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Vol. 8 No. 2, 2011 [PDF] - Texas Biomedical Research Institute

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Improving Quality of Life by Studying Fetal Development<br />

Peter Nathanielsz, M.D., Ph.D., has been investigating<br />

the connection between in utero development and health<br />

throughout the lifespan since the 1970s. Working on the<br />

premise that developmental programming creates the<br />

landscape in which you will live the rest of your life, he<br />

has examined the effect of maternal undernutrition and<br />

overnutrition on offspring, and how normal and elevated levels<br />

of the stress hormone, cortisol, affect fetal development. He<br />

began to pursue these current lines of research in 2002, with<br />

funding from a National <strong>Institute</strong>s of Health program project<br />

grant (“Nutrient Restriction,” P01 HD021350).<br />

While the role of developmental programming has been<br />

discussed with increasing frequency in the popular press,<br />

Nathanielsz worries that not enough context is presented to<br />

empower women and families to make informed choices. “The<br />

way I work scientifically is that I first try to ask a question<br />

and then seek hard scientific data to answer it. What are the<br />

potential later life health problems for children of overweight<br />

and obese mothers What are the consequences to children<br />

when their mothers are exposed to excessive amounts of stress<br />

The Round-Up<br />

Director’s Letter<br />

On February 1, <strong>2011</strong>, the name<br />

of SNPRC’s host institution<br />

was changed from Southwest<br />

Foundation for <strong>Biomedical</strong><br />

<strong>Research</strong> to <strong>Texas</strong> <strong>Biomedical</strong><br />

<strong>Research</strong> <strong>Institute</strong>. This name<br />

change coincides with the<br />

initiation of efforts to implement a<br />

recently completed campus master<br />

plan in which the construction of<br />

new buildings for the SNPRC is<br />

prominently featured. The new buildings will provide stateof-the-art<br />

laboratories for SNPRC scientists and will enable an<br />

increase in staff and an expansion of research activities within<br />

in pregnancy” Nathanielsz and others in<br />

this field have been accused of making<br />

women feel guilty. But, he notes “Women<br />

aren’t the only ones involved in pregnancy;<br />

in reality the whole of society has a<br />

responsibility to understand the biology of<br />

pregnancy and how to improve outcomes<br />

and avoid problems. We are talking about<br />

biology, not blame or fault.” The nine months of gestation are<br />

so critical because “What happens in the womb determines the<br />

rate at which you age, your response to stress, your response<br />

to food intake, your predisposition to obesity, diabetes,<br />

cardiovascular disease.”<br />

This approach has led Nathanielsz to examine the longterm<br />

impact of synthetic glucocorticoids given to women<br />

in premature labor. The hormone crosses the placental<br />

barrier and accelerates the development of the fetal lungs,<br />

ripening them in preparation for taking the first breath after<br />

birth. This treatment has been used to save thousands of<br />

lives since 1973, when G.C. Liggins in New Zealand first<br />

(Continued on page 8)<br />

In this Issue<br />

(Continued on page 4)<br />

the Center. As the campus master plan was being finalized,<br />

several major renovation projects were initiated to improve<br />

our primate group housing and to expand cage space for<br />

experimental work.<br />

Baboons.--Group housing is being improved by<br />

the renovation of the walls of the B and E cage complexes<br />

(29,340 sq.<br />

ft.), under funding<br />

($467,000) from an<br />

NCRR G20 grant.<br />

These cages house<br />

approximately 725<br />

baboons from our<br />

pedigreed breeding<br />

colony.<br />

2 Teacher Enrichment Initiative<br />

3 Staff Focus<br />

5 Summer Interns<br />

6 News Round Up<br />

8 <strong>No</strong>tices


2<br />

<strong>Vol</strong>ume 8, <strong>No</strong>. 2, <strong>2011</strong><br />

Teacher Enrichment Initiatives Update<br />

Some area high school science teachers who visited SNPRC<br />

this summer to learn about the role of animals in biomedical<br />

research have found a fun way to enrich the lives of our<br />

chimpanzees. Using funds from the TEI program at UTHSCSA,<br />

teachers at New Braunfels High School and Pearsall High<br />

Scholl created piñatas for the animals this fall. The piñatas<br />

will be filled with nutritious food enrichment at SNPRC and<br />

provided to the animals as a fun treat. The goal with this project<br />

is to “give teachers and students an appreciation for the work<br />

we do to ensure the psychological well-being of our nonhuman<br />

primates who participate in biomedical research conducted at<br />

the SNPRC,” says Corrine Lutz, the head of the Behavioral<br />

Services group.<br />

An East Central ISD student creates a piñata.<br />

HOW TO MAKE A PIÑATA<br />

Chimpanzees enjoy tearing apart the piñata almost as much as<br />

they enjoy eating the seeds and other treats inside.<br />

The Round-Up<br />

is published twice a year by the Southwest<br />

National Primate <strong>Research</strong> Center.<br />

John L. VandeBerg, Director<br />

P.O. Box 760549, San Antonio, <strong>Texas</strong> 78245-0549<br />

Phone: 210-258-9780 Fax: 210-258-9883 http://www.snprc.org<br />

This newsletter provides updates on scientific research and activities<br />

supported by the National Center for <strong>Research</strong> Resources, National <strong>Institute</strong>s<br />

