Centerline Spring/Summer 2006

Fall meeting highlights new affiliates' work

Visual leaps and movement disorders

Saccades [suh-kahds'] or saccadic eye movements are rapid jumps from one eye position to another. The velocity of a saccade can be as high as 1,000 degrees per second. To make a saccade, pick two objects at some distance from each other and look first at one then at the other. Easy, right? Now ask a monkey to do it. Not so easy.

That doesn't stop Michele Basso from studying saccades in both humans and rhesus monkeys. Basso, an assistant professor of physiology, devotes much of her time to understanding how the brain successfully makes these visual leaps. If Basso can exact these steps, she'll better understand what can go wrong and how to intervene when a person with a movement disorder such as Parkinson's disease cannot make a simple saccade.

Basso's research on how the brain controls voluntary movement was one of five new projects using Primate Center resources highlighted during the WNPRC's External Advisory Board meeting Oct. 3-5. Because damage to certain brain regions produces profound clinical disorders such as Parkinson's disease, dystonia and Huntington's disease, Basso studies eye movements of both healthy and diseased human and monkey subjects. Since patients have deficits in movements of the body and the eyes, Basso can use eye movements as a model to study complex neural processes related to cognition and involved in producing the debilitating effects of these disorders.

The processes leading up to movements include target selection, learning, memory, planning, and expectation. To study them, Basso first records the electrical activity of single neurons while her subjects perform various eye movement tasks. In addition to recording the neural bursts of activity, she can activate or deactivate particular regions of the brain. To record both the neural bursts and the switching on or off of the involved brain regions, Basso manipulates microelectrodes temporarily implanted into the brain. Basso notes that this is not painful, and the same procedures are used in humans undergoing treatment for Parkinson's disease. This treatment, known as Deep Brain Stimulation, or DBS, is a new area of science and medicine that is yielding promising results in the treatment of various diseases.

The only difference between her two subject species is that the monkeys need more advanced training to learn how to sit still and play the required video games. Positive reinforcement for the monkeys includes a " sip for a leap"- that is, a sip of juice for each successful saccade.

Basso and her team are optimistic about future treatments for debilitating movement disorders. "The importance of the monkey's contributions to this field of research cannot be underestimated," she says.

References:

Li X, Kim B, Basso MA. Transient pauses in delay-period activity of superior colliculus neurons. J Neurophysiol. Epub ahead of print, Jan 4, 2006.

Li X and Basso MA. Competitive stimulus interactions within single response fields of superior colliculus neurons. J Neuroscience. 2005 25(49):11357-11373.

Basso MA, Pokorny JJ, Liu P. Activity of substantia nigra pars reticulata neurons during smooth pursuit eye movements in monkeys. Eur J Neurosci. 2005 Jul;22(2):448-64.

Mauritian monkeys aid genetic research

Five-hundred years ago, a band of cynomolgus monkeys-most likely one female and a few males-jumped ship and landed on the tiny island of Mauritius off the coast of Indonesia.

Primatologists have long known that the resulting colony of cynos, or crab-eating macaques, must be one of the most genetically homologous primate colonies on earth. Now technology and biomedical need has caught up with these monkeys: Researchers finally have the high-tech tools they need to characterize the genetics of these descendents. One such study involves challenging the primates with the virus that causes AIDS and then following viral progress and challenges in the animals. Since the monkeys are genetically identical, other experimental parameters can be manipulated to see which vaccine approaches are most effective.

The Primate Center purchased six of these Mauritian monkeys last summer for David O'Connor, assistant professor of pathology and laboratory medicine. He's excited about the possibilities for studying the pathogenetics of AIDS infection.

"The Primate Center staff's expertise in nonhuman primate modeling gives us a huge advantage when performing AIDS research," O'Connor says. "I can't overstate the importance of my lab's relationship with the center. We can do so many things-we can control the virus strains we use, the doses, the route of challenge. The Primate Center Library is also absolutely instrumental in answering my many questions about the monkeys we are using, such as their origins, history and genetics."

