If two renegade violins started quietly playing “Ode to Joy” during Beethoven’s “Fifth Symphony,” some audience members might sense a problem. If the errant violins increased in volume and recruited the woodwind and percussion sections, the result would just be noise. Researchers think something similar is happening when nerve cells in the brain of a Parkinson’s disease patient begin to exhibit abnormal firing patterns.

“There is a symphony of activity going on in the brain all the time,” says Dr. Marjorie Anderson, professor and vice chair of rehabilitation medicine and professor of physiology and biophysics. “In Parkinson’s patients, the normal activity of nerve cells is interrupted.”

The nerve cells are actually responding to a deficit in the neurotransmitter dopamine. The results are the debilitating symptoms of Parkinson’s, including chronic muscle tremors, rigidity, poor balance, and difficulties walking and coordinating movements. At least 1 million people have Parkinson’s disease, including Pope John Paul II and actor Michael J. Fox. At least half of these people may be undiagnosed, because the symptoms usually appear after a patient turns 50.

“There’s a lot of evidence to suggest that some people are susceptible to environmental factors,” says Anderson. “And that, in conjunction with genetic predisposition to toxins, may trigger the onset of Parkinson’s symptoms.”

Anderson’s career has focused on the globus pallidus, a part of the brain affected in Parkinson’s disease. To decrease the severity of Parkinson’s symptoms, patients may undergo a pallidotomy—where a lesion is actually burned into a patient’s brain. More recently, researchers have tried to implant stimulating electrodes in this part of the brain to alleviate Parkinson’s symptoms.

“It’s a bit of a paradox,” explains Anderson. “If you make a lesion in that part of the brain, it improves the patient’s symptoms, and if you stimulate through electrodes in that part of the brain, it also improves the symptoms. We are trying to understand why.”

Anderson and her colleagues think the interruption of the abnormal pattern, rather than the over- or under-stimulation of the nerve cells, may be helping relieve the symptoms.

“Abnormal patterns of nerve cell discharge may lead to the symptoms, so what we’d like figure out is how to overcome the abnormal patterns,” says Anderson. “My lab is trying to determine the mechanisms by which continuous deep-brain stimulation might act.”

Anderson presents the Distinguished Scientist Science in Medicine Lecture, “Listening to the Brain: What Can It Tell Us About Movement Disorders?” at noon, Thursday, May 22, in Hogness Auditorium at the Health Sciences Center.

Anderson received her Ph.D. in physiology and biophysics from the 91̽��in 1969. She was a postdoctoral fellow at the Rockefeller University in New York City from 1969 to 1971. She joined the 91̽��faculty as an assistant professor in rehabilitation medicine and an affiliate at the Primate Research Center in 1971. She joined the faculty in physiology and biophysics in 1973.

Among numerous honors, she has been a fellow of the American Association for the Advancement of Science since 1994. Anderson has served on the Advisory Board of the National Center for Medical Rehabilitation Research since 1999. She also is the director of the Western Medical Rehabilitation Research Network, funded by the National Institutes of Health to enhance rehabilitation research in the 15-state western region.

Dr. Helen Blau’s early scientific work focused on a lowly worm, a silkworm moth to be exact. But like the caterpillar in Lewis Caroll’s “Alice in Wonderland,” the worm pointed in a more interesting direction. Blau’s Ph.D. work on the biology of silkworm secretion led her to examine cell plasticity in mammals — whether or not adult stem cells present in bone marrow can function in other parts of the body in response to injury caused by trauma or disease.

Blau, the Donald E. and Delia B. Baxter professor of pharmacology and director of the endowed Baxter Laboratory in Genetic Pharmacology at Stanford University School of Medicine, has demonstrated that adult stem cells within bone marrow are dynamic and may have therapeutic applications restoring or replacing brain and muscle cells damaged by Parkinson’s disease, stroke, other central nervous system diseases, and muscular dystrophies.

“We’ve found that bone marrow-derived stem cells in adults have the capacity to contribute to diverse tissues, particularly brain and muscle,” says Blau. These cells may be precursors to tissue-specific stem cells in adults, such as healthy stem cells in blood or satellite cells in muscle.