of Health. We welcome inquiries about our biomedical research program and<br />

collaborative opportunities for outside investigators.<br />

April Hopstetter, Editor Copyright <strong>2011</strong><br />

Ph: 210-258-9519<br />

Southwest National Primate <strong>Research</strong> Center<br />

Fax: 210-258-9863<br />

E-mail: ahopstet@TxBiomed.org<br />

1. Cut butcher paper into 1 ½ inch strips<br />

2. Fill tub with water<br />

3. Add flour and mix until thick<br />

4. Blow up and tie balloons<br />

5. Use plastic containers as stands for balloons<br />

6. Soak paper strips in tub and coat them<br />

thoroughly with flour water mixture<br />

7. Layer strips of paper around balloon<br />

8. Add 2 layers of paper strips<br />

9. Store on containers over night, or until dry and<br />

hard<br />

HOW TO PAINT A PIÑATA<br />

1. Paint solid base coat with any color non-toxic<br />

paint<br />

2. Allow to dry<br />

3. Use multi-colored paints to create various<br />

designs<br />

4. Allow to dry, placing piñata on a plastic or<br />

cardboard container<br />

5. Balloons will shrink over time and pull away<br />

from the paper<br />

6. Finished piñatas may be stored and transported<br />

in large plastic trash bags


The Round-Up 3<br />

Staff Focus: Jera Pecotte, Ph.D.<br />

Jera Pecotte, Ph.D., fulfills many roles in<br />

the SNPRC. She oversees the biomaterials<br />

distribution program and a variety of training and<br />

internship programs. Dr. Pecotte began her career<br />

working in forensic anthropology, providing<br />

support to the Utah State Medical Examiner’s<br />

office. She also worked with ancient Egyptian<br />

remains both in Italy and Egypt. After several<br />

years in Italy directing a U.S. consortium studyabroad<br />

program at the University of Turin, she<br />

returned to the U.S., where friend and colleague<br />

Karen Rice, Ph.D., recruited her to oversee the<br />

burgeoning biomaterials program at SNPRC.<br />

Pecotte was able to use her background in<br />

anatomy immediately. What started as an interim<br />

position has grown over the intervening eight<br />

years. She took over the tissue collection role,<br />

which had begun under the guidance of Henry<br />

McGill, M.D., and expanded over time, and now also oversees<br />

the blood and DNA repository.<br />

Her staff includes Kelly Clark, <strong>Research</strong> Technician II, who<br />

is in charge of order shipping and assists with some tissue<br />

collection; Leilah Minica, Senior <strong>Research</strong> Assistant, who is<br />

in charge of DNA extraction and other “wet lab” work; and<br />

Steve Rios, <strong>Research</strong> Techician III, who is in charge of blood<br />

processing and tissue collection at necropsy. The biomaterials<br />

team ensures that samples are correctly collected, stored or<br />

shipped according to investigator request. Biomaterials works<br />

hand-in-hand with the Pathology group, which often processes<br />

tissues in house for the investigator. Pecotte has also recruited<br />

the assistance of a neuroanatomist consultant from UTSA, Dr.<br />

Clyde Phelix, to dissect out precise brain tissues at necropsy for<br />

complex specialized requests.<br />

Pecotte hopes to continue to increase and diversify the offerings<br />

of the biomaterials service, suggesting that creating RNA on<br />

request, creating RNA assays, or other innovative services,<br />

may be possible. Pecotte interacts with others who maintain<br />

primate repositories and also with the International Society<br />

for Biological and Environmental Repositories, where she can<br />

research practical issues such as best methods for maintaining<br />

inventory, the best receptacles for samples, and optimizing<br />

storage and handling conditions.<br />

Pecotte finds recipients to be very appreciative. “We’ve had offsite<br />

investigators come to visit us to thank us for making their<br />

studies possible. It’s very rewarding.” She is happy to report that,<br />

in most cases, most requests can be fulfilled. They try to ensure<br />

Biomaterials Services Staff (left to right): Jera Pecotte, Steve<br />

Rios, Leilah Minica, and Kelly Clark.<br />

that samples are collected whenever an opportunity arises.<br />

“The effort of maintaining the resource really pays off when<br />

you see someone who is able to do the research they would<br />

not be able to do otherwise. It’s especially true with tissues<br />

from chimpanzees, whose numbers are dwindling in research<br />

environments as well as in the wild. And the fact that we have<br />

pedigrees makes the samples even more valuable,” Pecotte<br />

says.<br />

As the coordinator of the 2010 summer internship program,<br />

Pecotte had undergraduate and graduate students interact<br />

with high school teachers who were on site to learn about<br />

biomedical research using nonhuman primates. As a result of<br />

these interactions, Pecotte says, “The student interns shared<br />

with the teachers what it was in their education that propelled<br />

them into science. And the high school teachers were really<br />

inspiring. Our role in participating with the science teachers<br />

is to help share and teach the value of animals in biomedical<br />

research. Several of our SNPRC core staff gave talks, our<br />

enrichment staff demonstrated behavior and enrichment tasks,<br />

and we also had a member of our Quality Assurance staff<br />

discuss animal welfare regulations governing research.”<br />

“The high school science teachers also had students create<br />

piñatas for the animals that would be filled with food and<br />

other enrichment items at the SNPRC. That allows the<br />

students be part of the process and perhaps be inspired to<br />

pursue careers in research,” Pecotte concludes.


4<br />

<strong>Vol</strong>ume 8, <strong>No</strong>. 2, <strong>2011</strong><br />

Fetal Development (continued from page 1)<br />

reported that prematurely born lambs whose mothers were given<br />

glucocorticoids had better ability to breathe and survive than<br />

untreated animals.<br />

Nathanielsz has reservations about the far-reaching effects<br />

of glucocorticoid administration. “<strong>No</strong> one has done a trial to<br />

determine the optimal dose. I am concerned with the effects<br />

on the kidney, the brain…seeing high levels of glucocorticoid<br />

before they should. Perhaps a lower dose can allow the lungs to<br />

be prepared for breathing while not prematurely signaling the<br />

other organs to differentiate. My thesis, and I’m certainly not<br />

alone, is that you could get adequate lung maturation if you give<br />

a lower dose. And you would also have less of the potentially<br />

harmful effects on the brain, the kidney, the gut, and the heart.”<br />

The benefit conferred by the dose of steroid lasts for a week;<br />

if labor is delayed beyond a week, no benefit is seen. As a<br />

result, physicians sometimes feel compelled to give additional<br />

doses as pregnancy progresses if it appears that the mother<br />

might still deliver prematurely. Though the NIH does not<br />

endorse administering more than one dose, some women<br />

at risk of preterm delivery do get multiple weekly doses of<br />

glucocorticoids. Even more distressing, in some countries,<br />

giving the steroids to mothers has insinuated itself into the<br />

standard of care even in the absence of any threat of early<br />

delivery. The implications of excessive and unnecessary<br />

exposure of the developing fetus to steroids are serious. When<br />

fetal organs differentiate early following early exposure to<br />

steroids they then have fewer cells and can be more prone to<br />

problems in later life. For example, a smaller pancreas can lead<br />

to diabetes if the diet in later life is not good.<br />

Until a few years ago, there was no evidence of adverse<br />

effects of prenatal glucocorticoid administration on long-term<br />

development in humans. <strong>No</strong>w those babies are adults, and initial<br />

