With a transdisciplinary team of social, behavioral, and biological scientists, Sarah Gehlert is studying how living in a distressed community may be a cause of breast cancer.
By Carl Vogel
It's the afternoon before Valentine's Day, and Sarah Gehlert has a red heart and a folded pink ribbon pinned to her blouse. Sitting at a conference table at the University of Chicago's Institute for Mind and Biology, she's trying to steer the conversation to a productive resolution of a seemingly mundane task: how to share computer files among the members of the Center for Interdisciplinary Health Disparities Research.
Gathered for CIHDR's monthly leadership team meeting is an impressive and impressively eclectic team of University social workers, psychologists, physicians, pathologists, and molecular geneticists. They're working together to answer a medical mystery: Why, despite the fact that white women are more likely to develop breast cancer, are black women are more likely to die from it?
The center was founded four years ago by three of U of C's heavyweight researchers: Gehlert, SSA's Helen Ross Professor and an expert on the intersection of social work and health issues; her co-director Martha McClintock, the David Lee Shillinglaw Distinguished Service Professor of Psychology and the founding director of the Institute for Mind and Biology; and Olufunmilayo "Fumni" Olopade, a professor of medicine and a hematologist/ oncologist who has won a MacArthur "genius grant" for her work. CIHDR's unique research is looking at what may be a big answer to their core question: links between living in a disadvantaged neighborhood and the development of "triple-negative" breast cancer—which develops in women at a younger age and is more lethal than other cancers— in African-American women.
Right now, though, McClintock is wondering why she can only find full tracking information in the shared computer database for two of the women in the center's key study. She asks Maria Tretiakova, an assistant professor of medicine and a key member of the center's tissue core team, about accessing the data, but they can't agree on how to make it available. Everyone is starting to get a bit testy.
"We can't publish without this," Gehlert points out. It's a startling thought—that years of work could be brought low because of a lack of clarity about how many women were approached to participate, agreed, and were tested—and clearly one that hadn't occurred to the doctors and pathologists who comprise the tissue core, which runs diagnostic tests on the women's cancerous cells. After some discussion about liaisons and procedures, the group finds a consensus and a potential crisis is averted. "A big project can fall apart on a single thing," gravely concludes Thomas Krausz, the tissue core leader and director of anatomic pathology at the University's department of pathology.
"It was a perfect example of transdisciplinary differences," Gehlert explains a few weeks later. "Maria was wondering why she was even being asked about all this, because we could gather all that information in the medical system. What she didn't realize is that those of us who aren't part of the U of C hospitals don't have access to the data in the medical school, because of federal regulations about patient privacy."
Bridging gaps big and small is a big part of Gehlert's job as the principal investigator and director at CIHDR. Interdisciplinary research is predicated on the idea that by mixing the expertise and insights from a variety of academic research, we can find answers that aren't available through the traditional disciplinary silos. Researchers who go even further, in transdisciplinary research, don't just share results at the end of their studies, they work in concert throughout the process.
"It's a perfect fit for social work, which has always taken a holistic approach and tries to look at all the determinants of a phenomenon at once. Having so many different aspects and variables—that all makes sense to me because of my background in social work," Gehlert says. "And when you're the director, you have to know about working in groups and bridging different points of view, and that's a natural role for a social worker as well."
But Gehlert's contribution to CIHDR is not limited to her role of "keeping everyone focused on the big picture," as she puts it. She's leading her own multidimensional research project of the more than 300 African- American women who have been diagnosed with breast cancer and agreed to participate in the study, requiring dozens of focus group discussions, hundreds of interviews with the women, the creation of a new way to model neighborhood dangers, and ongoing outreach to the neighborhoods being studied (her heart and ribbon pin is a bit of cheer for a Valentine's Day party tomorrow for dozens of the participants).
Mix it all together, and Gehlert is at the vanguard of a project that utilizes all the skills required to conduct social work academic research, from attracting funding to meeting with neighborhood residents, from managing a diverse set of partners and projects to writing up the findings to be published. "We're moving university research off campus and into the community and working together in a really new way," she says. "I'm really excited by it all."