Blau and colleagues studied brain-cell samples from women who had received bone marrow transplants from male donors. The donor male transplant cells had Y chromosomes. The researchers marked the healthy male donor Y chromosomes with a green fluorescent protein to identify them as different from the women’s cells. Stains of autopsy cells from the women revealed green fluorescent Y chromosomes in blood cells but also, surprisingly, in Purkinje cells in the brain.

In humans, Purkinje cells in the brain control balance and movement and are only known to develop before birth. According to Blau, the presence of green fluorescent markers of male bone marrow cells in these brain cells indicates something new.

“We think these adult stem cells, the green cells, are a repair squad that respond to damage,” says Blau.

To track the path of the hypothesized stem-cell repair squad, Blau and her team irradiated bone marrow cells in mice and then transplanted healthy bone marrow cells. Again the researchers marked healthy stem cells with a green fluorescent protein. Once injected into the irradiated mice, the green cells took over and made more green cells — and rescued the mouse from death. In the irradiated mouse, Blau said, the green stem cells were working as muscle fiber cells in more than 20 muscle groups.

“We have proof of this in muscle. When we exercised the irradiated mouse—exercise being a form of damage—the green cells later appeared in the muscles. The green cells derived from marrow could self-renew. We reproduced them as colonies of muscle cells in culture.”

Blau and her team have also found a significant difference in the abilities of different muscle groups to take up the green cells.

“Some muscles did better than others, in response to the same conditions,” said Blau. “Very active muscle cells had more green cells.”

After comparing the muscle fibers Blau’s group can get a 5 percent muscle fiber re-uptake, where there was only .1 percent or less re-uptake before.

“The Holy Grail would be having the ability to deliver a drug that recruits the stem cells where we need them and have an optimized re-uptake,” says Blau.

Blau presents the Annual Science in Medicine Lecture, “Stem Cells Within Adult Bone Marrow: Role in Tissue Repair,” at noon, Thursday, April 24, in Hogness Auditorium, room A-420, Health Sciences Center.

Blau received a Ph.D. degree in biology from Harvard University. She completed a postdoctoral fellowship in medical genetics, biochemistry and biophysics at the University of California, San Francisco, and joined the Stanford faculty in 1978. Among numerous awards, Blau received the Women in Cell Biology Senior Career Recognition Award from the American Society of Cell Biology in 1992, and the 1999 Excellence in Science award from the Federation of American Societies for Experimental Biology. She has served as president of the Society for Developmental Biology. Blau is the recipient of a National Institutes of Health MERIT award and is an elected member of the American Academy of Arts and Sciences and the Institute of Medicine of the National Academy of Sciences.

The 91̽��General Clinical Research Center (GCRC) has received a five-year grant renewal for $36 million from the National Institutes of Health (NIH). 91̽��Vice President for Medical Affairs and School of Medicine Dean Paul Ramsey is the GCRC principal investigator. Dr. John Brunzell, professor of medicine, is program director, and Karen Monteiro is the administrative director.

The GCRC, inaugurated in 1960, has a patient-care area located on the seventh floor south wing of 91̽��Medical Center (UWMC) and a satellite research area at Children’s Hospital and Regional Medical Center (CHRMC). There are currently 90 studies at the UWMC facility and 75 studies at CHRMC. These studies cover a wide spectrum of research from drug metabolism to gene and cell therapy. Proposed treatment protocols must pass UWMC/CHRMC and federal review before patient studies can begin.

More than 210 GCRC investigators are mostly from the School of Medicine, as well as from the Schools of Dentistry, Nursing, Pharmacy and Public Health. The majority of investigators have NIH grants. Some are also working with support from such organizations as the Cystic Fibrosis Foundation, the American Diabetes Association, or with grants from private industry.

Recent additions to the GCRC include a program for research subject advocates to protect and educate patients, a DEXA body composition/bone-density analysis machine, and facilities to conduct leukapheresis to isolate specific white blood cells. The GCRC plans to expand its gene and cell therapy protocols as well as optimize its operating expenses by remaining open during daytime hours on Saturdays and Sundays.

More information, including lists of personnel and an application for investigators who are interested in using some facilities, is available online at

Medical and health sciences researchers frequently conduct studies in vivo, within the body, or in vitro, in a test tube. Dr. Marcella McClure conducts her research in silico.

