WPRC appoints new associate directors

Steven Knable leads Center Operations

Steve Knable, M.B.A., began Aug. 1 as Associate Director for Operational Services, to succeed Robert Watson, B.S., who plans to retire next summer after 32 years of service.

Knable brings over 25 years experience in research administration and business development within the non-profit research sector, as well as in university sponsored research. Most recently he served as Vice President for Finance at the National Opinion Research Center (NORC) at the University of Chicago.  During his term at NORC, he was instrumental in expanding annual research funding from $30 million to $55 million per year.

Knable has set two broad objectives for the Primate Center: 1) Position and restructure Operational Services to better address pending growth in research and service programs; and 2) Develop and execute an aggressive fund raising initiative to expand research infrastructure and maintain the Center’s world class research environment. Operational Services includes Financial Management, Human Resources, Data Management and Digital Imaging, Grant Administration, Purchasing, and Facilities Management.
 

Amy Usborne manages Research Services

Amy Usborne, D.V.M., Diplomate A.C.V.P., assumed the responsibilities  of Associate Director for Research Services July 1. Joseph Kemnitz, Ph.D., had been serving in this capacity since 1995.

Dr. Usborne will oversee activities in the seven service units of Pathology, Assay, Immunology, Library and Information, Reproduction Research, Stem Cell, and Virology Services. She brings new energy and fresh ideas to developing and coordinating these services.  She will focus on assisting unit heads in fufilling stated goals in the recent grant renewal, and on aiding the development of increasingly sophisticated technologies required by investigators.

Usborne will continue as head of the Pathology Services Unit, a position she assumed in 2002, succeeding James Thomson, V.M.D., Ph.D.
 

New hope for PCOS treatment, prevention

Millions of women with polycystic ovary sydrome (PCOS), a complex and dangerous  disease, may soon see better diagnosis and treatment. 

Researchers in the U.S. and United Kingdom believe they have pinned down when and how PCOS originates. Reporting in today’s issue of Journal of Endocrinology, the researchers explain how prenatal genetic, biochemical and environmental factors combine to produce PCOS later in life. The disorder affects at least 4 million women of childbearing age in the U.S. It is a common, but complex reproductive disorder and a major cause of infertility. PCOS is also the leading cause of Type 2 diabetes in women in their 20s and 30s and puts women at high risk for cancer in the uterus.  (More at www.primate.wisc.edu/WRPRC/press.html)
 

Seminar Series underway

The WPRC Fall 2002 Seminar series got off to a great start. Topics included stem cells, AIDS, Harry Harlow, and zoo veterinary medicine. Please help us make Spring just as successful! Send your suggestions, or better yet, volunteer as a speaker for the Primate Center Spring Seminar Series. We need at least one speaker per month from January through May, 2003. Also, if you are not on the Seminar Series e-mail list, please let your Centerline editor know (jlenon@primate.wisc.edu).
 

New enrichment forum

The Primate Enrichment Forum (PEF) is hosted by the Wisconsin Primate Research Center via Primate Info Net. PEF is an e-mail list devoted to discussion of social and environmental enrichment for laboratory housed primates. The list is open to people who directly care for and do research with nonhuman primates in biomedical facilities. Animal caretakers, veterinary, research, and behavioral technicians, veterinarians, research scientists, behaviorists/enrichment coordinators, and colony managers are all encouraged to apply by visiting the Primate Enrichment Forum’s new Web site at www.primate.wisc.edu/pin/pef/>www.primate.wisc.edu/pin/pef/> and clicking on the link to the application form. For more information, you may also write the list administrator, David Seelig, Ph.D.; dseelig@vet.upenn.edu>dseelig@vet.upenn.edu.
 

Hats off to our students

Thank you, Michelle, for your caretaking, preparing of snacks and toys, feeding, and daily monkey health checks. I remember you coming to us as a freshman psychology major. After your first Primates and Behavior class, you were so excited by what you learned, you marched straight down to the Primate Center and asked if you could work here. Your spirit, and that of many other students we have met over the years, is unforgettable.