"[At CIHDR], she's dealing with a group of people from very different backgrounds, speaking different languages, and from different cultures, using different methodologies," says Tim Rebbeck, a professor of epidemiology at the University of Pennsylvania and the director of a similar program that is examining ethnic differences in prostate cancer outcomes. "Her approach to the project and the group at Chicago is amazing. They're doing something highly unusual and very, very successful."
Health disparities occur by race, ethnicity, gender, socioeconomic status, and sexual orientation. Black adults are twice as likely as whites to be diagnosed with diabetes, for example, and mortality rates for black men with prostate cancer have increased over the last 30 years while dropping for whites. The same story holds true for breast cancer. The rates for black women dying from the disease rose from 39.2 per 100,000 to 44.1 in the last three decades. For white women, they fell from 31.8 per 100,000 to 23.8.
Hereditary and behavioral differences account for some of these gaps, but not all. Social circumstances and environmental factors place minority groups at a disadvantage in terms of health and disease, and traditional research methodology is unable to discern why. "You can't look at just the medical or the social factors by themselves and figure this out," Gehlert explains. "To address complex human problems, you have to look at all levels of influence."
To develop more nuanced studies of issues such as these, the federal National Institutes of Health began an initiative in 2003—the Centers for Population Health and Health Disparities—and put out a call for transdisciplinary research projects. McClintock, Gehlert, and Olopade, joined by Suzanne Conzen, an associate professor of medicine who specializes in molecular biology, were awarded a $9.7 million NIH grant to launch CIHDR, one of eight such centers nationwide.
CIHDR's research model is built from four intertwined projects: McClintock is monitoring the effects of environmental factors on mammary tumors in laboratory rats. Conzen is studying the rate of tumor growth and response to chemotherapy in transgenetic mice. Olopade is looking at the types of tumors found in the sample of black women on the South Side and another in Nigeria. And Gehlert is connecting what is learned about tumorigenesis in the animal models to the lives of the women in the cohort Olopade is studying in Chicago.
"It all really starts with what we learn from the effects of the environmental conditions on the rats," Gehlert says. "We can watch what happens over the course their life cycle and see if we can see the same kind of phenomenon in the neighborhood." The big insight was when McClintock's group found that socially isolated and hypervigilant rats develop mammary cancers 40 percent younger, at four times the rate, and have larger and more aggressive tumors than a control group of rats that lived together. "When Fumni saw that data, she practically fell out of her chair because the age incidence of developing a tumor in our rats matched the age issue of African- American women," McClintock says.
Working in concert, the CIHDR researchers have created a hypothesis about breast cancer rates in African American women that, greatly simplified goes like this: Living in a dangerous neighborhood leaves women alone and without much human contact, circumstances that causes stress. Stress causes genetic mutations, which in turn lead to malignant breast cancer, particularly triple-negative cancers.
The theory is based on "downward causation," the concept that determinants at the social and environmental levels can change the way DN A and cells function. We know that from 70 percent to 80 percent of human breast cancers are due to acquired mutations of breast cancer genes, rather than hereditary factors. CIHDR's theory argues that living in isolation in a dangerous situation is a chronic stressor—Gehlert and her colleagues coined the term "acquired vigilance" to describe the status of constantly being on guard against threats. CIHDR's investigators have identified stress hormone receptors that are triggered by this psychological state and then activate biochemical pathways known to increase tumor cell survival.
"Coming out of the results of Sarah's work, we've been focusing on the constellation of depression, vigilance, isolation, and ennui, and refining how we can think about measuring those factors in the rats," McClintock says. "We've also been very influenced by Suzanne's work and the surgical pathology to look at the tumors, diagnose the estrogen and measure the hormone receptors."
Gehlert's research for CIHDR started with an advisory group from the community that helped her team develop a series of focus groups to better understand beliefs, attitudes, and knowledge about breast cancer among African Americans on Chicago's South Side. "We created a procedure to hold the sessions in the neighborhood, where a dozen or so people could meet and feel comfortable. Nobody would know anyone else in the room, and the questions were open-ended, so we didn't inadvertently get a response because we led the group to an idea," Gehlert says.