“My work is conducted in the computer environment,” explains McClure, associate professor of microbiology and computational biology at Montana State University. “I look at retroid agents in silico. I take empirically derived biological data sources, such as gene sequences, along with bioinformatics tools, like the Blast algorithm, and use human decision-making to generate new knowledge about the evolution, structure, and function of RNA-based life forms.”

Retroid agents are genetic agents that replicate or transpose themselves via a ribonucleic acid (RNA) intermediate and encode the reverse transcriptase. One example is the human immunodeficiency virus (HIV). Retroid agents have coevolved with multicellular life forms and cause diseases such as muscular dystrophy and hemophilia. Not all retroid agents are pathogenic. Experimental work indicates that retroid agents play a role in normal animal development and reproduction, including in humans.

However, when it comes down to the numbers, what is most important is that RNA mutates faster than DNA. McClure and her lab colleagues develop and test software to analyze RNA sequence data.

“RNA can mutate at least one million times faster than DNA life forms,” says McClure. “RNA evolves so fast that you can see molecular mechanisms that would take generations to see in a DNA system.”

Research using viruses provides model systems to apply to DNA mechanisms. For instance, gene splicing was originally discovered as a mechanism for viral messenger RNA before it was observed in host messenger RNA.

“One of my goals is to develop a browsible database of existing and new data relevant to retroid agents,” says McClure.

Already McClure and her colleagues have successfully predicted the function of several proteins based on sequence analysis. Her in silico predictions have been validated by crystallographic analysis in experimental laboratories.

McClure doesn’t think that the future of biology is all in silico.

“No algorithm is as good as the human eye at recognizing patterns at this level — the amino acids that are common among distantly related enzymes, for example, are those that fold into the active site of an enzyme or confer some important structural integrity,” says McClure. “People who do this kind of work are good at seeing patterns. What is a pattern to me, may not be a pattern to you.”

McClure will present “Hunting for the Reverse Transcriptase Gene: The Bioinformatics of Retroid Agents; Disease, Function and Evolution” at the WWAMI Science in Medicine lecture, at noon, Thursday, March 6, in D-209 Turner Auditorium, Health Sciences Center. The lecture is open to everyone.

McClure received a Ph.D. in molecular biology in 1984 at the Washington University School of Medicine in St. Louis. She completed a postdoctoral fellowship at the Center for Molecular Genetics at the University of California San Diego and was an assistant research professor in biology at UC San Diego and in ecology and evolutionary biology at UC Irvine. From 1993 to 1999 McClure was assistant professor of biology sciences at the University of Nevada Las Vegas. She joined the Montana State University faculty in 1999.

Among numerous honors, McClure received a National Institute of Allergy and Infectious Disease Research Career Development Award in 1996.

Dr. David Koelle and his colleagues at the 91̽��are looking for needles in a viral haystack.

“Herpes is a very big virus, with a genome of more than 160,000 base pairs,” says Koelle, associate professor of medicine in the Division of Allergy and Infectious Diseases. “That’s more than 10 times more complicated than the cold virus or HIV, in terms of numbers of amino acids encoded by the genome.”

Some people have severe recurrent herpes simplex virus (HSV), while others have very infrequent symptoms or are asymptomatic. HSV-1 is associated with cold sores; HSV-2 is associated with genital herpes. Researchers hypothesize that there is something different in the immune response to HSV-2 between persons with frequent symptoms and persons with asymptomatic infection. When a person infected with HSV-2 experiences an “outbreak,” viral shedding may or may not be accompanied by a skin lesion.

Little is known about how the body’s immune system recognizes the HSV virus. During a herpes outbreak, the immune system mounts a T-lymphocyte immune response when it detects a small number of proteins encoded by the HSV genome.

“To better understand this immune response, we need to know the identity of these short stretches of proteins produced by the virus and recognized by the immune system during a herpes outbreak,” says Koelle. “These protein chains are only eight to10 amino acids long.”

Koelle and colleagues study a glycosylated skin-homing molecule called cutaneous lymphocyte-associated antigen (abbreviated CLA). This glycosylated molecule coats the outside of a select minority of circulating T-lymphocytes. CLA is able to bind to another molecule, called E-selectin, that is specifically expressed in the skin. Therefore, CLA marks T-lymphocytes equipped to “traffic” to skin. And HSV is a skin-infecting virus.