Sept. 6, 2002

Dear Jordana,

I have since moved back to the East Coast to work at the international nonprofit Earth-watch.  I am a coordinator for 24 research projects in our Earth and Marine Science department. I work mainly with the volunteers (about 1,100/year) who pay a share of the research grant to work with the scientists in the field. I have become interested in marine science, but the primatology interest is still there, so Earthwatch put a chimpanzee project under my care. I am working with Roger and Debbie Fouts as well as Mary Lee Jensvold over at the Chimpanzee and Human Communication Institute at Central Washington University. We send volunteers there regularly to help with general caretaking and beha-vioral observations.

They are trying to determine the best enrichment methods for apes in captivity and the volunteers have been coming back with rave reviews. Included among the four chimps is Washoe, most famous for learning sign language and featured extensively in Roger’s book, Next of Kin. We also have a project in Sri Lanka studying temple-dwelling macaques. The projects are usually two weeks long and we often have discounts for college students. 

I wanted to check in and say hello and also give you the heads up that this kind of experience exists for anyone else who may come to you for information …I am so happy to be working here with the volunteers, the researchers, and the staff. The best perk of the job is the occasional site visit in the field. I just returned from our whale sharks project in Baja, where I gathered bio data from the sharks and collected plankton samples for two weeks in the gorgeous Bahia des Los Angeles. I feel lucky to have this position and I’m so proud to be a part of the organization.

Please give my best to everyone at the Center!

Michelle Jost
Expedition Coordinator, Earth and Marine Sciences
www.earthwatch.org
Maynard, Massachusetts
 

Gleanings

New grants

Eva Rakasz, Ph.D., Immunology Services head, has received a one-year Great Lakes Regional Center for AIDS Research (CFAR)  developmental award. The grant is titled, "IgG Fc domain containing proteins as mucosal vaccination vehicles." 

Catherine VandeVoort, Ph.D. (California National Primate Research Center), Dee Schramm, Ph.D. (WPRC), and Stanley Leibo, Ph.D. (Audubon Center for Research of Endangered Species, LA), have received a five-year NCRR grant, "Protocols for maturing and freezing monkey oocytes."

Honors

Joseph Kemnitz, Ph.D., has been elected Secretary Treasurer of the Biological Sciences Section of the Gerontological Society of America, for 2002-2005.

In the news

Robert Freedman, Ph.D., described his research on menopausal hot flushes in the New York Times Sept. 3. Freedman is a professor of psychiatry and OB/GYN at Wayne State University in Detroit and a WPRC affiliate researcher studying menopause on rhesus monkeys.

On Aug. 30, ABC News Prime Time aired the special, "Looking Younger, Living Longer: What Every Woman Wants to Know." Richard Weindruch, Ph.D., and Center monkeys appeared on the program. Weindruch and Joe Kemnitz, Ph.D., also spoke on aging and caloric restriction with Channel 27 Local News in July.

Optomen Productions from London visited David Abbott, Ph.D., and Nancy Schultz-Darken, Ph.D., July 19. The TV crew collected footage for a science documentary to air in the UK and on the National Geographic Channel addressing Dr. Nikhil Dhurandar’s research with WPRC scientists on a suspected obesity virus that affects primates. The team has used rhesus and marmosets at the Center to demonstrate that AD-36 injected into primates causes obesity.

David O’Connor, Ph.D., in the Watkins lab, is helping raise AIDS awareness in Wisconsin:
--O’Connor was a guest columnist in the Wisconsin State Journal July 21, penning, "New AIDS treatment is still no substitute for education, prevention." He appeared on Channel 27 local news the same week.
--He was featured Oct. 25 in Wisconsin Public Television's WeekEnd report on AIDS Walk participants and raising political support for fighting AIDS. O’Connor explained that, because ongoing research has revealed new roadblocks to an HIV vaccine, there is an heightened need for education and prevention, especially in young people. Teens and young adults represent the highest rate of new HIV cases in the state, yet this group has also become the most complacent about the virus. 

UW Life Sciences Communication students Charles Youngquist, Chrissy Micke, Shawn Marchand and Paul Vogelman produced the aforementioned AIDS report. In addition to O’Connor, the group was assisted at the WPRC by Deborah Barnett, Ph.D. (who is married to Youngquist). WeekEnd co-anchor Patty Loew is an assistant professor teaching video documentary production at the UW. The WeekEnd/UW partnership is supported in part by a grant from the Morgridge Center for Public Service.

