A Conversation with Dr. Marion Sewer 
by Andrew Kerr
September 2007
Dr. Marion Sewer is a professor at Georgia Tech's School of Chemistry and Biochemistry.
Q - So here's what I understand about your research. You look at steroids (that's what athletes take to gain a competitive edge). You look at genes (which are an article of clothing). And you look at hormones (something teenagers have too much of). OK, so maybe I didn't understand it so well. How would you describe your research?
A - What we study are the pathways that control hormone production. The hormones that we study belong to a family called steroid hormones. The reason they're called steroid hormones is because they're all made from cholestorol. These are hormones like testosterone, estrogen, cortisol--cortisol being the stress hormone--and aldosterone. Aldosterone is important for maintaining blood pressure and keeping blood pressure levels regulated. We study the pathways that are involved in turning on cortisol production, primarily cortisol production in the adrenal gland.
Cortisol is important for making sure you cope with any kind of stressful situation, whether it be some kind of chronic stress--like say you bump your leg and have some sort of inflammation or something like that, or psychological.
Cortisol is also important for making carbohydrates. Every single morning, humans have high levels of cortisol secreted from the adrenal gland. What we look at are the signalling processes that lead to that release of cortisol every morning.
Q - What does cortisol do?
A - It's called a ligand. Ligands are small molecules--in this case a cholesterol derivative--that bind to proteins called receptors. The way that cortisol (and estrogen and testosterone) help the body cope with any physiological response is to bind to that particular receptor. Cortisol binds to a family of receptors called the glucocorticoid receptors. Estrogen will bind to the estrogen receptor.
The receptor is a protein, and the protein bound to the hormone now binds to DNA. Specific regions of the DNA correspond to genes that are important for whatever the physiological process is. So if it's cortisol, it would bind to DNA that would lead to increasing the production of enzymes that metabolize carbohydrates or increasing the production of molecules that help with the inflammatory response. If it's estrogen it would increase the production of molecules that lead to the development of secondary sex phenotypes in females. These molecules change the expression of genes, and so the production of specific genes.
So we look at what turns the genes that make cortisol on.
Q - The body does a pretty good job of taking care of itself. Is the idea to make improvements to the process?
A - Our studies with cortisol are primarily motivated just to look at the actual molecular mechanisms and, in a very detailed manner, how cortisol is made. We look at that primarily just for basic understanding.
We look at estrogen production by breast cancer cells, because high levels of estrogen and many other hormones are linked to cancer, so we are trying to figure out what leads to high levels of estrogen production. When estrogen is at high levels then you get more uncontrolled cell growth and tumor formation and ultimately cancer in tissues like the breast or the ovary.
Q - Why are some people so misfortunate as to be born with a tendency to produce more estrogen than is "safe"? Just an unlucky roll of the genetic dice?
A - It's very, very multifactorial. It's not just being born having mutations in genes. A lot of other factors contribute to cancer development: things that you are exposed to in the environment, toxic chemicals that are in the atmosphere, the chemicals in dietary foods that you eat, any exposure to radiation...Individually they don't necessarily have to predispose you to cancer, but in combination you have an increased risk.
Q - Has your research been applied to any kind of medical treatments?
A - Ultimately that's the goal, but direct application takes decades.
Q - What are some other potential applications of this research?
A - Cortisol production is also linked to an emerging condition called the metabolic syndrome. It's a syndrome where a combination of individual factors--obesity, type II diabetes, high cholesterol--lead to a pleiotropic effect. Cortisol has been linked to that. We're trying to see what dietary factors actually modulate and decrease cortisol levels. I have an undergraduate student looking at the factors that are present in grape skins. Many researchers have shown that there are lots of benefits--anti-aging, anti-cancer, all of these elixir-type benefits--to the chemicals that are found in grape skins and red wines. So we've been looking at one of those specific chemicals, a family of these chemicals in different soy products, products found in soy milk primarily, and looking at their ability to decrease the production of cortisol.
Q - How did you get interested in this field in the first place?
A - I spent four years at Vanderbilt in the department of biochemistry and started working on the genes that make cortisol. When I was in graduate school I looked into this same family of genes that are in the liver and their role in metabolizing drugs in the liver tissue, and making sure that the body excretes within a good amount of time any drugs that are taken medicinally.