Host genetics profoundly influence viral success, O'Connor explains. Other genetic polymorphisms, such as those in alleles of major histocompatibility complex (MHC) class I molecules, do not prevent HIV infection, but instead play a role in controlling the virus in infected individuals. Although almost all preclinical HIV vaccine trials are performed with nonhuman primates, the scarcity of genetically matched populations of vaccinees make this work especially difficult.

O'Connor's team recently confirmed the relative homogeneity of his animals by identifying several MHC class I alleles that are found in more than 50% of the total island population.

"As additional host genetic factors that influence SIV and HIV disease progression are discovered, the value of Mauritian origin cynomolgus macaques will become apparent," he says. "In anticipation, we are developing the resources necessary to perform comprehensive studies of SIV pathogenesis in these animals." O'Connor adds that the cynos he acquired are all Herpes B negative, a big plus when doing infectious disease research with macaques.

O'Connor has worked at the UW-Madison in AIDS vaccine research and immunogenetics for eight years, first as a graduate student and later as a scientist in the Primate Center lab of David Watkins. O'Connor became an assistant professor in March, 2005 and affiliate scientist of the Primate Center in August, 2005. Even with his new responsibilities as a principal investigator, he remains active in AIDS education and patient care improvement initiatives. He participates in monthly videoconferences with Wisconsin physicians who treat HIV as well as other educational projects in conjunction with the Midwest AIDS Training and Education Center. (MATEC).

"My lab's overarching philosophy is simple: to contribute meaningfully to the global response to HIV," he says. "I feel very fortunate to have the opportunity to run my own lab and work with a talented and capable staff both in my lab and at the Primate Center in pursuit of this goal." (More information at: http://labs.pathology.wisc.edu/oconnor/)

References

Krebs KC, Jin Z, Rudersdorf R, Hughes AL, O'Connor DH. Unusually high frequency MHC class I alleles in Mauritian origin cynomolgus macaques. J Immunol. Oct 15;175(8):5230-9. 2005.

Smith, M. Z., C. J. Dale, R. De Rose, I. Stratov, C. S. Fernandez, A. G. Brooks, J. Weinfurter, K. Krebs, C. Riek, D. I. Watkins, D. H. O'Connor, and S. J. Kent. Analysis of pigtail macaque major histocompatibility complex class I molecules presenting immunodominant simian immunodeficiency virus epitopes. J Virol 79:684. 2005.

Preclinical model will aid kidney transplants

Rather than continuing to see his organ transplant patients gamble with taking anti-rejection medications throughout their entire lives, Stuart Knechtle envisions a better way.

As a professor of transplant surgery with the School of Medicine and Public Health, Knechtle has been doing human kidney transplants for 20 years. He has always conducted monkey studies in tandem, to test new theories of organ acceptance and rejection. Until now, he has housed his own animals through the Medical School. Last year, Knechtle moved his research program to the Primate Center and is excited about working with the Animal Care and Research Services teams.

"Our overall goal is to develop a nonhuman primate kidney transplant model to promote tolerance of mismatched organs and cells using new strategies," he details. "Organ transplantation in humans has achieved a considerable degree of success over the past 30 years, primarily through technical improvements and the development of better immunosuppressive drugs. Nevertheless, there is still room for improvement."

"Patients pay a substantial price for chronic immunosuppression," he continues. "People suffer from toxic side effects from the individual drugs, infections and malignancy." About 4 to 6 percent of organ transplants are lost annually due to rejection despite these drugs, he says.

Chemokine blockade is a new immunosuppressive strategy that Knechtle is testing on both rodent and monkey models to try and better the odds. Given after the transplant, the drugs inhibit immunologic responsiveness to an organ transplant.

Knechtle needs to use the monkeys to define the exact mechanism of tolerance induced by new strategies. Specifically, he seeks to define the degree of T-cell depletion required to produce tolerance, the role of the thymus in this phenomenon, the impact of age and thymic involution on tolerance induced with anti-CD3 immunotoxin and other strategies, and the effect of such treatment on the entire immune repertoire of treated recipients. Relevant preclinical data would permit phase I and II clinical trials in organ transplant recipients.