AP World Politics ran a story titled, "Yeast experiments challenge scientists’ notions about aging" July 17. Rick Weindruch, Ph.D., was quoted in the story, which focused on the role antioxidant vitamins and supplements may play in the aging process. Researchers at MIT led a recent study, published in Nature, which may challenge traditional notions that free radicals play a central role in aging and longevity.
 

New staff

Business Office
Susan Baculik, payroll and benefits specialist 3, Oct. 7.

Library and Information Services
-Angela Andres, serials assistant, July 29.
-Sean Flannery, library services assistant, Sept. 19.

Pathology Services
-Sheree Beam, research associate, Sept. 3 

Virology Services
-Angela Schoolmeesters, associate research specialist, Sept. 9.
-Laura M, Schorrak, associate research specialist, June 17.

Kemnitz Lab
-Jamie Barger, Ph.D., postdoctoral trainee, Sept. 1.

Golos Lab
-Edith Breburda, D.V.M., Ph.D., research associate, Aug. 1.

Thomson Lab
-Erika Reinfried, B.S., associate research specialist, July 15.
-Kristopher Murphy, B.S., associate research specialist, Aug. 5.
-Karthik Ramachandran, project assistant, Sept. 3.

Terasawa Lab
-Erin Carmody, research assistant, Aug. 1.
-WooRam Kim, research assistant, June 17.
-Hideki Abe, research associate, Oct. 14.

Watkins Lab
-Judith Peterson, project assistant 3, Sept. 8.
-Shari Piaskowski, B.S., research specialist, July 15.
-Christi Wojewoda, B.S., assoc. research specialist, June 17.
-Levi Yant, B.A., M.A., research specialist, July 29.

Departures
-Pam Tannenbaum, Ph.D., research associate, Aug. 30. 
-Michael Wolfgang, Ph.D., research assistant, Golos lab, May 1.
 

Correction

Where in the world is Steve Shelton?

From Capitol Court to Cayo, 

Distinguished Researcher travels many roads

Steven Shelton, B.S., began studying primate behavior as a young research assistant in the late 1960s. As his research interests grew, he considered going back to school to get a Ph.D., and perhaps teach, but somewhere along the line, he got too busy.

Shelton has enjoyed a productive career studying basic stress, learning, and emotion, in everything from rats and rhesus to humans. He has collaborated with some of the most recognized scientists in the field. In fact, he has remained so dedicated and focused on research for the past 37 years that in 1998, he became the first member of UW-Madison’s academic staff to receive the title Distinguished Researcher. Then, in 2001, Shelton received the UW Chancellor’s Award for Research.

Shelton has enjoyed one of the longest running, most successful collaborations on campus, with Ned Kalin, M.D. The two have led discoveries that shed light on the mechanisms underlying adaptive and maladaptive behavior. These findings have the potential to better understand mental illnesses and to guide the development of new treatments. Their work is particularly relevant to illnesses such as depression and anxiety.

As a result of all this success, Shelton has had to "live" in many different offices and labs in at the UW.  He often finds himself shuttling among half a dozen sites—the Primate Center, the Harlow Center for Biological Psychology, the W.M. Keck Laboratory for Functional Brain Imaging and Behavior, the Medical Sciences Center, and "WISPIC", (moniker for Wisconsin Psychiatric Institute and Clinics), which houses, among other things, the HealthEmotions Research Institute, Kalin’s clinical practice and Kalin’s lab. On a recent tour of all his haunts, Shelton picked up mail from more mailboxes than any reasonable person should have to keep track of, and stopped in for staff updates at numerous offices. Kalin and Shelton either manage or collaborate with more than 100 people working in a veritable Über-lab of primate and human psychoneuroendrocine research. In addition to his research, Shelton has enjoyed mentoring students through UW’s Medical Scholars program for the past 15 years.

The Kalin/Shelton lab at the Harlow Center for Biological Psychology, next to the Primate Center, is the best place to start if you’re looking for Steve. The place was abuzz with activity on a recent visit. Students and technicians were working on a variety of projects, running questions by Shelton nonstop, and coming and going through the glass door. No wonder all the activity: Right now, Shelton, Kalin and the lab have four major NIMH grants that involve services at the Harlow Lab and Primate Center alone. (See "Center support," p. 10.) 
 

