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Lumen Scholar seeks new treatment to heart disease

Heart attacks and other cardiovascular conditions kill thousands of Americans every day, and as a high school student, that statistic turned personal for Elon University senior Amanda Clark. The biochemistry major focused her undergraduate research while at the university on identifying some ways that heart disease develops, which could in turn lead to better treatments, and her work is the latest to be featured in a series of E-net profiles on Lumen Scholars in the Class of 2011.

Elon University senior Amanda Clark (right) with her Lumen Prize mentor, associate professor Kathy Matera

Working with associate professor Kathy Matera in the Department of Chemistry, Clark examined a specific type of receptor found on cells that triggers an "alarm" to the immune system when the cell is invaded by a oxidized lipids. The native of Skaneateles, N.Y., is planning a career in medicine and hopes the knowledge she obtained through the Lumen Prize will serve her well in the years ahead.

Clark participated in the SURE undergraduate research program in 2008, working on Elon’s campus with Matera, and in 2009 she took part in the Summer Research Training Program at the University of California at San Francisco. An Elon College Fellow and an Elon Presidential Scholar recipient, she received the CRC Freshman Achievement in Chemistry Award three years ago and is a member of Beta Beta Beta, an honorary biology club. Clark is also involved with Phi Eta Sigma, and she is a member of Omicron Delta Kappa and Phi Kappa Phi.

She twice received an honorable mention in the Barry M. Goldwater Scholarship Program, a national competition that awards scholarships to students planning for careers in science, math or engineering.

The Lumen Prize, awarded for the first time in 2008, provides selected students with a $15,000 scholarship to support and celebrate their academic and creative achievements.

The program includes course work, study abroad, research both on campus and abroad, internships locally and abroad, program development, and creative productions and performances.

Clark recently sat down with the Office of University Relations to share details of her work.

It seems to me that your research begins with oxidized lipids that form in the body. What are oxidized lipids, and how do they develop?

“An oxidized lipid is just any fat that’s in your body that when attacked by other molecules becomes reactive. It’s very unstable and looking to attack other things. When these oxidized lipids are created, they end up being sucked up into your cells and killing the cell in the process. Those cells then go off into your arteries, sticking to your arterial walls and causing these plaque formations.”

Share a little bit about the biochemistry of what happens in the body when the immune system reacts to these lipids.

“When the immune system reacts to these lipids, there are certain receptors on the outside of cells. The one that I’m working with is called TLR-4, and when activated it sends out an alarm that something is going wrong in the body. This alarm acts throughout the body and calls different types of cells to the area, such as inflammatory molecules that are supposed to help the situation and clear away the plaques. Unfortunately, there are just too many cells called to the area. It’s almost as if this works too well. If there was a fire, you’d want firefighters to come to stop the fire, but if there are too many, there are too many people to get any work done. This is what happens within the body, and I’m trying to look at how this receptor is activated to try to prevent it from being activated.”

So the lipids trigger a "chain reaction" where too many molecules form into plaque buildups. And these plaque buildups are what we call atherosclerosis.

“Yes. Atherosclerosis is just a type of heart disease that is marked by the formation of plaques in your arteries.”

Which brings us to your Lumen Prize research. What are you doing to study the interaction of the immune system with these lipids?

“I’m specifically working with the receptor TLR-4 that I’ve been able to purchase, I’m looking at how it binds with another molecule known as fibrinogen, and this is just one of the molecules that’s regularly in your blood that is known to activate it. I’m looking at how they bind, where they bind and how well they bind. If you can answer all those questions, you can hope to create an inhibitor to block this interaction and prevent the immune cells from coming to the area.

This has practical applications down the road. The research you’re doing may help prevent heart disease.

“A lot of different drugs that are out there now stop interactions in the body and inhibit certain proteins. We know this has been done before, not specifically with this protein, but if we know how fibrinogen binds, we can maybe make a different version.”

So this is possibly another treatment in a series of medicines that we already know about?

Heart disease is a very complex problem. For a long, long time we just focused on changing the diet, to exercising well, to not eating as many fats. We found that even people who eat a perfectly healthy diet and do everything that’s recommended still have heart disease. There are other things that cause this. There are inherited traits that cause you to be more susceptible to heart disease. Now they’re realizing it’s more of an immune system problem than just a diet and exercise problem. That’s why we’re trying to look at the immune system, too, to find an alternative method to curing heart disease.”

Heart disease carries with it a personal connection for you. Can you talk about its impact on your family?

“My grandfather passed away in his early 40s before my parents were even married. Then when I was a junior in high school, my uncle also passed away at the age of 41, leaving behind two daughters, 2 and 4 at the time. He didn’t even know he had heart disease. It always makes me worry for my own father, who is older than my uncle was. He’s overweight and doesn’t exercise as much, but he’s still living. I’m just always worried that something’s going to happen to him, and I know that I’m very dedicated and persevere in all that I do, so I think I can really give back to the community by doing research on heart disease, and hopefully help my own family members one day.

Which brings us to your post-Elon plans. What do you hope to do after you leave here?

“I’ve been accepted to the University of Rochester School of Medicine, so I’ll be starting there in August and going for four years. I’m thinking about incorporating some research into that as well and taking a year off to do cardiovascular research before going on to be a cardiologist.”

How has the Lumen Prize shaped your goals? Would this research have been possible without it?

“This research absolutely would not have been possible without the Lumen Prize. I took $4,000 out of my budget to get this protein. Unfortunately, in the world of biochemistry, because the proteins I need come from the human body, it takes a lot to make them and to harvest them. I needed financial assistance to be able to work on this protein and do the research that I was interested in completing. I’m very grateful for all that I’ve been given through the Lumen.”

Eric Townsend,
Staff
5/8/2011 8:11 AM