Research to prevent, treat vascular disease garners NIH award

Assistant professor of chemical engineering Eno Ebong takes the art of multi-tasking to a new level in her interdisciplinary search for the cause and treatment of vascular diseases that cause heart attacks and strokes.

Call it “multi-labbing”

In her two years at Northeastern, Ebong has undertaken experiments with researchers in fields as disparate as engineering, physics, pathology, molecular biology, and biological imaging. As the recipient of a new National Institutes of Health Mentored Career Development Award, she will draw on those collaborators, including bioengineering professor Jeffrey Ruberti, to uncover poorly understood cellular and molecular sources of atherosclerosis—the buildup of fatty deposits, or “plaques,” in artery walls.

Atherosclerosis is one of the underlying causes of heart attacks and strokes. According to the American Heart Association, 795,000 Americans experience strokes and 915,000 experience heart attacks each year.

“My goal is to understand the underlying mechanics and biology of what causes vascular disease,” says Ebong, “and then to develop engineering solutions, say, novel drug-delivery systems using nanotechnology, to try to reverse that disease.”

Eno Ebong’s NIH award exemplifies the momentum of Northeastern’s College of Engineering, notes dean Nadine Aubry. “The potential for breakthrough understanding of a long-standing fundamental scientific issue and transformative societal impact of Eno’s work is tremendous,” says Aubry. “I am delighted that NIH has recognized the importance of Eno’s work through this very competitive and prestigious award. Her research is a shining example of the role that engineering can play in further understanding complex biological systems and improving human health, in this case the millions of people around the world suffering from cardiovascular disease.”

The potential for breakthrough understanding of a long-standing fundamental scientific issue and transformative societal impact of Eno’s work is tremendous.
— Nadine Aubry, College of Engineering dean

The road to biomedical engineering

Ebong didn’t start out to be a biomedical engineer. Indeed, she didn’t even think she would study engineering in college when she started at the Massachusetts Institute of Technology in 1995, despite her love for math and physics in high school in Albany, New York. Economics was at the top of her list. “I didn’t have engineering role models, not even on TV, where there were plenty of doctors and lawyers,” she says. Then at a community event she met a man with a doctorate in engineering who worked at nearby General Electric Co. He opened her mind to the possibility. At MIT, mechanical engineering struck a chord.

But it wasn’t until she was in the doctoral program in biomedical engineering at Rensselaer Polytechnic Institute that she “really started learning about biology,” she says. Her interest in commingling disciplines had been piqued earlier: On a summer internship as an undergraduate developing ultrasound equipment at Hewlett Packard, she visited a medical clinic. “I went in with an engineering mind, saying, ‘Does the equipment work?” and saw the personal side—a nervous patient,” she says. “I realized that I didn’t just want to develop devices to detect disease; I wanted to find cures.”

Research that extends from the macro to the micro

The new NIH award will help Ebong pursue that goal at Northeastern.

On a macro scale, Ebong studies the trouble spots in blood-vessel geometry—the junctures, constrictions, and curvatures where blood is more likely to slam into a vessel wall and erode it, leaving lesions where fatty deposits can settle.

On a micro scale, she focuses on how the mechanical forces of blood flow affect the cells that line and guard those vessels, the endothelial cells. Going even deeper, she zeros in on the thin, protective gel-like layer of sugar molecules and proteins coating the surface of those endothelial cells—called the glycocalyx—to understand, on a molecular level, how lesions are allowed to form and what researchers can do to reverse the process.

09/14/15 - BOSTON, MA. - Eno Ebong works in her lab on Sept. 14, 2015.  Photo by Adam Glanzman/Northeastern University

Eno Ebong at work in her lab. Photo by Adam Glanzman/Northeastern University

The glycocalyx, says Ebong, is like a dense version of the hair on your arms, standing on end. It functions as a kind of sensor taking the measure of the environment. It triggers biological responses, helping blood vessels to adapt to the forces of healthy or disruptive blood flow.

“The same way you can feel the breeze on your arm, the glycocalyx can ‘feel’ the blood as it flows through the vessel,” she says. Scientists believe the glycocalyx may act like a “lever.” The force of healthy blood flow exerts a “pull” on the glycocalyx, which is anchored to the endothelial cell bodies. That pull remodels the cells.

“With remodeling, the cells become streamlined,” says Ebong. “Let’s say you’re in a really nice racecar, the ride is smooth. Essentially, the glycocalyx helps the cell remodel and become like a racecar. It evens everything out, the vessel walls remain clean, healthy.”

Studies of blood samples have shown that in disease conditions a lot of the glycocalyx is shed into the blood. With less of the glycocalyx attached to endothelial cell bodies, the “pull” and the endothelial cell remodeling changes.

“Let’s now say you’re in a bulky vehicle—you can feel the turbulence around you,” she explains. This mode of endothelial cell remodeling “leads the endothelial cells, which are normally connected, to detach from one another,” she adds. “They now become a sort of filter for cholesterol and inflammatory white blood cells to get in, leading to plaque growth in the vessel wall.”

Basic science leads to treatments

In her chemical engineering lab, Ebong constructs bioreactors—systems comprising fluids and human endothelial cells—to replicate both healthy and disruptive blood-flow conditions and to learn about the flow-glycocalyx-endothelial cell relationship. Her team combines these experiments with live animal studies to assess the validity of the results in real disease conditions.

In the long term, Ebong hopes to develop therapies that reverse that progression of disease. She’s already begun the process. In collaboration with professor Thomas Webster, the Art Zafiropoulo Chair in Engineering and chair of the Department of Chemical Engineering, and Srinivas Sridhar, Arts and Science Distinguished Professor of Physics, her team is working to understand whether they can leverage the nature of the glycocalyx, together with nanomedicine, to precisely deliver drugs.

“Numerous studies for drug delivery to fight diseases from atherosclerosis to cancer do not consider the vascular glycocalyx, yet seminal studies by our group show the possibilities of nanoparticles to penetrate the glycocalyx layer,” says Webster. “Based on our work, I am not sure I trust any results from studies that do not consider the glycocalyx. It is simply that important.”

Ebong embraces the research challenge. The passion that led her from MIT to RPI and then to a joint postdoctoral fellowship at the Albert Einstein College of Medicine and City College of New York before coming to Northeastern continues to inform not just her own work but her advice to students, whether they voice interest in a career in science or the arts.

“Follow whatever you’re passionate about,” she says. “If you’re hard working, you’re going to put in 100 percent, so enjoy what you do.” And take the time to find the “right fit.” “When you are passionate and good at what you do, you will be appreciated and your work will be recognized with awards like the one I just received.”