Staci Bilbo's research featured on Duke Today

How Staci Bilbo's research could illuminate human brain development:

http://today.duke.edu/2012/05/bilbo

DURHAM, NC - Researchers sometimes go to great lengths to construct animal models that could shed light on human problems. Staci Bilbo, in studying the immune system and brain development, has been known to replicate life in a low-income housing project for her rodents and enroll the pups in a rodent after-school program. All this to determine what happens to human babies born to stressed mothers exposed to air pollution and what can be done about it.

"We're trying to figure out a behavioral intervention, like an enriched environment for the offspring," Bilbo said. "We take the pups to a playroom for a few hours each day and ask whether that reverses any of the negative effects we've seen."

Bilbo, assistant professor of psychology and neuroscience at Duke, is one of only a few researchers studying microglia, immune cells that reside in the brain. She looks at what happens in neural-immune interactions in the brain under various conditions and how that affects brain development. Her work has won widespread acclaim. Many of her research papers have been published in highly respected journals, and she recently received the Frank Beach Young Investigator Award from the Society for Behavioral Neuroendocrinology. She has been a very successful grant writer and was elected to her department's advisory committee while an assistant professor. Her fall class evaluations were among the top five percent from across the university. All this in the first eight years of her career after graduate school.

"One of the most exciting things we're doing is trying to model socio-economic status in animals," Bilbo said. Poor neighborhoods not only have poor housing conditions but more maternal stress, fewer resources and greater exposure to toxins because they're usually located closer to highways -- all cumulative factors people in poor neighborhoods face that people in wealthy neighborhoods don't. Researchers rarely model cumulative risk factors, she said, because "throwing a bunch of factors in together gets very messy. "But people are messy."

Through work done in collaboration with a research grant from the Environmental Protection Agency and funded by a Research Incubator Award from the Duke Institute for Brain Sciences (DIBS), Bilbo has found that giving air pollutant particles to rodent pups themselves doesn't change their brain or immune system much. But stressing the pregnant mothers while exposing them to pollution has a hugely synergistic effect on their offspring, she said.

"They're much worse off," she said of those pups. Once the baby mice grow up, they have cognitive deficits and anxiety and changes in metabolism that make them heavier. Bilbo's research is designed to tease apart any behavioral change in the mother that is mediating something in a pup from a physiological effect, such as transferring stress hormones while nursing the pup. Non-traditional in her methods, she is one of a few researchers in her field to meld neuroscience and immunology techniques, employing flow cytometry, a method of sorting cell types to find out what brain cells are producing.

"We're very interested in what about mom is producing the effect and how that's transferred to her pups," Bilbo said. "Is she changing her behavior? Or are her stress hormones getting to the fetus and interacting with the toxin exposure in an inflammatory cascade?"

In graduate school, Bilbo began with the notion of plasticity in the immune system: External events could impact the immune system, which would respond in an adaptive way to organize other systems in the body. Her research is built on emerging research that showed that stressors and nutritional deficiencies during development could permanently change metabolism, stress reactivity, anxiety and propensity for depression later in life. She figured it might affect the immune system, too.

First, Bilbo examined the interaction of the immune system and endocrine system. When she reduced the length of time Siberian hamsters were exposed to daylight, their bodies responded as if it were winter -- their fur grew thicker and whiter, their reproductive systems turned off and their immune systems kicked into high gear.

Randy Nelson, her doctoral mentor at Johns Hopkins University (he has since been successfully recruited to Ohio State), said Bilbo stands out in her ability to take information from many disparate fields and put it together in new, fresh ways that cause other researchers to say, "Of course!"

"But it took Staci to figure it out and do the critical studies," Nelson said. "She's brilliant in looking for unexpected outcomes and following those up in her work." Bilbo's interest in the brain's role developed as she studied sickness behavior. She discovered that the organized responses to illness an animal exhibits -- lethargy, fever, reduced interest in eating and drinking -- were adaptive, not pathological, behaviors.

"They're recuperative behaviors that help you overcome the infection more quickly," she said. "They're very cool because they're a motivational shift. You're not motivated to do the same things you usually do, and you have a very strong motivation to sleep. That implicated the brain."

Brain development is a very underexplored area, she said, yet it presented an interesting plasticity experiment: short-term plasticity resulted in long-term changes.

"The brain's development must be the time that all of these different things were set up," she said. "I looked at neuralimmune interactions in the brain and got immediately fascinated because I found all this early evidence that the immune system was critical for brain development."

Harris Cooper, chair of Duke's Department of Psychology and Neuroscience, said that Bilbo's research on immune system compromise influencing risk or resilience for later brain functioning and behavior speaks to a broad spectrum of issues that interest scholars across psychology and other social sciences.

"Her work helps us understand serious concerns about the implications of childhood poverty," Cooper said. Bilbo is one of the pioneers in the field of understanding how the inflammatory response of the immune system affects other areas of functioning later in life.

Quentin Pittman, a neuroscience researcher at the University of Calgary, is familiar with Bilbo's work and, like many others in the field, holds her research in high regard. Her studies of microglia, the white cells in the brain that act as scavengers against infection, and how they are modulated by early infection, has implications for vulnerability in adults.

"Many central nervous system diseases have a very strong inflammatory component to them -- Alzheimer's, Parkinson's, MS, dementia -- and the states of obesity and autism," Pittman said. "In the area of neuroinflammation, she's the most promising young investigator I know of."

Bilbo has recently uncovered a new class of molecules that could be useful in treating addiction. Yet she doesn't ignore the importance of behavioral interventions, like maternal bonding, exercise and the rodent playroom fun.

"You can't re-create a behavioral experience with a pill," she said. Bilbo grew up mainly in Texas and received an undergraduate degree in psychology from the University of Texas at Austin. She did her graduate work at Johns Hopkins University, obtaining her Ph.D. in psychological and brain sciences in 2003. She conducted postgraduate work at the University of Colorado's Center for Neuroscience, where she continued to be extraordinarily productive in writing and publishing research papers.

She joined Duke's faculty in 2007. She has been invited to speak at dozens of colloquia in the past few years and has published more than 40 articles and several chapters and abstracts, and serves as a reviewer for many well-respected journals. In an era of tight funding, she secured major grant funding for three path-breaking studies that she is now conducting simultaneously. She recently completed two others.

Bilbo is uncommonly efficient, said Nelson, her mentor at Johns Hopkins. When she had an idea for a project, he remembered, she would write up a protocol and explain what she planned to do in the study. She included the previous research on the topic, her hypothesis and what she intended to do with the results, and laid out the methodology. Once he approved her project, she was off and running. As soon as she got the results, she'd plug those in and take a few days to write the discussion section.

"Within a week of the study being completed, she had a paper to submit, and a very nice one at that," Nelson said. "She was the easiest grad student I had -- very independent, smart and highly motivated. She was the entire package."

Her longtime friend Jacqueline Wood attested to Bilbo's efficiency. Wood remembers sitting next to her in class, as an undergraduate, watching her take copious yet concise notes in a compact notebook.

"She's very observational," Wood said. "She's very patient and a good listener."

Wood also saw Bilbo's maternal side, not just with her whippet and cats at home, but the creatures in her lab. "She took very good care of her laboratory lizards, and the crickets she fed to them," Wood said.

Maternal bonding, among other behavioral interventions, can set the trajectory for the way the brain works for the rest of the lifespan. Bilbo's research underscores the importance of prenatal care and resources for moms, something the U.S. doesn't do a very good job of, according to Bilbo.

"The pregnant mother is a vastly underexplored slice of the population," Bilbo said, "and arguably one of the most important."