Using CLA as a specific marker, Koelle and his team purify skin-homing lymphocytes from blood samples. These purified cells are rich sources of HSV-specific lymphocytes. Using genetic libraries of HSV type 2 DNA, the eight to 10 amino acid pieces of HSV that are recognized by HSV-specific lymphocytes are then determined.

“We are building knowledge of the immune system’s response to the herpes virus,” says Koelle. “One day a vaccine may be developed using our research on skin-homing molecules.”

Koelle presents “Home Sweet Home: Glycosylated Skin-Homing Molecules and Other Strategies Used by the T-Cell Response to Genital Herpes” at the Science in Medicine lecture, at noon, Thursday, Feb. 20, in A-420 Hogness Auditorium, Health Sciences Center. Everyone is welcome.

Koelle received an M.D. degree in 1985 from the UW. He completed an internship and residency in internal medicine at Tufts-New England Medical Center in Boston. From 1989 to 1992 he was a postdoctoral fellow at the 91̽��in infectious diseases. He joined the faculty as acting instructor of medicine in the Division of Allergy and Infectious Diseases in 1992.

Koelle is an attending physician at Harborview Medical Center, 91̽��Medical Center and the Seattle Cancer Care Alliance. He is also an affiliate investigator at Virginia Mason Research Center in Seattle and the Fred Hutchinson Cancer Research Center. Koelle’s research is supported by the National Institutes of Health and is made possible by the collaborative efforts of a large team of investigators in Seattle.

For many years molecular biologists have watched the process of cell division under the microscope.

“If a chromosome is gained or lost it’s often ‘curtains’ for the cell,” explains Dr. Linda Wordeman, associate professor of physiology and biophysics. “In a cancerous tumor, most of the cells appear to have the wrong number of chromosomes. Sometimes cells have mutations that allow them to escape a variety of checkpoints that the cell has in place to sense when a mistake in chromosome segregation has been made. And when this happens it is usually bad news for the organism.”

Wordeman will be talking about her research in the Science in Medicine lecture, Order from Chaos: Microtubule Dynamics and Chromosome Segregation, at noon Thursday, Feb. 6 in A-420 Hogness Auditorium, Health Sciences Center. The lecture is free and open to the public.

During cell division the individual chromosomes go through a random process of capture, movement and alignment on the mitotic spindle that, amazingly, ensures that the two daughter cells receive the exact same genes. Wordeman and her colleagues are studying microtubules, strands of protein inside the cell that help regulate which chromosomes go where during cell division.

“Microtubules serve as rails on which protein complexes and organelles are transported inside the cell and they also correspond to the skeleton of the cell — the cytoskeleton,” says Wordeman. “The weird thing about microtubules is that despite the fact that they contribute to the overall cell structure and shape, microtubules are actually very dynamic. It’s really amazing, if one looks at this in a time lapse film, the microtubules look like laser beams probing the cytoplasm.”

During cell division, the nuclear envelope breaks down. The microtubules attach to a specialized region on the surface of the chromosome: the centromere or kinetochore. The microtubules are actually polymerizing and depolymerizing all the time, allowing chromosomes to be “caught” on the microtubule. Once caught the chromosome begins to oscillate back and forth on the ends of the microtubule. This explains the root of the word kinetochore, which is Greek for “moving place.”

“When cells divide, the microtubules reorganize into this beautiful

spindle,” says Wordeman. “The spindle is composed of two poles that will eventually give rise to two daughter cells. The capture of chromosomes by the microtubule is a random process. And yet, once captured by the spindle the chromosomes all manage to make their way to the center and segregate to the poles — they have to do this with perfect fidelity.”

Wordeman and her lab group are also studying a protein that modulates microtubule polymerization and depolymerization. Mitotic centromere-associated kinesin (MCAK) helps ensure that the correct number and complement of chromosomes get to each daughter cell during cell division.

“You can have a serious mutation in a gene that is involved in cell

division, and as long as the chromosomes get properly segregated, you may not ever have cancer show up,” says Wordeman. “If, during the course of cell division, one cell drops or gains a chromosome by accident, then you are really on the way to tumor progression. So cell division has to be accomplished with perfect fidelity — we’re finding out that MCAK is one protein that regulates this process in conjunction with microtubules.”