studies have found a higher incidence of glucose instability and<br />

high blood pressure in the first cohorts that received this therapy.<br />

While these findings took 37 years to amass, a primate model<br />

allows researchers to answer scientific questions more quickly:<br />

a baboon reaches puberty in 4 years; a human reaches puberty in<br />

14 years.<br />

Nathanielsz and his team are examining the “cost” of exposure<br />

to high levels of glucocorticoids in fetal life using the baboon as<br />

a model. “In our study, we’re administering the glucocorticoid,<br />

letting the mothers deliver, then we’re looking at the behavior<br />

of the offspring. The three-year-old baboons we are studying<br />

were exposed to high levels of glucocorticoid when in the<br />

womb. We are asking several questions using these offspring.<br />

Has the exposure had any effect on behavior, the pancreas, the<br />

kidney or the gut” Collaborator Mark Nijland, Ph.D., has<br />

Fetal baboon hippocampus stained for microtubular associated protein<br />

2c (MAP2c; brown stain). The hippocampus regulates memory, adrenal<br />

function and many behaviors. Brain tissue from a control late gestation<br />

baboon fetus (left) displays more MAP2c than the hippocampus of a<br />

baboon fetus whose mother received doses of steroids equivalent to<br />

those given in human pregnancy (right).<br />

adapted a behavioral testing system used with young children<br />

to use in the baboon to answer some of these questions, while<br />

SNPRC Core Scientist Laura Cox, Ph.D., is looking at gene<br />

expression to see how it varies between treated and untreated<br />

baboons. Preliminary data indicate that there are differences in<br />

offspring behavior, which are related to sex of the offspring,<br />

at an age equivalent to human adolescence. When studied<br />

in a behavioral test that measures motivation, betamethasone<br />

exposure decreased motivation in both sexes. In a test that<br />

evaluates attention allocation, female offspring exposed to<br />

steroids committed more errors than males. Nathanielsz hopes<br />

these data will help to reopen the dialog with the medical<br />

profession to determine dose of steroid to use to obtain<br />

maximal benefit. “We’ve shown in the pregnant sheep that<br />

half of the dose is adequate for maturing the lungs. Our goal<br />

is not to stop the administration of glucocorticoids to women<br />

threatening to deliver early. This treatment has saved the lives<br />

of countless babies and decreased neonatal problems. But<br />

it is clear that work needs to be done to optimize the dose,”<br />

Nathanielsz says.<br />

“Unless we get firm evidence about the long-term adverse<br />

consequences for normal fetal development of fetal exposure<br />

to glucocorticoids, nothing will change. That’s why we need<br />

sound, careful controlled animal research.” Nathanielsz<br />

concludes.<br />

Peter W. Nathanielsz, M.D., Ph.D., is the Director of the Center for<br />

Pregnancy and Newborn <strong>Research</strong> and Professor in the Department<br />

of Obstetrics and Gynecology, University of <strong>Texas</strong> Health Science<br />

Center, San Antonio.<br />

SELECTED PUBLICATIONS<br />

Nathanielsz PW, Berghorn KA, Derks JB, Giussani DA, Docherty C,<br />

Unno N, Davenport A, Kutzlers M, Koenen S, Visser GH, Nijland<br />

MJ. Life before birth: effects of cortisol on future cardiovascular<br />

and metabolic function. Acta Paediatr. 2003;92(7):766-72.<br />

Nijland MJ. Fetal exposure to corticosteroids: how low can we go J<br />

Physiol. 2003;549(Pt 1):1.<br />

Rodriguez JS, Zürcher NR, Keenan KE, Bartlett TQ, Nathanielsz PW,<br />

Nijland MJ. Prenatal betamethasone exposure has sex specific<br />

effects in reversal learning and attention in juvenile baboons. Am J<br />

Obstet, in press.