Knechtle is certified by the American Board of Surgery. He performs liver, pancreas, and kidney transplants, as well as hepatobiliary surgery and portosystemic shunt surgery. He is the director of liver transplantation and transplant clinical trials at the University of Wisconsin: http://www.surgery.wisc.edu/transplant/faculty/knechtle.shtml

References:

Bloom DD, Hu H, Fechner JH, Knechtle SJ. T-lymphocyte alloresponses of Campath-1H-treated kidney transplant patients. Transplantation. 2006 Jan 15;81(1):81-7.

Knechtle SJ. Development of tolerogenic strategies in the clinic. Philos Trans R Soc Lond B Biol Sci. 2005 Sep 29;360(1461):1739-46. Review.

Torrealba JR, Colburn M, Golner S, Chang Z, Scheunemann T, Fechner JH, Roenneburg D, Hu H, Alam T, Kim HT, Kanmaz T, Oberley T, Knechtle SJ, Hamawy MM. Selenium-binding protein-1 in smooth muscle cells is downregulated in a rhesus monkey model of chronic allograft nephropathy. Am J Transplant. Jan;5(1):58-67. 2005.

Torrealba JR, Katayama M, Fechner JH Jr, Jankowska-Gan E, Kusaka S, Xu Q, Schultz JM, Oberley TD, Hu H, Hamawy MM, Jonker M, Wubben J, Doxiadis G, Bontrop R, Burlingham WJ, Knechtle SJ. Metastable tolerance to rhesus monkey renal transplants is correlated with allograft TGF-beta 1+CD4+ T regulatory cell infiltrates. J Immunol. May 1;172(9):5753-64. 2004.

Directing stem cell research

Since the announcement last October that the National Institutes of Health will establish the first ever national stem cell bank at the University of Wisconsin-Madison, scientists here have been very busy. No doubt, $16 million will fund more facilities, researchers, and lab and animal models. The focus these days is on moving from basic science to clinically relevant models, meaning lab dish cultures to test ES-derived heart, brain and other cells for a better idea of safety and efficacy before animal trials. Also paramount is work involving nonhuman primates for transplant studies. Without the monkeys, there will likely be no human embryonic stem cell derived therapies, or they will take much longer to realize.

Clive Svendsen, director of the Waisman Center's stem cell program, also professor of anatomy and neurology, knows this well. He's been conducting stem cell research in Wisconsin for the past five years. He left Cambridge, UK, for what he saw as greater research efficiency and possibilities in Wisconsin, despite the state's often challenging political climate.

"In the UK, you can legally conduct embryonic stem cell research, you just have to go through a lot of red tape to do it," Svendsen said. "In the USA, and here in Wisconsin, the politics are complicated. But the motivation is very high, and we have incredible resources and people, including of course the Primate Center, which was a major attraction for me to move to the UW-Madison."

Svendsen is developing neural stem cell lines that have been modified to produce powerful growth factors. These have then been transplanted into the primate brain, in close collaboration with Marina Emborg at the Primate Center, to establish possible functional effects of this technology. Through collaborations with Su-Chun Zhang at the Waisman Center, the same GDNF secreting cells will also be combined with primate ES cell lines and directed into dopamine neurons.

The monkey component of this stem cell work will help provide essential data required before these cells can be used in clinical trials.

Svendsen sums up his research goals as three basic questions: "One, how can we prevent cell rejection? Even if we transplant cells, will they be accepted, and integrate, into the heart, brain or elsewhere? Two, will they repair or reverse damage? And three, are they safe? Can we prevent them from forming teratomas and growing out of control?"

References:

Kelly CM, Tyers P, Borg MT, Svendsen CN, Dunnett SB, Rosser AE. EGF and FGF-2 responsiveness of rat and mouse neural precursors derived from the embryonic CNS. Brain Res Bull. 2005 Dec 15;68(1-2):83-94.

Caldwell MA, He X, Svendsen CN. 5-Bromo-2'-deoxyuridine is selectively toxic to neuronal precursors in vitro. Eur J Neurosci. 2005 Dec;22(11):2965-70.

Klein SM, Behrstock S, McHugh J, Hoffmann K, Wallace K, Suzuki M, Aebischer P, Svendsen CN. GDNF delivery using human neural progenitor cells in a rat model of ALS. Hum Gene Ther. 2005 Apr;16(4):509-21.

