Breath of Fresh Air

Summer 2017

Marsha Wills-Karp

Asthma expert Marsha Wills-Karp is bridging disciplines and campuses as chair of the newly formed Department of Environmental Health and Engineering.

Marsha Wills-Karp, one of the country’s best-known asthma scholars, has a long history of bringing together disparate groups of scientists.

The study that brought her to prominence—a 1998 paper demonstrating that a protein known as interleukin-13 plays a crucial role in asthma—grew from conversations between her own Johns Hopkins lab, which specialized in bronchial smooth muscle tissue, and her husband’s lab, which specialized in immune system proteins. The insights that came from those conversations opened a new paradigm in asthma studies. Then, in 2000, Wills-Karp and her husband, Christopher Karp, were hired by the University of Cincinnati to build from scratch a new pediatric immunology program. There, again, Wills-Karp found herself bringing together diverse disciplines—cardiologists, oncologists, geneticists, and immunologists—and coaxing them to break out of their silos to pursue new kinds of clinical research.

Now Wills-Karp, to be installed as the Anna M. Baetjer Professor in Environmental Health and Engineering in June, is embarking on her most ambitious discipline-bridging project yet. Last summer, she was named chair of the Johns Hopkins University’s new Department of Environmental Health and Engineering. The department is rooted in both the Whiting School of Engineering and the Bloomberg School of Public Health, and it encompasses the former Department of Geography and Environmental Engineering (at the Whiting School) and the Department of Environmental Health Sciences (at the Bloomberg School). It is the only program in the country that brings together a full range of environmental engineering and public health scholars within a single department.

“It’s a natural project for Hopkins,” Wills-Karp says. “The School of Public Health and the School of Engineering both have deep histories of working on water safety. It’s the Wolman tradition.” Abel Wolman, an American inventor and one of the most storied figures in Johns Hopkins history, pioneered modern methods of water purification and sanitary engineering. Wolman, who graduated in 1915, served on the faculty of the School of Engineering for 25 years but collaborated frequently with scientists at what was then known as the School of Hygiene and Public Health. Both environmental engineers and public health researchers have long-standing concerns with the safety of air, water, and soil, Wills-Karp says, and they can magnify their efforts if they work under a single departmental roof.

“This new department builds on strengths that are deeply rooted at Hopkins,” says Ed Schlesinger, the Benjamin T. Rome Dean of the Whiting School of Engineering. And Wills-Karp, he adds, is an ideal person to lead the project. “She’s very measured, very thoughtful,” he says. “She sees both the challenges and the opportunities involved in this sort of effort. I think she relishes the chance to have an impact both on environmental science and on Hopkins as an institution.”


A Path Changed by Poison Ivy

Wills-Karp embraced the life of the lab at a young age, but it took some time before she arrived at asthma as her life’s focus. As an undergraduate in the late 1970s at what was then known as Southwest Texas State University, Wills-Karp fell in love with science through a botany class. But there was a hitch: “I had the misfortune of being tragically allergic to poison ivy,” she says, “and this course involved gathering hundreds and hundreds of different plant specimens. I just kept getting exposed. Steroids weren’t helping. Finally, the college physician just said, ‘You’ve got to get out of this. You need to change careers if this is what you’re going to keep doing.’” (It may be fitting, then, that Wills-Karp wound up studying the perversities of the human immune system.)

After abandoning plant life, Wills-Karp completed a major in physiology. She stayed at Southwest Texas State for her master’s degree, studying in a lab that used innovative techniques to isolate individual cardiac muscle cells. Her thesis adviser, Joseph Koke, recalls her as one of the strongest students of his career.

“She had all the skills that people look for in a graduate student,” says Koke, who is a distinguished professor emeritus at Texas State University, as the institution is now known. “She was patient and persistent in the lab. You’d tell her what needed to be done, and she’d find a way to do it.” By the time she finished her master’s degree, Wills-Karp was a co-author of two published papers on how individual cardiac cells respond to oxygen deprivation.

