in 1999 to make a difference in the lives of children in developing countries, especially those that are affected by the HIV / AIDS epidemic. Van Rompay has inspired hundreds of people at UC Davis and in the Davis community to become involved with his mission to provide an education and healthy life for these children. The six Outstanding Awardees will be invited to a small reception with Provost Enrique Lavernia on May 12th.
March 2010  

Study finds link between mother’s milk and infant behavior

The quality and quantity of rhesus monkey breast milk has been found to send a signal to nursing infants, influencing the infant’s behavior and temperament.  Drs. Katie Hinde and John Capitanio of the CNPRC, in collaboration with the Smithsonian Institution, recently published the results of this landmark research done at the primate center on the outdoor-housed Rhesus macaques. "Our results suggest that the milk energy available soon after birth may be a nutritional cue that calibrates the infant's behavior to environmental or maternal conditions", says lead author Katie Hinde.

The study found that milk from mothers who weighed more and had had previous pregnancies contained higher available energy when their infants were one month of age. Lighter, less experienced mothers produced milk with lower available energy.

The CNPRC and the Smithsonian’s National Zoological Park used this natural variation in breast milk quality and quantity to present evidence that a mother’s milk sends a reliable signal to very young infants about their environment. This signal may program the infant’s behavior and temperament according to expectations of available resources and discourages temperaments that may prove risky when food is scarce.

Davis Enterprise: Thursday, April 1, 2010, "UC Davis study: Mom's milk affects monkey behavior"

September 2009   The 25-year history of contributions to HIV/AIDS research and discovery by California researchers was celebrated at a September 25th event hosted by the CCM.

Keynote speaker was 2008 Nobel Laureate Dr. Françoise Barré-Sinoussi, co-discoverer of HIV. The event celebrated the teamwork and contributions of researchers from California, including researchers from the CNPRC who contributed early on in the AIDS epidemic, and who continue to contribute to the advancement of the science, treatment and prevention of HIV/AIDS.

Davis Enterprise: Wednesday, September 30, 2009, "HIV Teamwork was Key"

May 2009   CNPRC Director featured in KVIE TV documentary on Asthma

Dr. Dallas Hyde appeared as an expert guest on the television documentary "Breathless! Asthma in the Valley" which first previewed in May 2009 on KVIE television. The documentary can be viewed online at: http://www.kvie.org/programs/kvie/viewfinder/breathless/default.htm.

January 2009   Two UC Davis scientists receive state funding for innovative stem cell research

Excerpt from: UC Davis Newsroom

Two UC Davis School of Medicine stem cell researchers were among the nearly two dozen scientists who received research funding this week from the California Institute for Regenerative Medicine (CIRM), the state's stem cell agency.

Alice Tarantal, professor of pediatrics and director of the Center of Excellence in Translational Human Stem Cell Research was awarded grant funds that support work that creates new techniques and capabilities for stem cell research. Tarantal's project is looking at new ways to utilize in vivo imaging technology currently used in clinical settings for stem cell research.

January 2009   Findings from University of California, California National Primate Research Center in gene therapy reported

Excerpt from: Gene Therapy Weekly, January 22, 2009

Researchers detail 'A heterologous DNA prime/protein boost immunization strategy for rhesus cytomegalovirus' new data in gene therapy. According to recent research published in the journal Vaccine, "A previous study in nonhuman primates demonstrated that genetic immunization against the rhesus cytomegalovirus phosphoprotein 65-2 (pp65-2) and glycoprotein B (gB) antigens both stimulated antigen-specific antibodies and CD8 T cell responses, and significantly reduced plasma viral loads following intravenous challenge with RhCMV. It was also noted in this study that weak CD4 T cell and neutralizing antibody responses were generated by DNA alone."
December 2008   PET/MRI COMBO IS #6 on Top Innovations List

Excerpt from: http://www.the-scientist. com/2008/12/1/45/1/

Simon Cherry and colleagues in the Department of Biomedical Engineering have been working for several years on PET scanners for small animals that could be used in laboratory research. One such machine is already in use at the California National Primate Research Center at UC Davis. This technology has the potential to reduce the numbers of animals used in research, which supports the Three R’s of Animal Use in Research: reduction, refinement, and replacement.

Proc Natl Acad Sci 105:3705-10, 2008; Nat Med 14:459-65. 2008
September 2008   Research by Dr. Golub at the CNPRC has shown that iron deficiencies in infants can lead to later behavioral problems similar to ADHD in humans, an delayed effect that had been overlooked in studies with human children.