Klein S, Svendsen CN. Stem cells in the injured spinal cord: reducing the pain and increasing the gain. Nat Neurosci. 2005 Mar;8(3):259-60.

Li J, Spletter ML, Johnson DA, Wright LS, Svendsen CN, Johnson JA. Rotenone-induced caspase 9/3-independent and -dependent cell death in undifferentiated and differentiated human neural stem cells. J Neurochem. 2005 Feb;92(3):462-76.

Calorically restricted monkeys are now senior citizens

By Alyssa Kohler, editorial assistant

The famous "CR" monkeys are showing no signs of slowing down. These are the new findings of "Project 2," courtesy of the very large National Institutes on Aging calorie restriction and aging Program Project grant that earned its third successful five-year renewal last summer under the leadership of Richard Weindruch, professor of medicine, geriatrics and gerontology, and an investigator with the geriatric research, education and clinical center (GRECC) at the VA Hospital in Madison.

Led by Dale Schoeller, professor of nutritional sciences, and managed by Ricki Colman, WNPRC associate scientist, Project 2 continues to follow 18 of the original 30 rhesus monkeys from the famous 1989 experiment as they leave their middle-aged years behind them.

"The oldest group of monkeys are now about 25, being equivalent to 60 year-old humans." Schoeller said.

So just how well are these CR monkeys aging compared to their control group counterparts? According to Schoeller, exceedingly well. The CR monkeys are showing no obesity, better blood glucose control and, based on studies from the other projects in the program project grant, fewer cellular defects and less muscular atrophy.

"In our most recent studies, we have focused on how aging affects energy metabolism. We have found that the CR animals are slowing down with age, but only a little, and no more than the calorically unrestricted monkeys." The CR monkeys show about a 2% decrease in energy expediture per year, Schoeller quantified. He added that almost all of this is due to less energy expended during physical activity. "We were a little surprised by these results, as we expected the CR monkeys to retain roughly the same energy expenditure rates from year to year, not to decrease their energy expenditure as much as the control monkeys with advancing chronological age."

The rate of decreasing energy expenditure is greater than that observed in humans, who show a decrease of about 0.7% per year. When one realizes that the maximal lifespan of the rhesus monkey is about one-third that of the human, however, the rates of decrease are remarkably similar. The reason for this is not clear, but it does suggest that this gradual decrease is a very consistent phenomenon of aging and not just a product of an accumulation of chronic diseases such as obesity and poorer blood glucose control. The variation between monkeys just as between humans in this effect is large. As none of the monkeys seem ready for a rocking chair yet, the research team will continue to follow these changes as the animals age further.

References:

Blanc S, Schoeller, D, Bauer D, Danielson ME, Tylavsky F, Simonsick EM, Harris TB, Kritchevsky SB, Everhart JE. Energy requirements in the eighth decade of life. Am J Clin Nutr, 79:303-310, 2004.

Blanc S, Colman R, Kemnitz J, Weindruch R, Baum S, Ramsey J, Schoeller, D. Assessment of nutritional status in rhesus monkeys: Comparison of dual-energy x-ray absorptiometry and stable isotope dilution . J Med Primitol, 34: 130-138, , 2005.

Raman A, Colman RJ, Cheng Y, Kemnitz JW, Baum ST, Weindruch R, Schoeller DA. Reference body mass index in rhesus monkeys: glucoregulatory and anthropometric predictors. J Gerontology, Series A: Biol Sci Med Sci 60: 1518-1524, 2005.

Research feature

Rhesus monkey is new model of dystonia

Parkinson's disease is widely recognized and afflicts an estimated 1.5 million people in the United States alone. A similarly debilitating neurological disorder, spasmodic torticollis dystonia, also known as cervical dystonia, affects about 1 million people. And yet, hardly anyone has heard of it.