Wordeman received a Ph.D. in zoology from the University of California, Berkeley. She came to the 91̽��in 1994 as an assistant professor of physiology and biophysics. Previously she was a postdoctoral fellow at the University of California San Francisco Department of Pharmacology and a visiting scientist at the University of Hawaii. Among her numerous awards are the National Science Foundation Predoctoral Fellowship, the Helen Hay Whitney Postdoctoral Fellowship and the Bank of America Giannini Postdoctoral Fellowship. Wordeman is currently on the editorial advisory board for Cell Biology International.

Each year 1.5 million Americans sustain a traumatic brain injury, according to the Centers for Disease Control and Prevention. This is eight times the number of people diagnosed with breast cancer and 34 times the number of new cases of HIV/AIDS. Of those with traumatic brain injury, 50,000 die and over 80,000 will have a life-long disability because of the injury.

“When someone gets a brain injury, some of the damage is immediate, but other things go wrong over the next days and weeks,” says Dr. Nancy Temkin, professor of neurological surgery and biostatistics. “Nobody understands the broad range of mechanisms that occur as a result of a brain injury. Seizures are one common result of brain injury. Loss of cognitive and functional abilities, such as the ability to hold a job, also occurs frequently. We do longitudinal studies on the occurrence of seizures and how people recover from brain injuries at periods of time between one month and several years.”

Temkin, a statistician, and her colleagues, especially Dr. Sureyya Dikmen, a neuropsychologist, and former colleague Dr. H. Richard Winn, a neurosurgeon, have completed two clinical trials of treatments to lessen the negative consequences of head injury. The completed trials were on medications to prevent the development of seizures and the current trial is enrolling patients for a study of a drug that may help improve functioning, as well as prevent seizures.

“During the first week after someone has received a head injury, they are given phenytoin to prevent seizures,” explains Temkin. “This has been the procedure for quite some time, based in part on the results of the first 91̽��study. Phenytoin is actually very successful at minimizing seizures in the first week. However neither it nor valproate prevent seizures after the first week and phenytoin may have adverse neurobehavioral effects when given over a long period of time.”

The third study Temkin and her colleagues are working on is treating patients with magnesium sulfate, commonly known as Epsom salt. Magnesium sulfate is thought to be a general neuroprotectant, according to Temkin. Magnesium may regulate calcium going into the brain cells and protect the cells from further damage in the week after the injury.

“The pilot data showed that magnesium sulfate had a positive effect on IQ—an area where brain injury can have far-reaching effects,” says Temkin. “If magnesium sulfate significantly decreases the cognitive and functional effects of a brain injury, it could substantially improve the quality of life for those who suffer a head injury. Doctors currently do not have any drugs that have been shown to improve long-term functioning after traumatic brain injury.”

Temkin received a Ph.D. in statistics from the State University of New York at Buffalo in 1970. She was a visiting scientist at the Imperial Cancer Research Fund in London and an instructor of biometrics at the University of Colorado Medical Center in Denver. In 1977 Temkin joined the 91̽��as an acting assistant professor of neurological surgery and biostatistics. She became professor in 2002.

Among her numerous awards, she received the Ciba-Geigy Award for the best controlled trial of the year. She is currently a member of the Centers for Disease Control and Prevention working group on mild traumatic brain injury.

Man doth not live by bread alone, but also by sodium, calcium, potassium, and magnesium. If the Bible had a chapter on basic cell biology, the preceding quote might have been included.

Human cells must control the movements of electrically charged particles called cations in order to perform their most basic functions. Under normal conditions, the most abundant cations outside of cells are sodium, calcium, and magnesium, while the most abundant cations inside cells are potassium and magnesium.

Dr. Andrew Scharenberg, assistant professor of pediatrics and adjunct assistant professor of immunology, and his lab group are interested in understanding how one of those cations, magnesium, gets into and out of cells.

“Magnesium has a unique role inside cells in that it attaches to adenosine triphosphate, also known as ATP, the energy molecules that do work in every living cell,” says Scharenberg. “Most enzymes which use ATP for energy need the magnesium-bound form, so making sure the right amount of magnesium is present is a very basic and critical cellular function. However, it is poorly understood how magnesium is taken up into cells and how the amount taken up is regulated.” He adds, “People have studied the uptake of magnesium using radioisotopes and by making measurements of the total amount of magnesium, but nobody has been able to molecularly identify the proteins involved in the process.”

