The Wisconsin Regional Primate Research Center
Joseph Kemnitz to lead WRPRC into the next millenium
WRPRC Research Highlight
Wisconsin hosts 1999 Primate Center Director's Meeting
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Kemnitz becomes the fourth director of the center he has led on an interim basis since the fall of 1996. He assumes the directorship of a key University of Wisconsin-Madison research center with a staff of 133 people, an annual budget of nearly $15 million, and world-renowned programs of research in developmental and reproductive biology, AIDS, aging and immunogenetics, among others.
Previously, Kemnitz served as a senior scientist and associate director of the center, having joined the WRPRC staff in 1976 as a research associate. In addition, he holds an appointment as a professor of physiology in the UW-Madison Medical School.
In naming Kemnitz to lead one of UW-Madison’s largest and most visible laboratories, Graduate School Dean Virginia Hinshaw said Kemnitz possesses a combination of dedication, proven leadership skills and a thorough knowledge of the center’s research potential.
“There are only eight primate centers in the United States and such centers are viewed as national research resources,” Hinshaw said. “They meet a critical need for research on diseases which impact our nation and world. Directing such a center requires strong dedication, broad knowledge and the ability to work with many different people—all skills that Joe Kemnitz certainly has.”
Supported primarily by the National Institutes of Health through an annual base grant of $4.5 million, the WRPRC is one of eight such centers nationwide. It houses nearly 1,200 primates of two species, rhesus macaques and common marmosets, and serves as a core research facility for scientists from UW-Madison and elsewhere.
Kemnitz, with three degrees from UW-Madison, including a doctorate in physiological psychology, is an expert on eating behavior, obesity and its effects on blood sugar; and the relationship between reproductive function and energy regulation. Currently, Kemnitz studies the influence of restricted but healthy diets on metabolism and aging, a line of research that he has been involved with for more than a decade.
As an administrator, Kemnitz directed the WRPRC through one of its most difficult periods when the center, under intense public scrutiny, moved some of its primates from an aging facility at the Vilas Park Zoo to the Tulane Regional Primate Research Center and the Wild Animal Orphanage in San Antonio, Texas.
But during the same period Kemnitz helped the center grow and garnered funding for a major building addition, which is nearly completed. Under his direction, the center’s research programs have expanded. Its core programs have continued to grow and support the many scientists who use the center. More than 200 scientists from UW-Madison and around the world conduct research there.
Kemnitz said his top priority will be to extend the WRPRC record of first-rate biomedical research and studies of basic primate biology. This entails attracting outstanding scientists and maintaining an integrated, multidisciplinary program that efficiently utilizes available facilities and resources,” he said.
Kemnitz said that we now live in a golden age of biology and biomedicine, and numerous critical advances in our understanding evolve from research with nonhuman primates. He cited watershed studies of embryonic stem cells, cells with the potential to grow into any tissue in the body, as one key example. That work in humans, Kemnitz noted, was predicated on and made possible by primate studies conducted at the WRPRC.
“We are also learning about the biology of aging, the genetics of the
immune system, vaccines, and about the complex interactions of brain function,
experience and behavior. These are examples of current strengths in our
program that must be maintained.”
The procedures are laborious, and there’s no guarantee the pregnancies will be successful. However, over time, this new colony will enable more controlled SIV vaccine research at the WRPRC, according to lead investigators Dee Schramm, Ph.D., and David Watkins, Ph.D.
The work is being conducted by members of the Reproduction and Development
Research Group, Reproduction Research Services Group and Immunogenetics
Development Group. Several pregnancies are underway, with the first birth
occurring Sept. 22, 1999, via C-Section.
Poccia F, Malkovsky M, Pollak A, Colizzi V, Sireci G, Salerno A, Dieli F. 1999. In vivo gamma delta T cell priming to mycobacterial antigens by primary mycobacterium tuberculosis infection and exposure to nonpeptidic ligands. Mol Med. Jul;5(7):471-6.