Abstract from Wiley Interscience, 22 Sept 2008

Iron deficiency anemia and affective response in rhesus monkey infants

Mari S. Golub 1 *, Casey E. Hogrefe 2, Keith F. Widaman 3, John P. Capitanio 2,3

Infant iron deficiency anemia (IDA) occurs spontaneously in monkey populations as it does in humans, providing a model for understanding effects on brain and behavior. A set of 34 monkey infants identified as IDA (hemoglobin <11 g/dl) over a 5-year period at the California National Primate Research Center (CNPRC) was compared to a set of 57 controls (hemoglobin >12 g/dl) matched for age and caging location. The infants had participated in a Biobehavioral Assessment conducted at 3-4 months of age at CNPRC that included measures of behavioral and adrenocortical response to a novel environment. IDA males differed from control males in two factors (activity, emotionality) derived from observational data taken on the first and second day of the exposure to the novel environment. In the male infants, IDA was associated with less restriction of activity in the novel environment on both days and less emotionality on the second day (p < .05). IDA males also displayed less response to approach by a human (human intruder test) than did control males. IDA females did not differ from controls. Adrenocortical response was not significantly affected. These findings may be relevant to functional deficits in human infants with IDA that influence later behavior.

© 2008 Wiley Periodicals, Inc. Dev. Psychobiol 51: 47-59, 2009

Protecting Researchers from Animal Rights Activists Governor Schwarzenegger Signs AB 2296

Dr. Dallas Hyde, Director of the California National Primate Research Center testified on behalf of AB2296 during the legislative hearings. His expertise and personal experiences of harassment clearly illustrated the severity of what researchers encounter while trying to fulfill their academic mission.
August 2008   Mr. Holder spoke at the CNPRC in the morning of August 8, 2008, and in the afternoon with a local radio station

Pro-research activist Tom Holder, to speak on campus

Excerpt from: http://blogs.ucdavis.edu/egghead/2008/08/05

Tom Holder, who helped found a student organization at Oxford University, England to counter animal rights protests, will give a talk at the California National Primate Research Center at noon on Friday, Aug. 8.

The Oxford group, "Pro-Test" organized in response to a mounting campaign of violence and intimidation against scientists by animal rights extremists. As a result, the university was able to complete work on a new biomedical sciences research laboratory.

Holder recently moved to the U.S. and has started a new organization, Speaking of Research. He is currently touring California talking to various groups. His visit could not be more timely, given the escalating series of incidents at UC campuses in recent months, culminating in Saturday’s fire bombings at the homes of UC Santa Cruz researchers.
July 2008   ADHD study puts money where the brain is: MIND Institute uses prizes to get - and measure - subjects' attention

By Sam McManis

Excerpt fromthe Sacramento Bee: Sunday, Dec. 14, 2008 - 12:00 am | Page 5L

You know the type. Heck, you may even be the type. You flit from task to uncompleted task, losing interest based on how hard and boring it becomes. You choose the task of least resistance and focus on immediate gains, not richer, more long-term rewards.

So who are you?

"Around tax time," says UC Davis MIND Institute researcher Julie Schweitzer, "that's everybody. That's when cleaning the toilet suddenly becomes really interesting."

But for people with ADHD – attention deficit hyperactivity disorder – such distractedness is not mere procrastination. Though the hyperactive aspects of the condition are most obvious, inattention arguably can be more debilitating – especially for adults.

Schweitzer, an associate professor in UC Davis' department of psychiatry and behavioral sciences, is spearheading a study to determine what chemical functions in the brain trigger an ADHD person's compulsion to abandon tasks and exhibit "exploratory" behavior.

The study is zeroing in on a neurohormone called norepinephrine, which affects the part of the brain (the locus coreruleus) where attention is controlled. If the study backs Schweitzer's hypothesis – that if the norepinephrine can be regulated pharmacologically or behaviorally, it could help keep people on task – it could have significant implications in ADHD treatment.

Norepinephrine is far less known and less studied than dopamine, its fellow ADHD-intensive chemical. Firing rates for norepinephrine could explain why you ditch paying the bills halfway through to floss your teeth or rearrange your sock drawer.

The link between decision-making and neurochemistry is not entirely new, Schweitzer concedes, but it's been almost entirely focused on dopamine, the so-called "pleasure" hormone.

Studies centering on norepinephrine and task-to-reward difficulty have been conducted only on primates. And one such study on monkeys determined that measurement of pupil size of subjects can determine norepinephrine levels, meaning costly and invasive brain imaging is not needed.