For her doctoral studies, Wills-Karp entered the University of California, Santa Barbara’s Institute of Environmental Stress, an interdisciplinary center that sought to understand how human cells respond to pollution, aging, and other stressors. “We had a huge metal chamber that looked like something out of the military,” she says. “Inside the chamber, we had triathletes riding exercise bikes—these California athletes were in tip-top shape. We could alter the pressure and oxygen levels to simulate high-altitude environments. On some occasions, we would pump ozone into the chamber. This was where I first became interested in the effects of the environment on respiratory function.” After completing her degree, she obtained a postdoctoral research position at Yale University.

Wills-Karp found moving to New Haven a culture shock. “After living in Southern California,” she says, “it was like falling off the edge of the map.” But two fateful things happened during her short time there. First, at the urging of a colleague, she switched her studies from the smooth muscle of the heart to the smooth muscle of the lungs. “That was the point where I truly started to focus on asthma,” she says. Second, a mutual friend casually introduced her to Christopher Karp, who was beginning his medical residency at Brown University. They married less than five months later.

In 1987, Wills-Karp took a second postdoctoral position at Johns Hopkins while her husband began a fellowship at Georgetown. Her plan was to study in the lab of Harold Menkes, the head of the physiology program. Tragically, Menkes and his wife died in a car accident less than a month after she arrived. “It was a shock,” she says. “He was a great scholar. I was suddenly left to my own devices.”

Wills-Karp successfully applied for an early-career grant from the National Institutes of Health, and she continued to dig for the molecular mechanisms involved in airway hyper-responsiveness in asthma. At that time, scholars tended to believe that asthma attacks were triggered by a classic allergic response, with eosinophils and immunoglobulin E as the primary mediators. But Wills-Karp came to realize that the picture was not so simple.

Through conversations with her husband and his immunologist colleagues, Wills-Karp eventually decided to pursue a radical hypothesis. She had begun to suspect that asthma was driven in part by the function of T cells. Sure enough, after painstaking trials, she found that interleukin-13, a protein promoted by T cells, was fundamental to asthma. The discovery was published in Science in 1998.

“That finding about interleukin-13 has been reproduced hundreds and hundreds of times in both humans and mice,” says Stephane Lajoie, an assistant scientist at the Bloomberg School who has collaborated with Wills-Karp for nearly a decade. “It’s become one of the tenets of asthma research.” The discovery that this immune mediator (IL-13) is involved in asthma has led to the development of novel biological therapeutics for asthma. In fact, targeting of IL-13 in asthma has proved successful in asthma clinical trials; patients have demonstrated improved lung function.

Two years after that breakthrough paper, Wills-Karp and her husband were hired by the University of Cincinnati to build a new immunology program. They left Cincinnati in 2012, with Wills-Karp returning to Johns Hopkins as chair of the Environmental Health Sciences Department and her husband taking a senior position at the Bill and Melinda Gates Foundation.“For the last four years, we’ve had a long-distance relationship,” she says. “He’s based in Seattle, but he also travels all over the world looking at infectious disease. We’ve both accumulated a lot of air miles.”

In the last decade, Wills-Karp has continued to study the immune mechanisms involved in asthma, which have turned out to be even more complex than she suspected in the mid-1990s. She has advised pharmaceutical companies in their efforts to create drugs that blockade interleukin-13 and other asthma-related proteins. She has identified several genetic patterns that seem to increase susceptibility to asthma. And she has studied environmental triggers of asthma, including particulate matter in the air.

“Marsha is not afraid to go where the science takes her,” says Susan Ewart, a professor of large-animal clinical sciences at Michigan State University who has collaborated with Wills-Karpon studies of genetic risk factors for asthma. “She wouldn’t claim to be a geneticist, but when I came to Hopkins [as a graduate student in 1991] and said I wanted to take a genetics approach to asthma, she supported me and found me the resources I needed.”