Background: The recognition of phosphorylated nonpeptidic microbial
metabolites by Vgamma9Vdelta2 T cells does not appear to require the presence
of MHC molecules or antigen processing, permitting rapid responses against
microbial pathogens. These may constitute an important area of natural
anti-infectious immunity. To provide evidence of their involvement in immune
reactivities against mycobacteria, we measured the responsiveness of peripheral
blood Vgamma9Vdelta2 T cells in children with primary Mycobacterium tuberculosis
(MTB) infections. Materials and Methods: Peripheral blood mononuclear cells
from 22 children with MTB infections and 16 positivity of tuberculin (PPD)-negative
healthy children were exposed to nonpeptidic antigens in vitro and the
reactivity of the Vgamma9Vdelta2 T cell subset with these antigens was
determined using proliferation and cytokine assays. Also, responses of
gammadelta T cells from rhesus monkeys stimulated with phosphoantigens
in vivo were measured. Results: The Vgamma9Vdelta2 T cell responses were
highly increased in infected children in comparison with age-matched controls.
This augmented Vgamma9Vdelta2 T cell reactivity subsided after successful
antibiotic chemotherapy, suggesting that persistent exposure to mycobacterial
antigens is required for the maintenance of gammadelta T cell activation
in vivo. The in vivo reactivity of Vgamma9Vdelta2 T cells to phosphoantigens
was also analyzed in a rhesus monkey model system. Intravenous injections
of phosphoantigens induced an activated state of simian Vgamma9Vdelta2
T cells which decreased after 2 months, i.e., with a time course similar
to that seen in MTB-infected children.
Ver Hoeve JN, Danilov YP, Kim CB, Spear PD. 1999. VEP and PERG acuity
in anesthetized young adult rhesus
This study used the swept spatial-frequency method to compare retinal
and cortical acuity in anesthetized young adult rhesus monkeys. Visual
evoked potentials (VEPs) and attern electroretinographic responses (PERGs)
were recorded from 25 monkeys (age range: 4-12 years) anesthetized with
a continuous infusion of propofol. The stimuli were temporally countermodulated
sine-wave gratings that increased in spatial frequency within a 10.24-s
period. All animals were refracted using acuity estimated from the zero
micro-volt intercept of the linear regression of evoked potential amplitude
on spatial frequency. Average sweep acuities were 23.7 cycles/deg +/- 1.5
S.E.M. and 23.1 cycles/deg +/- 1.8 S.E.M. for the PERG and VEP, respectively.
VEP and PERG acuities were within the range expected based on acuities
estimated from behavioral studies in macaques. PERG and VEP acuities were
highly correlated (r = 0.90) and equally sensitive to spherical blur. On
a subset of animals, test-retest reliability of animals, and interocular
correlations, were high (r = 0.87 and r = 0.83, respectively). Increasing
propofol dosage 8-fold did not degrade PERG or VEP acuity. This study demonstrates
that high spatial-frequency acuities can be rapidly obtained from young
adult rhesus monkeys under a wide dose range of propofol anesthesia using
the swept spatial-frequency method.
Lee CM, Lopez ME, Weindruch R, Aiken JM. 1998. Association of age-related mitochondrial abnormalities with skeletal muscle fiber atrophy. Free Radic Biol Med. Nov 15;25(8):964-72.
The hypothesis that mitochondrial dysfunction contributes to the senescent
loss of skeletal muscle was investigated in quadriceps from 2- to 39-year
old rhesus monkeys. Histological approaches, both cross-sectional (a single
cross-section of the muscle) and longitudinal (multiple cross-sections
of individual fibers spanning a 350-1600 microm region), were used to identify
muscle fibers with abnormal mitochondrial electron transport system (ETS)
enzyme activities and mitochondrial DNA deletions. Fibers were examined
for two ETS activities, succinate dehydrogenase (SDH, ETS complex II) and
cytochrome c oxidase (COX, ETS complex IV). The number of individual fibers
containing ETS abnormalities (predominately negative for cytochrome c oxidase
Daniel A. Dumesic M.D. (Mayo Clinic), David H. Abbott, Ph.D., and R. Dee Schramm, Ph.D., received a two-year, $225,908 NIH grant to study oocyte competency in prenatally androgenized monkeys.
