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Close to the heart

Meron Mengistu gave the the graduate student address at Commencement 2008.

Over 30 million people around the world are living with HIV or AIDS, and 2.5 million new infections were diagnosed in 2007 alone. These staggering statistics have made the quest for new treatments increasingly urgent.

They have also spurred Meron Mengistu ’03, ’08 Ph.D. to pursue a future in virology.

Mengistu, who received her doctoral degree in molecular biology last week, first came to Lehigh as an undergraduate student.

During her tenure at Lehigh, she worked under the guidance of Linda Lowe-Krentz, professor of biological sciences, and collaborated with faculty in physics and mechanical engineering. Since her junior year, Mengistu has studied endothelial cells, the cells that line the blood vessels.

When she leaves Lehigh, Mengistu will incorporate her interdisciplinary work to help in the fight against HIV and AIDS. In her a postdoctoral position at the Institute of Human Virology, she will join a team that is trying to develop a vaccine against HIV.

The Institute of Human Virology combines the disciplines of basic research, epidemiology and clinical research in a concerted effort to speed the discovery of diagnostics and therapeutics for a wide variety of chronic and deadly viral and immune disorders - most notably the HIV virus that causes AIDS.

As a native of Ethiopia, Mengistu believes her heritage has played a large role in shaping her research interests in HIV/AIDS.

“This issue is close to my heart because I came here from Ethiopia, a country that has been and is being devastated by this disease,” said Mengistu. “Scientists have been working for almost 30 years to control the spread of this disease and to improve the quality of life for those infected, and I want to join the fight.”

Research that goes with the flow

At Lehigh, her research focuses primarily on atherosclerosis, a condition related to high blood pressure and associated with coronary artery disease. In atherosclerosis, the arteries harden due to deposits of plaque made from fatty substances, cholesterol, cellular waste products, calcium and others. The disease’s occurrence is intimately linked to the flow of blood through the arteries.

For example, Mengistu explains, plaque is often deposited regions of the artery where blood flow is disrupted and not streamline, usually in regions where the artery curves or splits into two.

These are regions with relatively low shear stress, a force that runs parallel to the direction of blood flow. But regions where the blood flows smoothly and in one direction have higher fluid shear stress conditions, which protects against plaque formation.

To study the effects of fluid shear stress on endothelial cells, Mengistu worked with Samir Ghadiali, professor of mechanical engineering. Ghadiali’s lab has developed a flow chamber that allows researchers to control fluid shear stress.

“This allows us to study endothelial cell response to different magnitudes of shear stress in order to mimic regions of the artery that are prone to atherosclerotic plaque formations and those that are protected from it,” says Mengistu.

Using this flow chamber, Mengistu studied the biochemical responses of endothelial cells to fluid shear stress.

“We study how endothelial cells distinguish between low and high fluid shear stress conditions and induce different biological responses that lead to different (observable characteristics),” she says.

Under low shear stress, the endothelial cells are cube-shaped, and the slender protein fibers that give the cell structure, called actin filaments, are randomly oriented throughout the cells. In conditions with higher shear stress, the cells elongate and actin filaments are aligned with the direction of flow.

Mengistu also studies signaling molecules, which initiate the cell’s response to changes in shear stress conditions.

“We are looking at the signaling events that are responsible in endothelial cell flow adaptation,” says Mengistu.

The final tier to Mengistu’s interdisciplinary research project was examining the mechanical properties of endothelial cells. For this, Mengistu worked in collaboration with physics professor H. Daniel Ou-Yang.

Mengistu used oscillating optical tweezers, a tool developed in Ou-Yang’s lab. These optical tweezers use strongly focused laser beams to trap particles on top or inside cells. These particles can then be oscillated at different frequencies to observe their mechanical properties.

“Optical tweezers allow us to overcome the challenges presented by the heterogeneous makeup of cells by giving us the capability to probe different regions of the cell,” says Mengistu. “This will give us a more holistic picture of endothelial cell mechanics.”

Mengistu’s willingness to learn and use tools developed for physics and mechanical engineering sets her apart, says her former mentor.

“She has had a fair amount of flexibility in what she’s doing. She is a great student,” says Lowe-Krentz, who adds that Mengistu is fun to watch as a scientist. “A lot of people are experts in one field and then collaborate with others. She actually does all the work of all three disciplines. And in the long run, that should do her well.”

--Rita Shankar

Posted on Wednesday, May 28, 2008

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