The Round-Up 5<br />

Summer 2010 Intern Update<br />

As national resources, the National Primate <strong>Research</strong><br />

Centers are in a unique position to provide training<br />

opportunities to students by providing extensive and varied<br />

opportunities in biomedical research and laboratory animal<br />

care. The need for nonhuman primates in biomedical<br />

research is increasing at a rapid pace as translational research<br />

funding is committed to critical areas such as biodefense,<br />

stem cell development, and gene therapy. This summer’s<br />

students conducted research in virology, immunology,<br />

diseases of aging, and pathology under the guidance of their<br />

SNPRC mentors. The following summarizes each student’s<br />

research.<br />

David Cray, an undergraduate at the University of <strong>No</strong>tre<br />

Dame, worked under the supervision of veterinarians<br />

Heather Cole, D.V.M., Patrice Frost, D.V.M., and Cassie<br />

Bauer, D.V.M. He studied the prevalence and speciation of<br />

Babesia infection in the baboon colony using archived samples.<br />

Drs. Adam Birkenheuer and Anna Stedman of <strong>No</strong>rth Carolina<br />

State University assisted in the genetic identification of Babesia<br />

samples and PCR testing. Future studies may include further<br />

assessment of prevalence and distribution and determination of<br />

the mode of transmission.<br />

Benjamin Fox, an undergraduate at <strong>Texas</strong> A&M University<br />

working toward a degree in biomedical science, worked under<br />

the supervision of pathologists Mike Owston, D.V.M., and<br />

Edward Dick, D.V.M. in the pathology laboratory. He also<br />

worked on a research project, examining 26 years of clinical<br />

records to characterize congenital lesions in baboons. Findings<br />

indicate that the baboon has an incidence of congenital lesions<br />

similar to humans. They will be developed into a manuscript to<br />

be submitted to a peer-reviewed journal.<br />

Antonio Gonzalez, a second-year undergraduate at the<br />

University of Puerto Rico, Mayaguez, worked under the<br />

supervision of Melissa de la Garza, D.V.M. He studied<br />

cardiovascular disease in chimpanzees, examining the<br />

relationship between measures of brain natriuretic peptide (BNP)<br />

and the characteristics of electrocardiograms to see whether BNP<br />

levels correlate to heart health. He found sex-related, but not<br />

weight-related differences in BNP levels, but the small sample<br />

size of 5 animals precluded making definitive conclusions.<br />

BNP levels also seemed to be related to cardiac arrhythmias<br />

and circulatory problems, but seems best suited to serve as a<br />

supplemental metric to use in a diagnostic workup.<br />

Shyamesh Kumar, D.V.M., a graduate student in the College<br />

of Veterinary Medicine of Mississippi State University, worked<br />

under the supervision of Ed Dick, D.V.M. He assisted with<br />

Summer, 2010 Interns and Mentors (left to right): Fabian<br />

Vazquez-Santiago, Shyamesh Kumar, Luis Giavedoni,<br />

Benjamin Fox, Edward Dick, Michael Owston, Antonio<br />

Gonzalez, Cassondra Bauer, David Cray, Melissa de la<br />

Garza, Heather Cole, Ashley Lipps, and Elizabeth Dick<br />

(volunteer).<br />

necropsies and also performed a retrospective investigation<br />

of archived materials to examine cases of encephalitis of<br />

unknown cause in the baboons. He was able to determine<br />

the cause definitively in a majority of cases. Findings will<br />

be developed into a manuscript to be submitted to a peerreviewed<br />

journal.<br />

Ashley Lipps, a third-year graduate student studying<br />

biological anthropology at the University of California,<br />

Berkeley, worked under the supervision of Lorena Havill,<br />

Ph.D. She gathered research data related to her dissertation,<br />

which examines how reproduction reorganizes bone on a<br />

microcellular level. She gathered archived bone samples<br />

from 142 baboon and reviewed the reproductive history of<br />

the females in the pedigreed baboon colony. Analyses are<br />

being completed at Berkeley, but Lipps will return to collect<br />

additional samples later.<br />

Fabian Vazquez-Santiago a first-year graduate student<br />

at Ponce School of Medicine, Puerto Rico, worked under<br />

the supervision of Luis Giavedoni, Ph.D. He broadened<br />

his laboratory experience by constructing viral vectors that<br />

includes “instructions” necessary to generate fusion proteins<br />

that may be used to bind to certain sites on immune system<br />

cells that are targets of SIV, the monkey equivalent of HIV.<br />

The vectors constructed and determined to be functional<br />

as part of this effort will be used to evaluate the macaque’s<br />

immune response to SIV infection.


6<br />

Presentations and Invited Talks at SNPRC<br />

June 2010 - <strong>No</strong>vember 2010<br />

“Hepatitis C and the Chimp Model,” June 29, 2010, Dr.<br />

Robert Lanford, SNPRC Core Scientist, held at the University<br />

of <strong>Texas</strong> Health Science Center<br />

“Trypanosomes and Chagas disease in Ecuador: From basic<br />

research to control interventions,” Thursday, July 8, 2010,<br />

Mauricio Lascano, Ph.D., International Emerging Infectious<br />

Diseases Fellow, Division of Parasitic Diseases, Centers for<br />

Disease Control and Prevention, Atlanta, GA<br />

“Identification of genetic networks underlying cardiovascular<br />

disease phenotypes,” August 13, 2010, Dr. Laura Cox, at the<br />

First Genome <strong>Research</strong> Day, held at the University of <strong>Texas</strong><br />

Health Science Center<br />

“Understanding the genetic and epigenetic complexities of<br />

brain structure and function,” August 19, 2010, Dr. Melanie<br />

Carless, Assistant Scientist, Department of Genetics, SFBR<br />

“Multi-Epitope DNA Vaccines Against Ebola Virus,”<br />

September 7, 2010, Dr. Daniel A. J. Mitchell, Ph.D., U.S.<br />

Army Medical <strong>Research</strong> <strong>Institute</strong> of Infectious Diseases<br />

(USAMRIID), Fort Detrick, Maryland<br />

“Viral Forecasting,” October 15, 2010, Dr. Nathan Wolfe,<br />

Lorry I. Lokey Visiting Professor in Human Biology<br />

at Stanford University and Director of the Global Viral<br />

Forecasting Initiative<br />

“Challenges and opportunities in AIDS vaccine development,”<br />

October 15, 2010, Dr. Wayne C. Koff, Chief Scientific<br />

Officer, Senior Vice President , <strong>Research</strong> and Development ,<br />

International AIDS Vaccine Initiative<br />

“Evolution of splicing in primates,” October 19, 2010, Dr. Yi<br />

Xing, Assistant Professor, Departments of Internal Medicine<br />

and <strong>Biomedical</strong> Engineering, University of Iowa.<br />

“Using Genetics and Stem Cell Therapy to Guide Personalized<br />

Medicine,” October 28, 2010, Dr. Kang Zhang, Professor of<br />

Ophthalmology & Human Genetics, University of California,<br />

San Diego<br />

“Genetics of age-related macular degeneration,” <strong>No</strong>vember<br />

18, 2010, Dr. Peter Francis, Associate Professor, Co-Director,<br />

Oregon Retinal Degeneration Center, Oregon Health &<br />

Science University<br />

<strong>Vol</strong>ume 8, <strong>No</strong>. 2, <strong>2011</strong><br />

Nathan Wolfe visits<br />

SNPRC<br />

On October 14 and 15, 2010,<br />

Dr. Nathan Wolfe, Director of<br />

the Global Viral Forecasting<br />

Initiative (GVFI), visited<br />

the SNPRC. He gave a talk<br />

on “Viral Forecasting” to<br />

an enthusiastic crowd. He<br />

discussed how new methods<br />

of surveillance were being<br />

developed and would be used in<br />

the future to identify emerging<br />

diseases before they became<br />

epidemics.<br />

Dr. Wolfe also met with<br />

SNPRC and SFBR scientists<br />

to discuss future collaborations<br />

utilizing some of the new<br />

epidemiological tools he was developing. The goal of the<br />

trip was to better acquaint Dr.Wolfe with SFBR’s interests<br />

and capabilities as well as introduce SFBR scientists to a new<br />

exotic panel of biologically characterized reagents that Dr.<br />

Wolfe has collected.<br />

According to its web site (www.gvfi.org), “GVFI is a<br />

pandemic early warning system which monitors the spillover<br />

of novel infectious agents from animals into humans. GVFI<br />

coordinates activities of over 100 scientists and staff from<br />

countries around the world. He currently has active research<br />

and public health projects in Cameroon, China, Central African<br />

Republic, DR Congo, PR Congo, Gabon, Equatorial Guinea,<br />

Lao, Madagascar, Malaysia and Sao Tome.”<br />

Tom Folks, Ph.D., Associate Director for <strong>Research</strong> Resources,<br />

