Interdisciplinary Approach to Treat Vascular Diseases

ChE Assistant Professor Eno Ebong is using interdisciplinary research to search for the cause and treat­ment of vas­cular dis­eases that cause heart attacks and strokes.

Source: News @ Northeastern

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.”

Related Faculty: Eno E. Ebong, Jeffrey W. Ruberti, Srinivas Sridhar

Related Departments:Chemical Engineering