Both movement disorders are current foci of Erwin Montgomery Jr., researcher at both the UW-Madison Medical School's Department of Neurology and at the Primate Center. Montgomery has successfully administered deep brain stimulation, or DBS, surgically to six people afflicted with Parkinson's and two with dystonia. With the DBS technique, pioneered by Montgomery, an electrode is inserted deep into a patient's brain. The patient waves a magnetic card across his or her chest to switch on a modified heart pacemaker connected to the electrode. This simple gesture activates an electrochemical process that eliminates tremors in most, but not all, patients. There are a number of different targets in the brain that can be stimulated, depending on the disorder.

"But no one knows exactly how DBS works," says Montgomery. To that end, he lays out the goals of his research: The short-term goal, he explains, is to fine-tune the tiny electrode's placement based on continued "cluster analysis", or scrutiny of small changes in positions and how they affect the patient's brain and movements. His long-term goal is to discover not just how, but why it works, opening the doors for safer, more effective ways to treat patients. (See sidebar, A closer look at DBS and dystonia)

Montgomery came to the UW-Madison from the Cleveland Clinic in 2004. He spent a year acquiring startup funding and establishing his lab at the Primate Center. Support came from the UW-Madison Graduate School, Department of Neurology in the School of Medicine and Public Health, and the NIH-NCRR-supported Wisconsin National Primate Research Center. In December 2005, Montgomery began using rhesus monkeys to fine-tune his surgical techniques and determine why DBS might work in some people who have movement disorders, but not in others.

According to 2005 research by Jankovic, Tsui and Bergeron at Baylor College of Medicine in Houston, Pacific Parkinson's Research Centre in Vancouver, and Allergan Inc in Irvine, California, respectively, the incidence of dystonia is much higher than doctors previously thought. As described in their abstract, presented at the Movement Disorder Society International Congress in March 2005, the disease is so debilitating that it warrants "a vigorous approach to identifying patients and initiating appropriate treatment."

From pain and loss, to hope and action

Whereas pain is a symptom in roughly half of all people who have Parkinson's, it is an all-encompassing and devastating reality for almost everyone who has dystonia. "Continuous spasms, twisting, pulling of the head down and over to the shoulder, burning sensations, horrific pain and pressure in the head, back and upper body" are some of the common descriptions by people who have the disorder. A video clip of a patient undergoing spasms on the ST Dystonia, Inc., website depicts what words cannot adequately describe. (http://www.spasmodictorticollis.org/)

Treatments include various oral medications for pain and other symptoms, Botox injections every three months, and surgery. However, not every treatment works for every patient, largely because the origins of the disorder in many patients remain unknown. Unlike Parkinson's, which is caused by a lack of functioning dopaminergic neurons in the substantia nigra, cervical dystonia is still diagnosed, or misdiagnosed, by its symptoms. Patients have been told they have fibromyalgia, multiple sclerosis, or mental illness, according to Howard Thiel, executive director of ST Dystonia, Inc., a national patients organization based in Mukwonago, Wisconsin. The organization raised $4,000 for Montgomery's research through a golf fundraiser last summer. Thiel also visited Montgomery at the Primate Center in November.

Thiel's ties to cervical dystonia run deep, as he himself suffered the disease's wrath for decades. He was repeatedly told that it was "all in his head." Finally, his neurologist diagnosed cervical dystonia and put him on Botox injections. Like a phoenix rising from the ashes, Thiel has moved past a broken marriage, a lost job and two suicide attempts to reclaim his life. His personal warmth, humor and spirit are apparent-if he appears a bit stiff-necked at times, it's only because there is a barely perceptible rigidity that still lingers in his head and neck, despite the Botox treatments. "I used to play handball," Thiel says. "I can't do that anymore, but I've still come a long way."

Thiel also credits the late Edward Schantz, a biochemist at the UW-Madison Food Research Institute, for his successful treatment. Schantz is credited on numerous web sites for discovering, along with Allen Scott and Eric Johnson, Type A toxin's paralytic effect on muscles. The scientists built upon the 1950s research of Vernon Brooks, a Montreal doctor who first isolated botulinium toxin. Schantz and Scott called their purified toxin Oculinum. In the late 1980s, Allergan purchased the rights to distribute Oculinum, changing its name to Botox.