SNPRC, along with SFBR, hosted Dr. Wolfe, and notes “Dr.<br />

Wolfe and I have interacted for over 12 years identifying and<br />

characterizing emerging retroviruses. One of our most recent<br />

patents and publications describes the full genomic sequence<br />

of our latest discovery, HTLV-4, isolated from a human in<br />

Central Africa.” Ancient, independent evolution and distinct<br />

molecular features of the novel human T-lymphotropic virus<br />

Type 4, Switzer et al., Retrovirology 2009, 6:9 (2 Feb. 2009).<br />

It is hoped that the outcome of Dr. Wolfe’s visit will inspire<br />

SFBR scientists to actively engage with GVFI to expand our<br />

knowledge of emerging infectious diseases.


The Round-Up 7<br />

<strong>No</strong>nhuman primates<br />

advance AIDS research<br />

Tom Folks, Associate<br />

Director for <strong>Research</strong><br />

Resources, contributed a<br />

“Perspective” article to<br />

the Journal of Medical<br />

Primatology (40(1):59-<br />

60, <strong>2011</strong>). Entitled “AIDS<br />

Animal Model Comes<br />

of Age,” it addresses the<br />

critical need for a reliable<br />

animal model to study<br />

AIDS and to investigate<br />

promising preventative<br />

therapies.<br />

The premise of this article has been borne out by two<br />

prominent human clinical trials that have been published in the<br />

scientific literature in the past few months. Results of a human<br />

clinical trial for HIV prevention using Truvada (Tenofovir +<br />

FTC) gel as a microbicide appeared in Science in <strong>No</strong>vember<br />

2010, and they validate for the first time a macaque model<br />

designed to investigate prevention of virus transmission. The<br />

study was patterned after one conducted using the rhesus<br />

macaque model that aimed to prevent mucosal transmission,<br />

and on which Dr. Folks served as an investigator.<br />

The second human study was published on line in The<br />

New England Journal of Medicine. It was conducted by the<br />

Preexposure Prophylaxis Initiative (iPrEx) and used Truvada<br />

as an HIV pre-exposure prophylaxis. The drug was delivered<br />

orally and was able to prevent up to 75% of new HIV<br />

infections if taken properly. This study arose from a successful<br />

primate model study using oral Truvada prophylaxis in which<br />

Dr. Folks also served as an investigator.<br />

“As a prevention tool, the macaque has provided the critical<br />

guidance in directing two breakthrough clinical trials in<br />

blocking two modes of HIV transmission. These findings<br />

advance the rhesus macaque model as a starting point to test<br />

the next generation of HIV prevention therapies,” says Dr.<br />

Folks, who continues, “Macaques as an AIDS animal model<br />

will continue to contribute important translational information<br />

as new drugs, possibly superior to Truvada, enter the HIV preexposure<br />

prevention pipeline.”<br />

Promotions for <strong>2011</strong><br />

Congratulations to the following employees on their<br />

outstanding efforts!<br />

Manuel Aguilar -- Veterinary <strong>Research</strong> Technician III<br />

Joshua Bingham -- Veterinary <strong>Research</strong> Technician II<br />

Michael Shaun Cawlfield -- Veterinary <strong>Research</strong> Technician II<br />