Early years

As an adventuresome and somewhat untamed 20-year-old Shelton took a so-called "side-trip" from Santa Fe, New Mexico, to Madison, Wisconsin. "I came here for a summer job and sort of parlayed it into 35 years," he said. 
Originally from West Virginia, Shelton grew up in Santa Fe and was not interested in science.
Rather he was drawn to art, literature, math and martial arts. Then, an experience working as an undergraduate in a learning and memory rodent lab at the University of New Mexico nudged him toward research. When a similar position opened at the UW, Shelton was attracted to it because of the opportunity to work with primates. He also kept busy moonlighting as a martial arts instructor. The summer experience was so rewarding that in 1969 he permanently returned to Madison.

On the fourth floor of the Primate Center, Shelton worked with John Davenport, Ph.D., then Interim Director of the Primate Center, Harry Harlow Ph.D., the originator of primate research at the UW, and Harry Waisman, for whom the Waisman Center is named. The value of primate work was apparent to him early on in his career as he was able to easily link his findings to humans. The similarities in social and emotional behavior and, importantly, brain structure between rhesus and humans made the work all the more exciting. "At the time, we were unable to do sophisticated things like brain imaging," he said. "Today, we perform similar functional imaging studies in humans and monkeys.  It is amazing to see how similar brain structure and function are between these species." 

"My coming to Wisconsin was historic and important to me," Shelton said. "There was a tremendous amount of press being attributed to Wisconsin at the time. Harlow’s behavioral work was featured in Look and Life magazines, and just about every other major magazine or scientific journal. Ironically, the first scientific journal article Shelton had ever read was Harlow’s now classic surrogate mother research. Looking back, he said, those studies had a simple elegance that profoundly changed the way our society views child rearing, mental illness, and attachment.

Shelton was involved primarily in studies by Harlow and Waisman. Another study with John Davenport examined the effect of thyroid status on monkey learning.

"At the time, the World Health Organization was concerned that malnutrition may have been creating a whole generation of mentally retarded children. These were the first studies to really look into that link. We learned that the source of protein in the diet, animal or vegetable-derived, doesn’t matter; as long as there is enough nutrition, the brain is fine. Believe or not, 40 years ago this was not obvious." 
 

A lifetime partnership

By the early ‘70s, John Davenport became gravely ill and had to leave research. Shelton partnered with, Jim Allen, D.V.M., and Bob Bowman Ph.D., to explore the effects of lead on behavior.  He then collaborated with Gary Kraemer, Ph.D., and Bill McKinney, M.D., who later became Psychiatry Department Chair.

"A young resident of Bill’s wanted to come down and learn about primate research," said Shelton. "That’s how Ned Kalin and I met. Having seen a lot of young researchers come and go, as soon as I met Ned, there was no question in my mind that he was going to go places."

When he finished his residency, Kalin headed to the NIH. After he finished his work in Bethesda, he accepted a faculty position at in the Department of Psychiatry at UW-Madison and that is when he and Shelton officially teamed up.

"We knew we would work well together," Shelton said. "We complemented each other quite well. We worked hard, but we also really enjoyed our successes." 

Their early efforts garnered many grants. "We did primate research in the morning, human research in the afternoon, and at night we ran the samples," Shelton said. "We studied corticotrophin releasing hormone (CRH), and its effect on the hypothalamic pituitary adrenal (HPA) axis, the stress response system in primates. We wanted to explore it in relation to human depression. How did the system change when people got depressed?"

CRH, a 41-amino acid peptide, in the HPA axis is the brain’s first response to a stressor. This turns on the pituitary to release ACTH, which in turn releases cortisol from the adrenal gland? the "flight-or-flight" hormone. "What happens to the HPA axis?" Shelton posed. "We knew that depressed patients had an overactive stress response and we wanted to understand the importance of this." In a now classic experiment, Shelton and Kalin administered the hormone directly into rhesus brains. The findings were dramatic and unexpected. High doses of CRH made monkeys depressed; in lower doses they became anxious. This was among the first evidence suggesting that increased CRH activity in the brain underlies depression and anxiety. Clinical research performed elsewhere revealed this was in fact the case. Today new treatments for depression and anxiety are being developed based on these early observations.
 