Gary W. Kraemer, Ph.D., David Abbott, Ph.D., Chris Price, (ETH, Zurich, Switzerland), and Alison S. Fleming, (University of Toronto), received a $740,000 NIH grant to study the effects of juvenile experience on maternal psychobiology in marmosets.
David Abbott, Ph.D., Daniel Dumesic, M.D., Vasantha Padmanabhan, Ph.D., Joseph Kemnitz, Ph.D., and Joel Eisner received a $1 million, five-year NIH grant to study the androgenized female rhesus monkey as a model for polycystic ovarian syndrome.
Rick Weindruch, Ph.D., and colleagues’ decade-long study of how diet affects the process of growing old is expanding through a $6.75 million grant renewal from the National Institutes of Health (NIH).
Joel Eisner, a graduate student working with David Abbott, Ph.D., received a Vilas Professional Development Fellowship from the UW-Madison Graduate School.
Joan Scheffler, head of Clinical Pathology Services, has been named a recipient of the American Society for Clinical Laboratory Science’s (ASCLS) Keys to the Future award. The award is given to members who have recently increased their leadership roles in the ASCLS.
Polani B. Seshagiri, Ph.D., WRPRC affiliate, Reproduction and Development Group, was appointed associate professor April 28 at the Indian Institute of Science, Department of Molecular Reproduction, Development and Genetics, in Bangalore, India.
Igor I. Slukvin M.D., Ph.D., began a residency in pathology at UW Hospital and Clinics on July 1, 1999.
LaureLee Luchansky, senior research specialist in Dr. Ei Terasawa’s lab, departed June 16 after 9 1/2 years at the Primate Center. She, her husband John, and their four children now live in Philadelphia, where John has accepted a position at the USDA.
Marta Dykhuizen Shore of the Immunology and Virology Core moved to Minneapolis with her husband Sean June 25, after working 3 1/2 years as a research specialist in the Immunology and Virology Core Lab. Shore is now working in the AIDS research lab of Dr. Ashley Haase at the University of Minnesota.
Joel Eisner, research assistant working with Drs. David Abbott and Dan Dumesic, was hired this August as a clinical research scientist by INSMED Pharmaceuticals in Richmond, Virginia. Eisner is setting up the phase III clinical trials for the first FDA-approved drug to treat polycystic ovarian syndrome (PCOS). He expects to earn his Ph.D. in endocrinology and reproductive physiology by the end of the year.
David Fernandez, Ph.D., a postdoctoral research fellow in Dr. Terasawa’s lab since November, 1997, assumed an assistant professor’s position in the Department of Animal and Veterinary Sciences at the California State Polytechnic University, Pomona, California, Aug. 1.
In the news
Ned Kalin, M.D., and Steve Shelton were featured for their research on the Cayo Santiago rhesus monkeys in the May Discovery Channel program “Why Dogs Smile and Chimpanzees Cry.”
Toni Ziegler, Ph.D., and the cottontop tamarins on campus were featured in the recently aired Dutch-produced program “Noorderlicht” (Northern Lights) in a segment titled “Vaderliefde” (fatherly love). A copy of this 25-minute program, produced for English-speaking audiences, is available via the Primate Center Library.
In the Aug. 27 issue of Science, and reported in the New York Times, USA Today and other media, Rick Weindruch, Ph.D., Tomas Prolla, Ph.D., and colleagues described their measurement of differential gene expression in mice as a function of aging. They also identified genes from which age-related changes were mitigated by dieting restrictions, an intervention known to slow aging and extend lifespan in rodents.
Paul Kaufman, M.D., and colleagues were featured in a Wisconsin State Journal article, “Racing the age clock—UW researchers set their sights on slowing down eye diseases” May 6. Dr. Kaufman described ethnic groups at risk for glaucoma, and the difficulty in diagnosing and treating the disease, especially as the population ages and more people are affected. He and other UW physicians are advancing new drugs and surgeries to treat glaucoma. Researchers at UW and elsewhere are also looking to gene therapy research to ultimately develop a cure.