Kelly A. Clark -- <strong>Research</strong> Technician II<br />

Jacob E. Martinez -- Necropsy Technician I<br />

Jesse C. Martinez -- Necropsy Technician I<br />

Cynthia Mermeia -- <strong>Research</strong> Associate<br />

Abel Moncivais -- Veterinary <strong>Research</strong> Technician III<br />

Christian Heath Nevill -- Senior <strong>Research</strong> Associate<br />

Steve Rios -- <strong>Research</strong> Technician III<br />

Laura Rumpf -- Veterinary <strong>Research</strong> Technician III<br />

Ashley Smith -- Veterinary <strong>Research</strong> Technician I<br />

Lateya Smith -- Veterinary <strong>Research</strong> Technician III<br />

Maribel Vazquez -- <strong>Research</strong> Associate<br />

Michael Washington-- Veterinary <strong>Research</strong> Technician III<br />

National AALAS Meeting, Atlanta, GA<br />

On October 10-14, 2010 members of the National American<br />

Association of Laboratory Animal Science (AALAS) met<br />

in Atlanta, GA, and as a perk of her winning the Technician<br />

Assistance Award at the <strong>Texas</strong> Branch AALAS, Annessa<br />

Raiford attended the National AALAS Meeting. Other<br />

SNPRC attendees included: Dr. Lutz, Jennifer Smith.<br />

We have formed a Training Program Development Task<br />

Force to facilitate the development of the training program.<br />

Members include Brooke Stotler, Sharon Price, Dr. Bauer,<br />

Tim Fleming, Don Taylor, and Laurie Condel. Anyone with<br />

questions or suggestions can contact any of the members.<br />

Interested in AALAS Certification<br />

AALAS offers three levels of certification, based on<br />

education and experience. To learn more, go to<br />

http://www.aalas.org/certification/tech_cert.asp. SNPRC<br />

pays for study materials and the exam fee for one exam<br />

per level. Supervisors have also organized study groups for<br />

ALAT, LAT, and LATg testing. Interested staff members<br />

should contact Brooke Stotler or their supervisors for more<br />

information or visit http://info.txbiomed.org/index.php/<br />

vet-resources/learning


Director’s Letter<br />

(Continued from page 1)<br />

Rhesus monkeys.--Building 114 (5,253 sq. ft.) is being<br />

extensively upgraded to enable expansion of our SPF rhesus<br />

monkey breeding colony, under ARRA supplemental funding<br />

($524,000) to the U42 grant that partially supports the colony.<br />

In addition, extensive floor improvements of the existing<br />

breeding facility (14,332 sq. ft.) are in progress, supported by<br />

funding ($404,289) from a G20 grant. Building 4 is being fully<br />

renovated to provide ABSL-2 housing for macaques, as well as<br />

baboons, in experimental protocols, under support ($443,000)<br />

from a G20 grant. Cages for Building 4 are being purchased<br />

with funds ($474,000) from another G20 grant.<br />

Chimpanzees.--All of the existing chimpanzee<br />

facilities are being renovated under support from a supplement<br />

($499,995) to the base grant, and a new chimpanzee facility<br />

(12,346 sq. ft.) is being developed by renovating Building 112,<br />

which had previously housed cynomolgus monkeys, under<br />

support ($1,460,000) from a C06 grant.<br />

These major improvements and expansions of primate<br />

group and experimental housing will enable us to continue<br />

providing high quality care to the primates and to significantly<br />

expand the research and breeding programs conducted by our<br />

Core Scientists as well as by Affiliate Scientists from around the<br />

country.<br />

New Training Coordinator at SNPRC<br />

SNPRC welcomed new training coordinator Brooke Stotler,<br />

LAT, in August of this year. She’s been making the rounds,<br />

talking to coworkers in all areas of the SNPRC, and learning<br />

about processes in place and needs for training.<br />

Stotler comes to the SNPRC after working many years at a<br />

contract research organization. She will use her background<br />

in animal care in a GLP environment to formalize the exisitng<br />

training program, enhance its offerings, and continue the<br />

successful onsite AALAS certification test preparation. Stotler<br />

is currently updating AALAS materials and organizing the<br />

next sessions of . Classes for all 3 levels scheduled to begin in<br />

January <strong>2011</strong>.<br />

She also plans to coordinate “as needed” training on special<br />

topics, and encourages supervisors to discuss needs with her.<br />

Suggestions for special topics include working with certain<br />

programs, data entry and review, computer use (basic, use of<br />

Excel, and other programs) and improving writing skills.<br />

When asked to describe her training philosophy, Stotler says,<br />

“I believe in learning all of the time. I want to be able to share<br />

new skills and transmit my enthusiasm to everyone I work<br />

with.”<br />

Pilot Study Program<br />

New, innovative pilot studies have the potential for<br />

developing into larger projects that could then compete<br />

for funds on their own. In the past the SNPRC has been<br />

very successful in supporting and sponsoring from 2<br />

to 4 Pilot Studies per year. A high percentage of those<br />

studies have then been leveraged into larger NIH grants.<br />

Unfortunately, due to financial constraints, the SNPRC<br />

will not be accepting applications for Pilot Study projects<br />

to be initiated in <strong>2011</strong>. We hope that the program will be<br />

reinstated in 2012.<br />

Summer Intern Program<br />

In previous years, SNPRC has provided educational and<br />

training opportunities for a limited number of students<br />

during an 8-10 week summer session. Both undergraduate<br />

and graduate (Ph.D. and veterinary) students at accredited<br />

academic institutions have participated. The program<br />

has produced some outstanding research opportunities<br />

for budding scientists. Unfortunately, due to financial<br />

constraints, SNPRC will not be able to offer the Summer<br />

Intern program this year. We hope that we will be able to<br />

reinstate the program in 2012.