Scharenberg’s lab has identified the first protein, TRPM7, that has a clear role in mediating magnesium uptake into cells. Special properties of TRPM7 are that it forms both an ion channel (a pore in the cell wall for magnesium to move through) and a protein kinase (an enzyme which modifies other cellular proteins). What this means outside of the lab is that drugs may one day be developed to alter the function of TRPM7 to selectively allow rapid magnesium uptake in cells.

“This is potentially medically important because altering magnesium homeostasis is something that physicians actually use therapeutically in some situations,” says Scharenberg. “For example magnesium sulfate therapy has long been used to treat preeclampsia.”

Women in late pregnancy can develop a serious condition called preeclampsia, which results in high blood pressure, edema, muscle contractions and even death if the condition of the woman is not treated.

“Magnesium sulfate provides the patient with increased levels of magnesium in the blood, which presumably acts at least in part by being taken up into the body’s smooth muscle cells and causing them to relax. A potentially more effective therapy would be to directly enhance magnesium uptake into cells in the smooth muscle tissue, as a drug able to activate TRPM7 might allow,” says Scharenberg.

Another possible use for identifying proteins involved in magnesium uptake is for treating asthma. During an asthma attack there is a severe constriction of the smooth muscle tissue in the lungs.

“Magnesium sulfate has also been studied for the treatment of severe asthma, with variable results,” explains Scharenberg. “This is all speculative, but selectively applying drugs in an inhaled fashion that would allow magnesium uptake in the smooth muscle of the bronchus should produce relaxation of the bronchi and bring relief to the patient.”

Scharenberg became interested in magnesium uptake while working as an immunologist and seeing children with single-gene immune deficiencies. The line of investigation which led to the identification of TRPM7 began with a comparison of genomic data of Caenorhabditis elegans, a soil nematode, with that of human lymphocytes to identify new proteins with some similarity to known ion channels.

“In the process of characterizing TRPM7, we knocked it out of a cell line,”

Scharenberg says. “The cells in that line died, and we were stuck for a long time. The breakthrough that happened almost serendipitously was finding that if you provide a supplemental amount of magnesium to cells deficient in this particular protein, they would grow. Now we’re able to use these cells to understand the mechanisms the body uses to control magnesium uptake into cells.”

Scharenberg presents the New Investigator Science in Medicine lecture

“Magnesium Homeostasis and Dual Function Ion Channel/Protein Kinases,” at noon, Thursday, Dec. 5 in D-209 Turner Auditorium, Health Sciences Building.

Scharenberg received a M.D. in 1990 and completed a pediatrics residency at the University of North Carolina School of Medicine in 1993. He served as a postdoctoral fellow in Dr. Jean-Pierre Kinet’s laboratory at the National Institutes of Health and at the Division of Experimental Pathology at Beth Israel Hospital until 1998. Scharenberg was on the faculty at Harvard Medical School for two years and joined the 91̽��Department of Pediatrics in 2000. Among his numerous awards, Scharenberg received a Pediatric Scientist Development Award in 1993 and the 2002 American Pediatric Society National Young Investigator Award.

A baseball pitcher warming up in the bullpen, an actress’ understudy and an airplane copilot, are all back-ups capable of performing an essential function when needed. In human physiology, many of the body’s vital functions have at least one back-up system.

Dr. Michael Schwartz, professor of medicine and head of the Section of Clinical Nutrition in the Division of Metabolism, Endocrinology and Nutrition, and his colleagues are working to identify brain pathways that respond to two different hormones — leptin and insulin — that inform the brain biochemically about how much fat is in the body.

“Both leptin and insulin are produced in proportion to body fat mass,” says Schwartz. “Leptin is produced by fat cells and insulin by the pancreas. Although insulin is better known for its role in the control of blood sugar, both hormones signal the brain regarding the sufficiency of body fat content. When people lose weight, falling levels of these hormones stimulate appetite and promote the recovery of lost weight.”

Because of these adaptive responses, it is difficult for people to stick to a diet and keep weight off. The feelings of hunger dieters experience are likely due, at least in part, to reduced insulin and leptin signals. Conversely, when normal people overeat, an increase of leptin and insulin signaling in the brain helps them to eat less and lose the excess weight.