David Abbott, Ph.D., and the center’s new marmoset triplets, were covered in the Wisconsin State Journal by science writer Ron Seeley on May 13. (See http://www.primate.wisc.edu/WRPRC/triplets.html.) The marmosets also appeared locally on WMTV Channel 15.
The WRPRC has agreed to house the Marth J. Galante Conservation Award of the International Primatological Society. The award and its endowment fund, created by John C. Galante to honor his wife, provides funds for training conservation personnel from countries with native nonhuman primate populations.
In addition to housing the Galante award, the WRPRC has agreed to host the IPS’s World Wide Web site and be the repository for its organizational archives. In return, the IPS is helping support the development of the International Directory of Primatology and the World Directory of Primatologists, available through Primate Info Net at www.primate.wisc.edu/pin.
Representatives from seven Regional Primate Research Centers (RPRCs) and the National Institutes of Health gathered at the WRPRC to discuss expanding facilities, growing AIDS research programs, library and information services, Herpes B policy, and the review of the Primate Centers Program.
Highlights included Program Director Dr. Jerry Robinson announcing that the Southwest Foundation for Biomedical Research has been named the eighth RPRC.
At dinner following the meeting, Drs. Peter Gerone and Leo Whitehair were honored. Dr. Gerone will soon retire as director of the Tulane RPRC and Dr. Whitehair is scaling back his responsibilities at NCRR.
During the meeting, Dr. Joseph Kemnitz, Wisconsin RPRC director, described his center’s nearly completed 18,500 sq. ft. building addition that will serve all animal-related functions at the center. The addition will include increased animal holding space and much improved surgery and pathology facilitites. Researchers will be able to bring animals housed elsewhere on campus back to the center. “This will be enormously helpful,” he said.
Kemnitz said the center’s aging and dietary restriction studies, stem cell biology program, and MHC-typing work have been very successful. He also addressed center research into the neuroendocrinology of puberty, and an initiative to study mechanisms of menopause. Kemnitz cited Dr. Paul Kaufman’s “stellar work in presbyopia and glaucoma,” and a new grant for further PCOS studies as a followup to studies by Dr. Robert Goy in the 1970s.
“David Abbott has identified the rhesus monkey as an outstanding model for PCOS—a model which shows elevated androgens, insulin resistance, elevated body fat, and other characteristics,” Kemnitz said. Abbott is collaborating with Dr. Dan Dumesic at the Mayo Clinic.
The major challenge addressed during the meeting is the increased planning and direction needed as the primate centers put more emphasis on service and resource development in base grant funding. “We need to give scientists the up-front ability to develop their resources,” said Robert Watson, WRPRC associate director.
“Biotech companies are increasingly using our resources,” attested Dr. Gerone. “A week doesn’t go by when we don’t get new requests for using animals for research.”
Thomas Insel, Yerkes RPRC director, gave several resource updates from
his center, including new core resources such as a genomics core, tetramere
core, and viral vector core. Yet he stressed that Yerkes’ focus is
still around discoveries.
Jeff Roberts, assistant director for Primate Services at the California RPRC, emphasized, along with others, the need for pilot research projects to remain in the base grant. He also stressed more education on genetics, Herpes B, improved TB diagnosis, biobehavioral characterization, and reproductive manipulation. “Investigators meet with us to learn about our operations before they get an animal,” he explained. “They are learning more about our service cores so they know how best to use our resources.”
In other updates, Bill Morton, Washington RPRC director, described his
center's expanding and renovated breeding resources and colonies of baboons,
SIV-free macaques and Herpes B-free macaques. Jay Castle, vice president
of Administration at the Oregon RPRC, presented research updates
on aging, gene therapy, and the increased requests for investigator Don
Wolf’s embryonic transfer expertise.