Q - Do you foresee a future where people will be able to consume with wanton abandon all that they want, and then pop a pill that will allow them to metabolize all those substances?
A - Unfortunately, no. We would want that, but a lot of the drugs that are meant to get rid of all of these things that we take in, whether they be medicines or alcohol or anything, also produce reactions that lead to the production of even more toxic compounds in the body.
One of the problems is a lot of the switches that are turned on and off are multiple switches--you don't just get one switch. And where a good switch may be turned on, what may be a good thing in one part of the body may be completely bad in another part of the body!
Q - When you were in high school did you always want to go into this kind of research?
A - I was always interested in science. Because I'm from the Virgin Islands, I thought that I wanted to do marine biology. But there's only so much sea-water that you can smell and tolerate. Sea-water is great if you're swimming or just lying out in the sand, but having to do research with marine life was not as much fun as I thought it would be. So I turned my attention to health-related biology.
I knew I didn't want to be a medical doctor. It seemed like the real questions...you didn't really have the opportunity to really answer. About not just what this patient has, but why, and what's causing this?
Q - How long did you live in the U.S. Virgin Islands?
A - Until I got to college. My family is still there.
Q - Is the Virgin Islands a territory?
A - It's a territory. It's about 40 miles from Puerto Rico, about 18 hundred miles from Florida, midway between Florida and South America. There are three major U.S. Virgin Islands: St. Thomas, St. John, and St. Croix. St. Thomas and St. Croix are pretty large--each of them has probably about 50,000 people. The island I grew up on was St. John. There are maybe about 4000 people on that island. About 60 to 70% of the island are national parks. It's all of about 24 square miles.
Q - It's one of those places where I assume everybody knows everybody. Did you come to Atlanta because you wanted to get away from that?
A - Actually, I liked it a lot. But I realized that I don't like living in small towns in the states. And even Nashville, Tennessee--which many would say is not a small town--I found not quite city enough.
Going to Spelman was something I wanted to do from high school. My mom went to an all woman's college too, so it was kinda something I really wanted to do.
I went and visited it and I really loved it, so that sealed the deal.
When I was trying to figure out where to go to graduate school I looked at several universities, and I really liked the program at Emory, so I stayed in Atlanta for five more years, and then went to Nashville for four years, to Vanderbilt, and did research there.
When looking for a job it was never my intention to come back to Atlanta. But for my interests Georgia Tech was the best place to be.
Q - What do you like most about Atlanta?
A - To me the best thing about Atlanta is the airport! There's something to be said for being able to get on a plane and go anywhere in the world, and do it without having to hop from place to place. I like the cosmopolitan environment, lots of people from different places. Different places you can go and see different plays and listen to different types of music and go to different types of restaurants.
Q - Were you always a good student?
A - Yeah. I can't even pretend. I really, really liked school. I was one of those students who, getting sick and having to stay home from school was just like the end of the world.
Q - What should teachers know about getting kids fired up about science?
A - I remember having teachers that were especially good, like my chemistry teacher in seventh grade. He made science come alive. There was a lot of visual demonstrations. He was just very interactive, so learning became more three dimensional, not just reading and memorizing and spitting back facts on a test type thing.
When I was at Spelman I was a chemistry major. I think it was definitely because of those experiences in sixth and seventh grade.
Q - Where does the boundary lie between biology and chemistry anymore?
A - It's definitely very blurry, wherever it is, and that line is shifting all the time. Over time we've learned that in order to look at any one question there have to be multiple approaches. Science is becoming extremely integrated. To get a complete understanding of how things work you really have to have a little bit of physics, a little bit of chemistry, a little bit of biology, a little bit of computer science, and a little bit of math.
Q - I think back to the 19th century when doctors were doing one thing here and biologists were looking at specimens in cases over there. I guess we're reaching a point now where we know the basics and the next level is to synthesize.
A - And to develop the tools to get that knowledge. And a lot of those tools come from engineers. So, being able to be next to the people who are actually building the scopes or building the probes or the sensors to use to look at these tissues or specimens--that interaction is absolutely important.