SNPRC Publications<br />

June 2010 – <strong>No</strong>vember 2010<br />

Core Staff Publications<br />

Biesinger T, White R, Yu Kimata MT, Wilson BK, Allan JS, Kimata JT.<br />

Relative replication capacity of phenotypic SIV variants during primary<br />

infections differs with route of inoculation. Retrovirology. 2010 Oct 13;<br />

7: 88. PMCID: PMC2964591.<br />

Bose T, Voruganti VS, Tejero ME, Proffit JM, Cox LA, VandeBerg<br />

JL, Mahaney MC, Rogers J, Freeland-Graves JH, Cole SA,<br />

Comuzzie AG. Identification of a QTL for adipocyte volume and of<br />

shared genetic effects with aspartate aminotransferase. Biochem Genet.<br />

2010 Jun; 48(5-6): 538-547. PMCID: PMC2869397.<br />

Cerbulo-Vazquez A, Zavala M, Perez-Palacios GA, Jenkins SL,<br />

Giavedoni LD, Hodara VL, Romero R, Wimmer RD, Irles C,<br />

Nathanielsz PW. Baboon fetal arterial endothelial cells are more<br />

responsive to challenge by tumor necrosis factor alpha (TNF-α) than<br />

baboon fetal umbilical vein endothelial cells. Atherosclerosis. 2010 Oct;<br />

212(2): 701-703. PMCID: PMC2952702.<br />

Higgins PB, Bastarrachea RA, Lopez-Alvarenga JC, Garcia-Forey M,<br />

Proffitt JM, Voruganti VS, Tejero ME, Mattern V, Haack K, Shade<br />

RE, Cole SA, Comuzzie AG. Eight week exposure to a high sugar high<br />

fat diet results in adiposity gain and alterations in metabolic biomarkers<br />

in baboons (Papio hamadryas sp.). Cardiovasc Diabetol. 2010 Oct 29;<br />

9: 71. PMCID: PMC2988722.<br />

Hlusko LJ, Sage RD, Mahaney MC. Modularity in the mammalian<br />

dentition: Mice and monkeys share a common dental genetic<br />

architecture. J Exp Zool B Mol Dev Evol. 2010 Oct 4.<br />

Holmes RS, Cox LA, VandeBerg JL. Comparative studies of mammalian<br />

acid lipases: Evidence for a new gene family in mouse and rat (lipo).<br />

Comp Biochem Physiol Part D Genomics Proteomics. 2010 Sep; 5(3):<br />

217-226. PMCID: PMC2917524.<br />

Holmes RS, Cox LA, VandeBerg JL. Mammalian carboxylesterase 3:<br />

Comparative genomics and proteomics. Genetica. 2010 Jul; 138(7):<br />

695-708. PMCID: PMC2896070.<br />

Kamat A, Nijland MJ, McDonald TJ, Cox LA, Nathanielsz PW, Li C.<br />

Moderate global reduction in maternal nutrition has differential stage of<br />

gestation specific effects on β1- and β2-adrenergic receptors in the fetal<br />

baboon liver. Reprod Sci. 2010 <strong>No</strong>v 15.<br />

Karere GM, Glenn JP, VandeBerg JL, Cox LA. Identification of<br />

baboon microRNAs expressed in liver and lymphocytes. J Biomed Sci.<br />

2010 Jul 1; 17: 54. PMCID: PMC2905361.<br />

Keckler MS, Hodara VL, Parodi LM, Giavedoni LD. Maintenance or<br />

emergence of chronic phase secondary cytotoxic T lymphocyte<br />

responses after loss of acute phase immunodominant responses does not<br />

protect SIV-infected rhesus macaques from disease progression. J<br />

Biomed Biotechnol. 2010; 2010: 279391. PMCID: PMC2877203.<br />

Kochunov P, Glahn DC, Fox PT, Lancaster JL, Saleem K, Shelledy W,<br />

Zilles K, Thompson PM, Coulon O, Mangin JF, Blangero J, Rogers J.<br />

Genetics of primary cerebral gyrification: Heritability of length, depth<br />

and area of primary sulci in an extended pedigree of Papio baboons.<br />

Neuroimage. 2010 <strong>No</strong>v 15; 53(3): 1126-1134. PMCID: PMC2888833.<br />

Koh C, Bates E, Broughton E, Do NT, Fletcher Z, Mahaney MC, Hlusko<br />

LJ. Genetic integration of molar cusp size variation in baboons. Am J<br />

Phys Anthropol. 2010 Jun; 142(2): 246-260. PMCID: PMC2914092.<br />

Miley DD, Baumgartner MH, Cheverud JM, Roseman CC, Rogers J,<br />

McLeod DE, Reyes E, Hildebolt CF. Heritability of alveolar bone loss<br />

from periodontal disease in a baboon population. A pilot study. J<br />

Periodontol. 2010 <strong>No</strong>v 2.<br />

Mohr EL, Murthy KK, McLinden JH, Xiang J, Stapleton JT. The natural<br />

history of nonhuman GB virus C in captive chimpanzees. J Gen Virol.<br />

<strong>2011</strong> Jan;92(Pt 1):91-100.<br />

Rainwater DL, Shi Q, Mahaney MC, Hodara V, VandeBerg JL, Wang<br />

XL. Genetic regulation of endothelial inflammatory responses in<br />

baboons. Arterioscler Thromb Vasc Biol. 2010 Aug; 30(8): 1628-1633.<br />

PMCID: PMC2908371.<br />

Rainwater DL, VandeBerg JL, Mahaney MC. Effects of diet on genetic<br />

regulation of lipoprotein metabolism in baboons. Atherosclerosis. 2010<br />

Dec;213(2):499-504.<br />

Rivera-Amill V, Kumar R, <strong>No</strong>el RJ, Jr, Garcia Y, Rodriguez IV, Martinez<br />

M, Sariol CA, Kraiselburd E, Iszard M, Mukherji M, Kumar S,<br />

Giavedoni LD, Kumar A. Short communication: Lack of immune<br />

response in rapid progressor morphine-dependent and SIV/SHIVinfected<br />

rhesus macaques is correlated with downregulation of TH1<br />

cytokines. AIDS Res Hum Retroviruses. 2010 Aug; 26(8): 919-922.<br />

PMCID: PMC2957625.<br />

Rogers J, Kochunov P, Zilles K, Shelledy W, Lancaster J, Thompson P,<br />

Duggirala R, Blangero J, Fox PT, Glahn DC. On the genetic<br />

architecture of cortical folding and brain volume in primates.<br />

Neuroimage. 2010 <strong>No</strong>v 15; 53(3): 1103-1108.<br />

Roseman CC, Willmore KE, Rogers J, Hildebolt C, Sadler BE,<br />

Richtsmeier JT, Cheverud JM. Genetic and environmental contributions<br />

to variation in baboon cranial morphology. Am J Phys Anthropol. 2010<br />

Sep; 143(1): 1-12.<br />

Rubio CA, Owston M, Orrego A, Dick EJ, Jr. Further studies on<br />

Barrett’s mucosa in baboons: Metaplastic glandular cells produce<br />

sialomucin. Anticancer Res. 2010 Oct; 30(10): 4123-4126.<br />

Rubio CA, Owston M, Orrego A, Dick EJ, Jr. A simple method to record<br />

parietal cells in the fundic mucosa in baboons. In Vivo. 2010 Sep-Oct;<br />

24(5): 705-707.<br />

Simerly CR, Castro CA, Jacoby E, Grund K, Turpin J, McFarland D,<br />

Champagne J, Jimenez JB, Jr, Frost P, Bauer C, Hewitson L, Schatten<br />

G. Assisted reproductive technologies (ART) with baboons generate<br />

live offspring: A nonhuman primate model for ART and reproductive<br />

sciences. Reprod Sci. 2010 Oct; 17(10): 917-930.<br />

Whittaker C, Grist G, Bert A, Brasky K, Neighbors S, McFall C, Hilbert<br />

SL, Drake WB, Cromwell M, Mueller B, Lofland GK, Hopkins RA.<br />

Pediatric cardiopulmonary bypass adaptations for long-term survival of<br />

baboons undergoing pulmonary artery replacement. J Extra Corpor<br />

Technol. 2010 Sep; 42(3): 223-231.<br />

Widman DG, Ishikawa T, Giavedoni LD, Hodara VL, de la Garza M,<br />

Montalbo JA, Travassos Da Rosa AP, Tesh RB, Patterson JL, Carrion<br />

R, Jr, Bourne N, Mason PW. Evaluation of RepliVAX WN, a singlecycle<br />

flavivirus vaccine, in a non-human primate model of West Nile<br />

virus infection. Am J Trop Med Hyg. 2010 Jun; 82(6): 1160-1167.<br />

PMCID: PMC2877429.<br />

Wonganan P, Clemens CC, Brasky K, Pastore L, Croyle MA. Species<br />

differences in the pharmacology and toxicology of PEGylated helperdependent<br />