"I remember visiting Ed in his lab, and there-sitting in this very old kitchen refrigerator-were two Mason jars filled with one of the most powerful toxins in the world," Thiel recounted. Thiel and Schantz became good friends; Thiel even gave the eulogy at Schantz's funeral in the summer of 2005. Schantz was 96.

What do we know about dystonia?

Whatever its cause, cervical dystonia results in abnormal neuronal activity in the basal ganglia of the brain, explains Montgomery, who heads the Movement Disorders Clinic at UW-Madison. "The basal ganglia are connected to almost every other part of the brain," he says.

He adds that the discovery of genetic abnormalities causing some forms of dystonia is very encouraging. As the functions of these genes are understood, it may be possible to develop treatments to prevent or slow the progression of dystonia-even in those patients for whom the disease's cause is unknown.

Unfortunately, much time will pass before treatments based on genetic abnormalities will help relieve the symptoms and disabilities afflicting those with advanced dystonia. "For example," explains Montgomery, "With Parkinson's, we know that just replacing the lost dopamine neurons has not been helpful to those with advanced disease. We have an obligation to develop treatments that will help those whose movement disorders are causing suffering and disability, and to do so quickly."

Furthermore, Montgomery says, the brains of patients with dystonia appear normal, unlike the obvious missing dopaminergic neurons in Parkinson's patients.

"We need animal models to try different types of microelectrodes and look at brain wave activity," Montgomery says. "Parkinson's disease research was greatly advanced with the discovery that a neurotoxin called MPTP could produce parkinsonism in laboratory animals. Parkinson's disease patients now are benefiting from research in MPTP-treated laboratory animals. Similarly, the recent development of DBS provides a great opportunity to better understand dystonia in laboratory animals and, subsequently, in people."

A Closer Look at Deep Brain Stimulation and Dystonia

By Erwin Montgomery Jr., M.D.

Deep brain stimulation is an FDA approved therapy for dystonia patients who have failed to respond to medication or botulinum toxin injection treatments. A DBS electrode is implanted in the brain's globus pallidus interna, sending constant pulses of electricity to the area. (In Parkinson's, the subthalamic nucleus is the targeted region. More at http://webcenter.health.webmd.netscape.com/content/article/2/1700_51708)

Prior to the implantation of the permanent electrodes, a temporary electrode with a microscopic tip is placed into the brain. This microelectrode records electrical impulses generated by individual neurons in the globus pallidus interna. Neurons communicate and relay instructions by pulses of electrical energy that can be recorded by the microelectrodes. In doing this, physicians and scientists can eavesdrop on the conversations among the neurons. We can see how neurons in the globus pallidus interna of dystonia patients are misbehaving. Ultimately, this technique could lead the way in reversing this abnormality, thereby restoring normal function.

DBS provides us with a unique opportunity to study what goes wrong in the brain with dystonia. Not only can we record brain wave activity through the permanent DBS electrodes, we can also correlate changes in the brain wave activity with different movements. Similarly, we can stimulate the nodes in different patterns, determining what is it about DBS that is most effective in controlling the symptoms of dystonia.

However, there are important questions about how DBS affects the basal ganglia, including the globus pallidus interna, that cannot be answered safely in humans with dystonia. To answer these questions, we must conduct experiments in laboratory animals, particularly non-human primates. In animals, we can place any number of recording and stimulating electrodes, which is not the case during human surgery. Furthermore, we can conduct these experiments over several months, which is impossible to do with humans, collecting and analyzing the data more efficiently.

For the last several years, we have been studying how neurons in the basal ganglia respond to DBS. One of our most important discoveries has forced us to re-think our old notions about how the basal ganglia works and how it might be affected in the disease. By comparing our better understanding of how a normal brain responds to DBS treatments, we will be in a better position to understand what the neuronal recordings from human dystonia patients undergoing DBS are telling us about how a dystonia brain misbehaves.

The opportunity to combine human and animal research at the University of Wisconsin-Madison provides us with great advantages. Insights gained from animal studies can be applied to humans; many of the instruments, techniques, computer programs and analyses methods developed in the animal lab also facilitate research in the human operating room and clinic. Methods for microelectrode recordings, for example, were first developed in animal laboratories, but are now being applied to human operations to make surgeries safer and more effective.