Nancy Nadon, director of National Institutes on Aging Resource Development, spoke on how Primate Center directors can best help the NIA develop its highly valuable aging primates resource. She said there is a high demand for descriptive research, but researchers are increasingly asking if they can use older NIA-supported animals to test interventions.
Dr. Jerry Robinson mentioned that each RPRC is getting some young rhesus monkeys from South Carolina’s Morgan Island, to contribute to their breeding programs. “There are 4,500 monkeys on that island—it’s a national resource,” he said.
Later in the meeting, Larry Jacobsen, chief of Library Services, gave
a slide presentation on the many ways the WRPRC Library serves the global
primate research community. David Watkins, Ph.D., presented his findings
on the importance of cytotoxic T-cells in SIV/HIV vaccine development.
Christine O’Rourke, D.V.M., chief of Veterinary Services (through May 1999)
discussed revised Herpes B policy.
— Center scientists published 308 papers, abstracts,
Not only are surviving triplets rare in common marmosets, but both these sets have the same parents, a first-time achievement in captivity as far as researchers know.
The entire Primate Center staff has been watching this unique family grow, since it also happens to be our “display family.” The marmosets are housed in a glass enclosure that’s been available for staff and visitor viewing of this highly social species since the mid 1990s.
When “Dad and Mum,” as David Abbott, Ph.D., calls them, moved into the enclosure last year, they had one surviving son from their first set of infants. (Two other infants died after their mother developed mastitis.) Yet, with a little more luck and a lot more experience the second, and then the third time around, this nine-member family is now thriving.
The marmosets can teach us a good deal about primate parenting. In fact, Gary W. Kraemer, Ph.D., and colleagues have a new grant to study the effects of juvenile experience on maternal psychobiology in marmosets. (See Gleanings this issue.) They aim to learn about the involvement of specific hormones in encouraging normal—or in this case, outstanding—parental behavior. They will also examine how older siblings’ experience observing and carrying their infant brothers and sisters appears to mold them into better-than-average parents themselves.
“Without other youngsters around,” Abbott said, “the risk of a juvenile growing up to be a bad parent is much higher.”
For a primate mom to manage seven children is no small feat. At least this mom’s first set of triplets are all, literally, off her back. And no need to worry about pregnant teens either. Alpha female marmosets, who give birth every five or six months, manage to keep their daughters from ovulating or mating. Wendy Saltzman, Ph.D., Nancy Schultz-Darken, Ph.D., Pamela Tannenbaum, Ph.D., and Dr. Abbott are uncovering the mechanisms of hormonal and behavioral suppression in socially subordinate females.
In their spacious enclosure at the WRPRC, the marmosets scamper atop, rest on, hang from and gouge holes into large tree branches, much as they would in the wild. Only in this case, the branches are replaced with fresh ones every few months. And, fortunately for this super-mom, the family that plays together rests together. By late afternoon, the whole group is usually in the nest box catching up on some Z’s.
The WRPRC houses about 250 common marmosets. The species is native to
the forests of northeast Brazil. Researchers are studying them to learn
more about everything from parenting and behavior to assisted reproduction,
osteoporosis, and contraception.
In this photo, Kenyan patas monkeys studied by Anne Carlson, a zoology graduate student working with Toni Ziegler, Ph.D., and Charles Snowdon, Ph.D., demonstrate this poorly understood behavior.
A two-year-old juvenile has just snatched a two-week old infant from its mother and tries to carry it away as another, younger juvenile tries to seize the baby from its present abductor.
“These kidnappings occur constantly,” says Carlson, “and the mothers do not even attempt to get their babies back until they are either dropped on the ground, or manage to crawl away, usually after some extremely rough handling.”
No one knows for certain why this occurs, she says. “Some people think the juveniles are playing with the babies; others think they’re practicing to be parents, but not doing a very good job.”
Carlson spent 16 months in Kenya, returning to Madison last December.
She spent much of 1999 analyzing patas fecal samples at the Primate Center
to further understand the relationships among hormones, reproduction and
Jordana Lenon, Editor
Wisconsin Regional Primate Research Center
1220 Capitol Court
Madison, WI 53715-1299
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