Schweitzer sees norepinephrine uptake inhibitors working in tandem with existing ADHD medications that regulate dopamine levels. In May, the Food and Drug Administration approved a new drug for ADHD use, Strattera, which affects only norepinephrine levels.

"Potentially," Schweitzer says, "I think you will subtype the kinds of ADHD in children and adults according to the norepinephrine bursts vs. the dopamine. Then we'd have a better idea about the intervention that is most appropriate."

Commentary: Personality and Disease

Excerpt from July 15, 2008


For the full text see: Brain, Behavior, and Immunity Volume 22, Issue 5, July 2008, Pages 647-650 Personality and Disease

John Capitanio is a Research Psychologist at UC Davis and Associate Director of the California National Primate Research Center. He was guest-editor of the special issue of the journal Brain, Behavior and Immunity on "Personality and Disease," published in July 2008.

For centuries, people have thought that particular personality characteristics may be associated with an increased likelihood of illness. New research, described in a special issue of the journal Brain, Behavior, and Immunity, suggests some immunological links between personality and disease.

One study in this issue, reported by Anna Marsland at the University of Pittsburgh, shows that healthy, middle-aged, people who tend to be verbally and physically aggressive show higher levels of cytokines that promote inflammation — an immune process that has been linked to a variety of serious diseases, such as cardiovascular disease, cancer, arthritis, Alzheimer’s disease, and even depression — compared to less antagonistic individuals. This effect was found even after controlling for the fact that antagonistic individuals also often practice poor health behaviors, such as smoking, alcohol use, and so on.

People with different personalities may be "built" differently.

Marsland’s results suggest the intriguing possibility that individuals with different personality characteristics are "built" differently. A separate study reported in this issue, by Erica Sloan at the University of California, Los Angeles, supports this idea.

Rhesus monkeys, like humans, show a personality characteristic that reflects their interest in friendly interaction with others. In monkeys this trait is called Sociability, which is similar to Extraversion in humans. Sloan studied the lymph nodes of monkeys that were high or low in Sociability. Lymph nodes are small organs scattered throughout the body, and are the places where the immune system fights infections. Lymph nodes also contain nerve fibers from the sympathetic nervous system, and Sloan found that animals that are low in Sociability had a higher density of nerve fibers than did animals that were high in Sociability. Nerve fibers release norepinephrine when individual are stressed, and norepinephrine generally suppresses the immune response to viral infections. This finding of a relationship between a personality characteristic and neural innervation of lymph nodes may help explain the well-known result that humans that are socially isolated and introverted typically have a higher risk of immune-mediated diseases, such as upper respiratory infections, allergy, and SIV/HIV infection. Together, the data presented in this special issue support the idea proposed recently by the former Director of NIH that, in the future, the most effective treatments may be those that are "personalized" based upon an individual’s genetic and behavioral characteristics.
May 2008   Animal testing is no cause for threats

By Stan Nosek and Dallas Hyde

Special to The Bee, Published: Saturday, May. 24, 2008

The Sacramento Bee published an op-ed piece by Vice Chancellor Stan Nosek and Dallas Hyde, director of the California National Primate Research Center at UC Davis, on Saturday drawing attention to the increasing problem of "animal rights" activism and the steps the university is taking to protect medical researchers and their work.

Non-human primates vital for neuroscience research

May 16th, 2008 - 3:28 pm ICT by admin -

London, May 16 (ANI): Monkeys have long been used as an alternative to humans for various experimental studies, and now a new review has backed the concept by claiming that non-human primates will continue to be a significant, if small, part of neuroscience research.

In the review, researchers at California National Primate Research Center have said that studies dealing with non-human primates have greatly helped their understanding of the brain and will continue to be an important, if small, part of neuroscience research. The researchers believe that the role of non-human primates in studies of Alzheimer’s disease, Parkinson’s disease, neurological complications of AIDS and stress is very important.

"The key contribution of these studies is based on the similarities between the brains of humans and those of non-human primates," Lancet quoted John P. Capitanio, UC Davis and associate director of the California National Primate Research Center, as saying.

One can easily see that the organisation and structure of Human and monkey brains is quite similar and that the animals display human like complex behaviour. But, according to Capitanio, the number of animals used will always be limited owing to various complicating factors, like the financial expense, ethical issues and the relative difficulty involving the breeding, which is different from other model animals such as rodents. He further added that all animal models do have their strengths and limitations, but animal models can help researchers understand body systems in the same way as a model building helps engineers and architects understand how a structure will work.