Our research focuses on what we can do for people who have dystonia now. The people suffering from this disorder are many-we want to make their lives better.

References:

Montgomery Jr EB, Gale JT. Mechanisms of deep brain stimulation: implications for physiology, pathophysiology and future therapies. 10th Annual Conference of the International FES Society Montreal, Canada. July 2005.

Montgomery EB Jr. Deep brain stimulation for hyperkinetic disorders. Neurosurg Focus 17 (1):E1, 2004.

New AIDS Lab Primate Center and UW

September was a busy month for David Watkins, professor of pathology. Watkins hosted a symposium, "HIV Vaccine Development: Challenges and Opportunities" at the UW Biotechnology Center, to mark the opening of the new University of Wisconsin AIDS Vaccine Research Laboratory on Sept. 16. Invited speakers included internationally renowned AIDS researchers Dennis Burton, Scripps Research Institute; Ronald Desrosiers, Harvard Medical School and New England Primate Research Center; Ashley Haase, University of Minnesota, and Bruce Walker, Harvard Medical School and Massachusetts General Hospital. Following the symposium was the lab's opening ceremony at UW-Madison's Research Park.

On Sept. 13, Dr. Watkins also taught his first class of "HIV: Sex, Society and Science," a new undergraduate level course in the Department of Medical Microbiology and Immunology. The course, which illustrates the key role science can play in solving one of society's greatest ills, filled quickly during registration.

Gleanings

In the news

(Full press releases appear at http://www.primate.wisc.edu)

"Diabetes drug may help treat Parkinson's disease." March 2, 2006. It's hard to spell and pronounce, but it could improve millions of people's lives. Pioglitazone (pie-o-glitta-zone) is a drug used to treat diabetes. Turns out it may also pack a punch against Parkinson's. Now it may be closer to clinical trials thanks to funding from The Michael J. Fox Foundation. In February, the foundation awarded one of 15 international Community Fast Track grants to three scientists at the University of Wisconsin-Madison.

"Like their pregnant mates, primate dads-to-be pack on pounds." Feb 1, 2006. Confirming what many have long suspected, scientists have found that male monkeys of two different species get heavier when their mates are pregnant.

"Wisconsin scientists grow two new stem cell lines in animal cell-free culture." January 1, 2006. Scientists working at the WiCell Research Institute, a private laboratory affiliated with the University of Wisconsin-Madison, have developed a precisely defined stem cell culture system free of animal cells and used it to derive two new human embryonic stem cell lines.

"Library Renamed in Honor of Lawrence Jacobsen." December 16, 2006. The Wisconsin National Primate Research Center has renamed its library in honor of Larry Jacobsen. The library will now be known as "The Lawrence Jacobsen Library."

"Psychologists glimpse biological imprint of childhood neglect." November 21, 2005. The absence of a loving caregiver in the earliest years of life could sway the normal activity of two hormones - vasopressin and oxytocin - that play an essential role in the ability to form healthy social bonds and emotional intimacy. (http://www.news.wisc.edu/11882.html)

Seth Pollak joins children at the Waisman Center's early childhood program, trailed by a film crew from NBC's Today Show. (Photo by J. Lenon.)

"WiCell receives $16 million NIH grant to create national stem cell bank." October 3, 2005. The WiCell Research Institute has been selected by the National Institute of Health (NIH) to establish the federal government's first and only National Stem Cell Bank (NSCB), it was announced today at a news conference in Madison.

"Jacobsen endows scholarship fund." October 4, 2005. Larry Jacobsen, UW alumnus and former director of the UW-Madison Primate Research Center Library and Information Services, has created a $100,000 endowment for the School of Library and Information Studies.