"Show me an emotion"

By the early 1980s, Shelton and Kalin had a couple of lab volunteers, but still did most of the work themselves. Outside their marriages, their social lives consisted of occasionally going down to Memorial Union and taking sailing lessons. "We used to say that when we were successful, we were going to go sailing every Friday," Steve remembers. "Of course, now we have many more demands, so our dream is still on hold."

Kalin is Psychiatry Department Chair and also directs the HealthEmotions Research Institute. "As chair of the Psychiatry Department, Ned has been able to build a strong bridge between Psychiatry and Psychology," Shelton praised.  Initially, the relationship was forged by Kalin and Richard Davidson, Ph.D., working closely together. "Richie is one of the most recognized experts in emotion research and has become a wonderful collaborator," Steve added. The researchers have been able to investigate issues related to normal emotion and psychopathology at clinical and preclinical mechanistic levels. 

Shelton’s and Kalin’s long-term goals are to understand the fundamental causes of abnormal emotional responses and how they predispose people to stress. Their early studies published in Science revealed that different brain chemicals regulated different aspects of stress and fear-related behavior. For example, endogenous opiate compounds modulate mother and infant attachment distress, whereas drugs like valium affect fear and anxiety. The work yielded new ideas on treating illnesses such as anxiety and depression. Other experiments involved unraveling the underlying contributions of genes and critical experiences in the development of psychopathology.

About six years ago, Kalin and Davidson established the HealthEmotions Research Institute in the Department of Psychiatry. The Institute has attracted more students to "the biology of emotion" field. Davidson also directs the Keck Brain and Behavior Imaging Laboratory. The lab houses state-of-the-art technology that makes taking detailed structural and chemical pictures of the brain possible. In addition to the full-size MRI and PET scanning machines, Kalin and Andrew Roberts, Ph.D., recently received an NIH Instrumentation grant to purchase a portable monkey PET scanner.

"This allows us to gain amazing resolution of brain areas that we could not see before," Shelton emphasized. "It is very exciting to be able to perform the same scans in monkeys as those being performed in humans. This definitely adds to the relevance of the primate studies." Shelton also collaborates with Onofre DeJesus, Ph.D., in Medical Physics. DeJesus specializes in the development of new PET radiotracers for studying Parkinson’s disease and other movement disorders, substance abuse, schizophrenia, and cancer.

PET studies involving rhesus monkeys in this campus would not have been possible without Shelton's expertise and dedication, DeJesus stated. "I remember when we first started PET imaging rhesus monkeys in the late ’80s. Because the human clinical scanner was available to us only on nights and weekends, Steve was the last one to leave around 3 or 4 a.m; he made sure that the monkeys recovered from the anesthesia. He really deserves the honors and awards bestowed on him."
 

To Cayo Santiago

Shelton’s work has extended beyond the traditional laboratory to a naturalistic setting on the Island of Cayo Santiago. Located off the coast of Puerto Rico, the isle is inhabited by approximately 1,000 free- ranging rhesus monkeys. Over the past 10 years,  Shelton and Kalin have been studying the biology and behavior of a subset of monkeys to determine the physiological makeup of individuals who are vulnerable to stress.  At least once a year, Shelton travels to the island to oversee behavioral data and biological measures collection. (His fluency in Spanish has been a great aid to his efforts.) 

"Going to Cayo Santiago became my dream after I heard about it," Shelton reflected. "When I first went down there with Ned 10 years ago, there was no real refrigeration or other necessary laboratory supplies. We established a portable lab to perform endocrine and immune studies.  A pilot grant from a private Health-Emotion’s donor allowed us to modernize our efforts."

Behaviorist Clarence R. Carpenter, Ph.D., first brought rhesus monkeys to the island in 1938 to study behavior, anatomy and tropical diseases. Today the expanded population is mostly observationally studied. "Our studies combine minimally invasive procedures with rich behavioral data to allow for a unique synthesis of behavior and biology," Shelton said. "The work at Cayo is an important complement to our laboratory studies." Recently funded by NIMH, the research is part of the Mind-Body Center grant directed by Davidson.