He explained it by giving example of the drug MPTP, which was first synthesized in an illegal drug laboratory and led to symptoms similar to Parkinson’s disease in both humans and monkeys, but not in rats or mice, which lack a crucial enzyme.

And now, the researchers are studying monkeys treated with MPTP in order to have a better understanding of new treatments for Parkinson’s disease, the second most common neurodegenerative disease in people over 65.

"A model is not the real thing, but it can help you understand the real thing," said Capitanio.

The study is published in the British medical journal, The Lancet. (ANI)
February 2008     Autistic Behaviors In Offspring Linked To Prenatal Exposure To Maternal Antibodies

Excerpt from: 12 Feb 2008

http://www.medicalnewstoday.com and ScienceDaily, http://www.sciencedaily.com

New research from the UC Davis M.I.N.D. Institute shows that an interaction between fetal brain cells and maternal antibodies could be linked with the repetitive behavior - also called stereotypies - that is characteristic of autism. While additional studies are needed to confirm the outcome, this result leads investigators to suspect that brain-directed antibodies during the prenatal period could be a causal factor for the disorder.

"Dr. Van de Water’s result implicated maternal immune system factors with at least one form of autism. We wanted to take that important finding a step further and find out if IgG exposure during pregnancy could cause the kinds of changes in social interactions or behavior we see in children with autism." David Amaral

Stereotypies and hyperactivity in rhesus monkeys exposed to IgG from mothers of children with autism. L.A. Martin, P. Ashwood, D. Braunschweig, M. Cabanlit, J. Van de Water, D.G. Amaral. Brain Behav Immun. Feb 7, 2008.

'Til Death Do Us Part

From: Scientific American Mind

February 2008 Issue, by Emily Anthes

When it comes to studying love, prairie voles, with their strong pair bonds, are the laboratory stars. Now researchers at the University of California, Davis, have established a primate model of monogamy they believe will be more relevant for uncovering the basis of human affection. The researchers used PET scans to examine brain activity in male titis, small South American monkeys that form strong relationships with their mates. They discovered that lone, unpaired male titis had strikingly different patterns of brain activity than males in long-term, monogamous partnerships did. These differences were primarily found in two brain circuits: one that is involved in reward processing and another that plays a part in social recognition. These circuits appear to be necessary for pair bonding, lead researcher Karen L. Bales says. And although the regions are also implicated in rodent models of monogamy, she believes titi monkeys will ultimately be more useful for studying human bonding and social disorders, such as autism. The scientists also studied the brains of lone males who had recently been introduced to new mates. Although the average of the monkeys’ brain activity was somewhere in between that of unpaired males and that of those in long-term partnerships, testing showed tremendous individual variation in both behavior and brain activity. "I think we can all identify with that as humans," Bales says. "It’s not always love at first sight."
December 2007     Antibacterial Chemical Disrupts Hormone Activities

Excerpt from: December 7, 2007, UCD Dateline

A new UC Davis study shows that a common antibacterial chemical added to bath soaps can alter hormonal activity in rats and in human cells in the laboratory -- and does so by a previously unreported mechanism. Called endocrine disruptors, or endocrine disrupting substances (EDS), such chemicals have been linked in animal studies to a variety of problems, including cancer, reproductive failure and developmental anomalies.

This is the first endocrine study to investigate the hormone effects of the antibacterial compound triclocarban (also known as TCC or 3,4,4’-trichlorocarbanilide), which is widely used in household and personal care products including bar soaps, body washes, cleansing lotions, wipes and detergents. Triclocarban-containing products have been marketed broadly in the United States and Europe for more than 45 years; an estimated 1 million pounds of triclocarban are imported annually for the U.S. market.

"This finding may eventually lead to an explanation for some rises in some previously described reproductive problems that have been difficult to understand." Dr. Bill Lasley, a UC Davis expert on reproductive toxicology and professor emeritus of veterinary medicine.

Consumers should not take this study as guidance on whether to use triclocarban-containing products, Lasley said. "Our mothers taught us to wash our hands well before the advent of antimicrobial soaps, and that practice alone prevents the spread of disease."

"Triclocarban enhances testosterone action: A new type of endocrine disruptor?", Bill Lasley, Jiangang Chen, Ki Chang Ahn, Nancy Gee, Mohamed I. Mohamed, Antoni Duleba, Ling Zhao, Shirley Gee and Bruce Hammock, Endocrinology, http://endo.endojournals.org/rep.shtml