“Leptin sends a signal into brain cells that modifies their function,” says Schwartz. “Over the past couple of years, we have begun to focus on the nature of that cellular signal and its relationship to how these brain cells respond to insulin. Although receptors for leptin and insulin are quite different, we think that both hormones activate the same biochemical pathway in specific subsets of neurons that control food intake.”

In obese people, more leptin and insulin are produced and yet food consumption is typically normal or increased, suggesting that they may be leptin-resistant. The leptin-sensing regions of the brain are not responding appropriately to the leptin signal and this allows for an elevated level of body fat to be maintained and defended.

“We need to clearly understand exactly what these hormones are doing in the brain if we are to understand how this signaling system becomes deranged and leads to weight gain. This might ultimately lead to the development of drugs to maintain normal body weight.”

Schwartz presents the Nov. 21 Science in Medicine lecture, “Insulin, Leptin and the Hypothalamus: Key Components of the System Controlling Food Intake and Body Weight,” from noon to 1 p.m. in room D-209,Turner Auditorium, Health Sciences Center.

Schwartz earned a M.D. in 1983 from Rush Medical College in Chicago, where he received the Nathan M. Freer Award as the Outstanding Student of the Graduating Class. He first came to the 91̽��in 1983 as a resident in medicine, completing a fellowship in endocrinology from 1987 to 1990. Schwartz was an acting instructor at the 91̽��and then joined the faculty as assistant professor in 1993.

Among his numerous awards he received the Young Investigator Award of the American Federation for Medical Research in 1994, the Young Faculty Award of the Western Society for Clinical Investigation in 1995 and was elected to the American Society for Clinical Investigation in 1999.

Connecting a monitor to the keyboard input on a computer’s CPU will result in neither the monitor nor keyboard functioning properly. The human brain has analogous, albeit much more complex, connections.

Some neurological diseases occur when the nerve cells in the cerebral cortex of the brain don’t connect properly during embryonic development. The cerebral cortex, consisting of many fine layers of organized nerve cells, is the outer shell of the brain controlling all voluntary muscle movement and sensory processing. Cerebral palsy, some forms of epilepsy and mental retardation may result when the layers of nerve cells are not organized properly, due to genetic mutation or other unknown factors.

“One of the things that goes wrong in these neurological diseases is the nerve cells are not sending their axons to the right place,” says Dr. Robert Hevner, assistant professor of pathology.

The axon of a nerve cell directs electrical messages to other nerve cells. In the cerebral cortex, nerve cells with similar functions are grouped together and often are formed at the same time during embryonic development — the cells have the same “birthdate,” and send their axons to the same target regions in the brain. But if the nerve cells grow their axons into the wrong targets, the brain wiring diagram is scrambled; just as the a computer keyboard does not function when plugged into the wrong input on a computer CPU.

Hevner’s lab studies the development of the cerebral cortex. Layer by layer the cerebral cortex forms with cells developing in one part of the brain and migrating to other parts. Using proteins marked with fluorescence, Hevner and his colleagues observe this cellular migration during development in embryonic mice.

“Ultimately we would like to understand and control the development of the nerve cells so that they can acquire the properties we want,” says Hevner.

One desirable property would allow using adult stem cell therapy to repair problematic nerve cell migration and connections. The Christopher Reeves Paralysis Foundation is supporting the Hevner lab’s work on identifying molecules involved in making connections between the nerve cells in the cerebral cortex and the spinal cord.

Hevner presents the first Science in Medicine Lecture in the 2002-2003 series at noon, Thursday, Sept. 26. The New Investigator Lecture, “Building the Cerebral Cortex: Neuron by Neuron, Layer by Layer,” will be in D-209, Turner Auditorium, Health Sciences Center. Everyone is welcome.

Hevner received received M.D. and Ph.D. degrees from the Medical Scientist Training Program at the Medical College of Wisconsin in Milwaukee. He completed a residency in pathology at Brigham and Women’s Hospital in Boston from 1992 to 1994. At Stanford University Medical Center from 1994 to 1997, Hevner completed a neuropathology fellowship and was an acting assistant professor of pathology for one year. He was an assistant adjunct professor of psychiatry (research) at the University of California San Francisco from 1998 to 2000, before joining the 91̽��faculty.

Among his numerous honors, this year Hevner received the UW’s Marian E. Smith Junior Faculty Research Award and became the 40th Edward Mallinckrodt Scholar.