adenovirus. Mol Pharm. 2010 Sep 23.<br />

Affiliate Staff Publications<br />

Arroyo JA, Li C, Schlabritz-Loutsevitch N, McDonald T, Nathanielsz<br />

P, Galan HL. Increased placental XIAP and caspase 3 is associated with<br />

increased placental apoptosis in a baboon model of maternal nutrient<br />

reduction. Am J Obstet Gynecol. 2010 Oct; 203(4): 364.e13-364.e18.<br />

PMCID: PMC2947591.<br />

Ben-Yehudah A, Easley CA IV, Hermann BP, Castro C, Simerly C,<br />

Orwig KE, Mitalipov S, Schatten G. Systems biology discoveries using<br />

non-human primate pluripotent stem and germ cells: <strong>No</strong>vel gene and<br />

genomic imprinting interactions as well as unique expression patterns.<br />

Stem Cell Res Ther. 2010 Aug 5; 1(3): 24. PMCID: PMC2941116.<br />

Blanco CL, Liang H, Joya-Galeana J, DeFronzo RA, McCurnin D, Musi<br />

N. The ontogeny of insulin signaling in the preterm baboon model.<br />

Endocrinology. 2010 May; 151(5): 1990-1997. PMCID: PMC2869258.<br />

Burket J, Gourion-Arsiquaud S, Havill LM, Baker SP, Boskey AL, van<br />

der Meulen MC. Microstructure and nanomechanical properties in<br />

osteons relate to tissue and animal age. J Biomech. 2010 <strong>No</strong>v 11.<br />

Chang TC, Liu YG, Eddy CA, Jacoby ES, Binkley PA, Brzyski RG,<br />

Schenken RS. Derivation and characterization of novel nonhuman<br />

primate embryonic stem cell lines from in vitro-fertilized baboon<br />

preimplantation embryos. Stem Cells Dev. 2010 <strong>No</strong>v 4.<br />

Kochunov P, Castro C, Davis D, Dudley D, Brewer J, Zhang Y, Kroenke<br />

CD, Purdy D, Fox PT, Simerly C, Schatten G. Mapping primary<br />

gyrogenesis during fetal development in primate brains: High-resolution<br />

in utero structural MRI of fetal brain development in pregnant baboons.<br />

Front Neurosci. 2010 May 10; 4: 20. PMCID: PMC2896074.


Kochunov P, Castro C, Davis DM, Dudley D, Wey HY, Purdy D, Fox<br />

PT, Simerly C, Schatten G. Fetal brain during a binge drinking<br />

episode: A dynamic susceptibility contrast MRI fetal brain perfusion<br />

study. Neuroreport. 2010 Jul 14; 21(10): 716-721. PMCID:<br />

PMC2898126.<br />

Rane S, Nair G, Duong TQ. DTI at long diffusion time improves fiber<br />

tracking. NMR Biomed. 2010 Jun; 23(5): 459-465. PMCID:<br />

PMC2949954.<br />

Ren C, Fan-Havard P, Schlabritz-Loutsevitch N, Ling Y, Chan KK, Liu<br />

Z. A sensitive and specific liquid chromatography/tandem mass<br />

spectrometry method for quantification of nevirapine and its five<br />

metabolites and their pharmacokinetics in baboons. Biomed<br />

Chromatogr. 2010 Jul; 24(7): 717-726.<br />

Zurcher NR, Rodriguez JS, Jenkins SL, Keenan K, Bartlett TQ,<br />

McDonald TJ, Nathanielsz PW, Nijland MJ. Performance of juvenile<br />

baboons on neuropsychological tests assessing associative learning,<br />

motivation and attention. J Neurosci Methods. 2010 May 15; 188(2):<br />

219-225.<br />

Grants Awarded to SNPRC Staff and Affiliates<br />

June 2010 – <strong>No</strong>vember 2010<br />

Brasky, Kathleen, SFBR PI: Effects of Aging on Evoked Otoacoustic<br />

Emissions in the Common Marmoset (NIH/University of <strong>Texas</strong> at San<br />

Antonio; PI: Rama Ratnam), 7-month award of $38,210<br />

Brasky, Kathleen, SFBR PI: Effects of Aging on Evoked Otoacoustic<br />

Emissions in the Common Marmoset (NIH/University of <strong>Texas</strong> at San<br />

Antonio; PI: Rama Ratnam), 6-month award of $24,227<br />

Cummins, Bill: <strong>No</strong>nhuman Primate Caging for the SNPRC (NIH), 1-year<br />

award of $474,534<br />

Rice, Karen, SFBR PI: Macrostructural and Microstructural Analysis of<br />

the Primate Corpus Callosum (NIH/Trinity University; PI: Kimberley<br />

Phillips), 3-year award of $61,157<br />

Rice, Karen , SFBR PI: Development of Hemispheric Specialization in<br />

Capuchin Monkeys (NSF/ Trinity University; PI: Kimberley Phillips),<br />

1-year award of $18,803<br />

Rice, Karen, SFBR PI: Baboon Study (Commercial), 18-month award of<br />

$14,486<br />

Shade, Robert: Feasibility of Lower Body Negative Pressure as a<br />

Hypovolemia Model in Baboons (U.S. Army), 1-year award of<br />

$191,112<br />

VandeBerg, John L.: Chagas Disease: An Emerging Fatal Disease in<br />

<strong>Texas</strong> (Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation), 1-<br />

year award of $345,751<br />

SNPRC Supplemental Awards<br />

June 2010 – <strong>No</strong>vember 2010<br />

Consortium and Translational Activities (NIH), 8-month award of<br />

$1,080,295<br />

Maintenance of NCRR-owned Chimpanzees: FY2010 (NIH), 1-year<br />

award of $547,374<br />

Renovation of SNPRC Chimpanzee Housing (Bldg. 112) (NIH), 1-year<br />

award of $1,000,000<br />

Maintenance of SNPRC Chimpanzee Cages (NIH), 1-year award of<br />

$499,995<br />

Animal Records Management System (NIH), 8-month award of $100,591

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