More than 500 men and women participated, creating a wealth of data buried within thousands of pages of transcripts. "We're now going through it all and finding themes, such as a general mistrust of the health care system and that other life concerns the women have are seen as more important than thinking about breast cancer," says Rebecca Wintzer, an SSA doctoral student who is combing through the transcripts using qualitative research methodologies, including manual coding and specialized software. "We're finding out that a lot of women are discouraged by breast cancer screenings and mammograms—they're not insured or they're being told that they're not the right age. It gives us ideas about why African-American women may not be receiving appropriate treatment."
With input from the focus groups in mind, Gehlert created one-on-one interview questions and procedures for the women in the study. Starting four to six weeks after Olopade's team has a woman's tumor tissue for analysis, the interviews—all in the women's homes—take more than 18 hours in all, with three two-day sessions spaced six months apart. Each is conducted by one of a dozen interviewers who went through training that included practice interviews and sitting in on a session at least twice before conducting one.
The questions cover everything from experiences at the hospital to how the women feel about where they live. During the first session, the interviewer leaves the woman with salivettes—an oral collection tube that allows researchers to measure the level of stress hormones in the woman's body. By taking a sample three times a day for four days straight, the team can monitor stress over time, and not just rely on the women's own report of how she's feeling.
The same interest in augmenting subjective self-reporting led Gehlert to develop a unique system to map each subject's immediate built environment. By linking data from the Chicago Police Department and other city agencies, such as violent crime incidents and health indicators, with information gathered from a walking tour, Gehlert's team is able to quantify a measure of isolation and stress.
"When a woman is living alone in a first floor apartment in a very distressed neighborhood, she has to be ready for something bad to happen 24/7. And if she's unable to leave her apartment much because of danger in the community or to meet the neighbors because of the type of neighborhood it is, that's going to be very isolating. Those are the kind of environmental factors we've learned have an impact in the animal models, and we need to measure them for our human project," Gehlert explains.
The mapping project looks at a four-block radius around each subject's home. A team of two go out at least twice to document a checklist of factors, including the type and condition of the housing stock, whether there are local parks, libraries, and grocery stores (including if fresh produce is available), the number of people on the street and their activities, the rate of automobile traffic, and the presence of graffiti and trash. "In the end, we're trying to come up with a risk index for that exact address," says Charles Mininger, a doctoral student at SSA who is leading the project. "We've looked at the literature and surveys, and we don't think anybody's done something at this level of specificity before."
Gehlert and her colleagues are hopeful that both the type of research they're doing and the findings about breast cancer will have an impact. The group has already published in a fittingly eclectic set of journals, including an NIH report and two articles in Health Affairs. Reporters from Chicago Public Radio to the Times of London have covered their work.
Blase Polite, a medical oncologist at the University of Chicago who is researching survival disparities for diseases like breast and colon cancer, says his work would not be the same without CIHDR. Under Gehlert's advisement, he waited to create a survey based around healthcare options until he had talked with a number of cancer patients in open-ended conversations, a move that opened his eyes to an entirely new facet of the impact of faith on people's medical decisions.
"I'm not a Ph.D. social scientist, and my work would have not looked the same without CIHDR. Sarah helped me use the tools and approach from the social sciences—starting with a model of what I thought was happening, then talking in depth with men and women about their thoughts in a structured way. It's really proved to be invaluable," Polite says.
The team at CIHDR have already started to reach out to African-American neighborhoods on the South Side of Chicago to raise awareness of breast cancer (see "CIHDR in the Community"), and if they can prove the causation of dangerous communities on early onset breast cancer, the hope is that public health concerns will join poverty reduction and public safety as reasons to improve distressed neighborhoods.
"We should start thinking about increasing features in a community that allow women to have safe social interactions. That includes lowering crime and requiring absentee landlords to keep up their buildings," Gehlert says. "But it might also mean a recurrence of settlement houses to serve the communities. I think we're just starting to scratch the surface on what this kind of research will do."