The Über-lab tour has reached its end. Shelton’s many haunts—through back alleys and in basements, at monkey labs and out in Madison’s Research Park—are running smoothly for another day. He has worked at the Primate Center, Harlow Lab, Psychology building, Waisman Center, VA Hospital, and wherever else his research has led him. One might argue that the only thing constant about all these places has been Steve. "Some of the animal areas are now my offices, and some of my former offices are now animal areas," he said.

He appears to be a man at peace, with a mix of self-depreci-ating humor and calm temperament, but also a spark for life. He’s always alert and on the move. Maybe its his martial arts  background. Or it’s because he gets so much exercise being everywhere at once. Or, he just loves what he does. 

 "I’ve been extremely fortunate to be involved with science advances at the UW," Steve said. "When I first came to Madison, I never imagined that I would stay... Its been 35 years and I don’t know the meaning of burnout.  There are many more important discoveries just around the corner." 
 

Center Support and Current Projects

Steve Shelton has worked at the Primate Center and Harlow Lab for 35 years. When he compares the old, small and dim surgery rooms to the WPRC’s new facilities, he gets excited.

"The new surgery suite and facilities are a tremendous asset to our work," he said. "We bought a large surgical microscope which can be housed in the new addition, so I am over at the center a lot more these days. Having been to other surgical suites throughout the United States, I can tell you the facilities are top-notch, When I walked in there, my mouth dropped open because I didn’t know it would be quite so spectacular."

Denny Mohr, who supervises Center surgical needs, has been of great help to the Kalin-Shelton lab: "Denny always has everything ready that you need, even things you didn’t know you needed. I can’t believe all the things he has to keep in mind, he’s amazing."

Shelton also acknowledges the work of Doug Cowley, Russell Vertein and the rest of the Animal Services staff. "Having ‘grown up’ with such wonderful colleagues such as Doug and Rosie for all these years has really made the primate center not only a great place to do research, but also like a family," he said, "This is an opportunity to say thanks that doesn’t come along that often."

The lab is currently involved in several projects that depend on NIH and Primate Center support. The study, "Affective style: social and psychobiological substrates," uses the rhesus monkey to characterize the behavioral and physiological correlates of extreme behavioral inhibition and investigate brain mechanisms underlying this trait.

Behavioral inhibition (BI) or, in its extreme form, freezing, is an adaptive response individuals engage in when confronted with threatening situations. Clinical research has demonstrated that excessive BI is a trait marker for very shy children who develop into overly fearful adolescents and adults.  Later on, these individuals are likely to develop clinically significant anxiety and depression. Extreme behavioral inhibition may be an early marker for psychopathology. Kalin and Shelton developed a paradigm in rhesus monkeys to assess BI.  They characterized the biological correlates of extreme BI and found that affected animals have relative right frontal electrical activity and elevated basal cortisol levels. They further characterized the endocrinology phenotype of fearful temperaments.

A second project, "Development and Regulation of Emotion," explores, through sophisticated behavioral measures, the neural system underlying the expression of emotion in primates. Results point to a key role for the amygdala in processing acutely fearful stimuli. This is highly relevant to humans, as it addresses the role of amygdala-orbitofrontal interactions in mediating normal emotion and psychopathology.

People with positive vs. negative dispositions have lower levels of stress-related hormones, better immune function, and are more likely to survive stressful social and physiological insults. In humans, social stress often leads to psychological and physical disability.  A recent study found that depression greatly increases the risk of death in people who recently suffered heart attacks.  Kalin and Shelton’s NIMH grant "Social stress in primates: Vulnerability and resilience," attempts to understand the interaction between survival and social stress, studying monkeys on Cayo Santiago.

"The Amygdala and Primate Sleep," (Ruth Benca, MD, Ph.D., principal investigator) supports preclinical studies to examine neural circuits and mechanisms underlying primate sleep. Increased daytime emotionality, anxiety and depression are associated with sleep alterations. Since the amygdala is key to emotional processing and is connected to sleep regulating regions, the team is examining the role of the amygdala in regulating the effects of stress on disrupted sleep.