Identifying Problems, Finding Solutions

Wills-Karp’s focus today is bringing together resources—both financial and intellectual—to help her new department flourish. She has a strong wellspring to start with: Two Johns Hopkins alumni, Yu Wu, MS ’89, PhD ’96, and Chaomei Chen, MS ’88, have donated $1 million to support collaborative research between the department’s engineering wing and its public health wing.

“The stipulation is that you have to have at least one partner from each of the two schools,” Wills-Karp says. “We hope to be able to support four or five projects each year. We had more than 120 people at our research retreat in January, and there was a huge amount of interest.”

One young scholar who is excited about the new structure is Johns Hopkins alumna Gaida Mahgoub, who earned a bachelor’s degree in public health studies in 2014 with a minor in engineering for sustainable development and then a master’s degree in 2015 in environmental health sciences at the Bloomberg School. “This kind of program is very much needed,” she says. “In both my undergraduate and master’s programs, I was always striving to combine engineering and environmental science to find ways to address public health needs with practical and hands-on solutions.” Mahgoub, who just started a fellowship at the Environmental Protection Agency, intends to apply to the new department’s doctoral degree program.

Bloomberg School collaborator Lajoie says that he expects Wills-Karp will help the department’s two wings function in harmony, and also give the program focus and momentum. “She’s very receptive, very open to working with different disciplines,” he says. “At the same time, she’s very precise, very meticulous with her data. She likes crisp, pithy texts. She wants all of her communication to have a purpose.”

For the last year, Wills-Karp has served on the advisory board of the Malone Center for Engineering in Healthcare, a collaboration between the Whiting School and the School of Medicine. In that role, she has had a front-row seat for one of the university’s most ambitious efforts to promote cross-disciplinary inquiry. She says she is confident that the new Department of Environmental Health and Engineering can have a similar impact.

“The simplest way to put it,” she says, “is that public health scientists can identify problems, and engineers are the solution arm. If water contamination is a problem, then engineers can find a way to mitigate that.” But she adds that her real hope is that the department can help young scholars collaborate in much deeper ways. Engineers and public health scientists, she hopes, can work together to assess environmental challenges and evaluate the effects of their interventions.

This past academic year, Wills-Karp has been focusing on how best to organize the undergraduate curriculum in the department’s engineering wing. “What we’re most excited about is building a curriculum that will allow engineers to work at the interface of engineering and public health,” she says. The department will soon announce the hiring of two faculty members with roots in both public health and engineering, she says.

“We also hope to put together a track that would allow engineering undergrads to apply to medical school,” Wills-Karp adds.

“Right now, we’re looking at the broad structure of the curriculum rather than at individual courses,” says Schlesinger. “We want to give students the opportunities and the resources to pursue their interests. We’re going to do everything we can to encourage cross-divisional research collaborations.”

Illustration of lungs

One potential area of collaboration involves Wills-Karp’s own specialty: asthma. In recent years, she has collaborated with Thomas Sussan, an assistant scientist at the Bloomberg School, on studies of household cooking and pulmonary illness in India. In certain rural areas of India, most families use biomass materials—generally wood or cow dung—to fuel their stoves. Sussan has collected air samples from such households and instilled them into the lungs of mice in his lab in Baltimore. He found that chronic, low-level exposure to such smoke can cause a variety of inflammatory and asthmatic responses, with the responses predictably varying according to the type of fuel and the intensity of exposure.

Could better-engineered stoves prevent those illnesses? “Biomass fuel stoves are an engineering challenge for sure,” Sussan says, “but it’s a very tricky issue. You need to design something that people will actually use, and something that they can use with minimal training. And you have to remember that these are some of the poorest people in the world, so these stoves can’t cost much.” The best way to approach the problem, he suggests, would be for small teams of engineers and public health scientists to work together. They should do their work on the ground, in close consultation with the people who use the stoves, bringing together engineering science, medical science, and social science at the point where they matter most.

It may take some time, Wills-Karp says, for faculty members from engineering and public health traditions to become comfortable working together. “But what I’ve seen is that the faculty members from both the Whiting School and the Bloomberg School are all highly committed to and engaged with environmental issues,” she says. “That’s what has brought us together.”