Awards

"Kalin receives award meant to spur advances in psychiatry." Nov. 7, 2005. Ned A. Kalin, the Hedberg Professor of Psychiatry and Psychology and chair of the department of psychiatry at the University of Wisconsin Medical School, has received the national Edward A. Strecker Award for 2005. (http://www.news.wisc.edu/releases/11820.html)

"UW primate authority elected to national academy." May 3, 2005. Karen B. Strier, a renowned primatologist and authority on Brazil's muriqui monkeys, one of the world's most threatened animals, has been elected to the National Academy of Sciences (NAS) (http://www.news.wisc.edu/11150.html)

New board members

Two new WNPRC External Advisory Board members began in 2005: Bill Morton, V.M.D., of Paris NHP and previous director of the Washington National Primate Research Center, and Marc Drezner, M.D., professor of medicine and endocrinology, UW-Madison Medical School. They join current board members Jeanne Altmann, Molly Carnes, Bill Scanlon, George Bray, Rodney Phillips, Bill Langston, Jerry Strauss, Melinda Novak, Arnold Ruoho and Tom Butler.

New grants

WNPRC senior scientist Marina Emborg, Jeffrey Johnson, associate professor of pharmacy, and Joseph Kemnitz, professor of physiology, garnered a Community Fast Track grant from the Michael J. Fox Foundation for Parkinson's research to explore the potential of furthering pioglitazone as a treatment for Parkinson's Disease.

Ted Golos, professor of Ob/Gyn, received an NIH R21 grant, "ES cell model for placental development" in August.

Psychiatry Department Chair and professor Ned Kalin joined Richard Davidson, professor of psychology and psychiatry, to garner a new grant titled, "Development and regulation of emotion in primates." Funded by the NIMH, the $2.7 million award will support the duo's work in this area for the next five years. Steven Shelton, distinguished researcher in the Psychiatry Department, will collaborate on the research.

WNPRC Library and Information Services received a five-year, $2.8 million grant renewal from NIH-NCRR titled, "Coordinated information services for primate research". The grant will allow the library staff to continue providing world-class services and resources while, at the same time, promoting the rapid sharing of information among the eight National Primate Research Centers and the larger community of primatology and biomedical researchers.

Retirements

Long-time Primate Center employees Jacque Mitchen, Steve Brice and Doug Cowley all retired within the past year. Mitchen was the Virology Core head until 1995 and the Centralized Protocol Implementation head since 2004. Both Cowley and Brice spent time as lab animal technicians, then were promoted to supervisors, Cowley in 1970 and Brice in 1979. These three were backbones upon which much of the Primate Center's research and reputation has been built. We thank them for their many years of service and wish them all the best in their retirement.

Visit to Nanning

Making the rounds of the primate facility in Nanning, China in September were, from the left: Alex Zhang, professor and director, Cell Therapy Center, Beijing Institute of Geriatrics, Capital University of Medical Sciences, Beijing, China, and head of TheraCells, Nanning, China; Theo Palmer, assistant professor of neurosurgery, Stanford University School of Medicine, Palo Alto, California; Joe Kemnitz, WNPRC Director; Tom Butler, WNRPC External Advisory Board; Ken Kubota, Los Altos, California; Buddy Capuano, associate director for Animal Services at the WNPRC.

Animal Services friends roll out the good cheer

Fifteen members of the Animal Services staff got together over two consecutive December nights to enjoy some holiday cheer and to assemble 1,200 popcorn balls for the monkeys under their care. Nearly every Old World monkey got one of the popcorn, cranberry and nut treats. In other news from Animal Services, staff celebrated International Laboratory Animal Technician Week this winter by attending the National American Association of Laboratory Animal Science (AALAS) convention in St. Louis, Missouri. On the training front, about 10 members of the division attended an English-as-a-second-language course this winter. Many had already participated in a successful, Spanish in the Workplace course last summer; both courses were coordinated with the Center's Human Resources Office. Another class, to help staff prepare for AALAS Laboratory Animal Technician exams, is also in the works. The class is a collaboration with other departments on campus, such as Laboratory Animal Resources, the Research Animal Resources Center, and the Vet School.

New Compliance, CPI leaders

Sandra Boehm is the Primate Center's new compliance coordinator in the Animal Services Division. Sandra will be responsible for helping investigators prepare and maintain research protocols involving WNPRC animals, conducting post-approval compliance monitoring, and keeping standard operating procedures up to date. Nancy Schultz-Darken former colony manager in Animal Services, is the new head of Centralized Protocol Implementation (CPI) in the Research Services Division. She succeeds Jacque Mitchen, who retired last summer.