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The Best of the Best

David Mangelsdorf's research is leading to important breakthroughs in treating vexing health conditions such as heart disease, cancer, cholestasis, atherosclerosis, infectious parasitic disease, and gallstone disease. Now the chair of the Department of Pharmacology at the University of Texas Southwestern Medical Center, Mangelsdorf is the first Northern Arizona University alumnus elected to the prestigious National Academy of Sciences. He's also the first to admit he never imagined his research would lead to new drugs that could potentially battle metabolic syndrome or obesity.

But Mangelsdorf learned a long time ago—in classrooms on Northern Arizona University’s campus, en route to undergraduate degrees in aquatic biology and chemistry—to  follow the science.

"You can be as smart as you want, you could do all the right experiments,but it's nothing if you don't have a little bit of serendipity," he says.

Discoveries in health

In the lab, Mangelsdorf focuses on discovering the components of pathways that turn genes on and off in a cell's nucleus, as well as the nuclear receptor proteins that turn genes on and off when they meet a trigger molecule called a ligand. His research has led to greater understanding of hormonal effects on human health. For example, Mangelsdorf discovered that a cholesterol derivative is the ligand for a nuclear receptor called LXR, which plays a key role in cholesterol regulation. Mangelsdorf then found that bile acids serve as ligands for another receptor, FXR, which works with LXR to reset lipid metabolism after a meal.

"There are a couple of clinical trials going on based on the pharmacology that we developed around discovering that receptor," he says. "So, it's now in the clinical trial phase for fighting cardiovascular disease."

Without an open mind—a trait that Mangelsdorf urges the up-and-coming generation of scientists to develop—it's likely that crucial findings may be left undiscovered.

The path to Northern Arizona University

As a high school student in Kingman, Arizona, Mangelsdorf was fascinated with Jacques Cousteau, and dreamed about becoming a marine biologist. He wrote to the admissions office of Scripps Institute of Oceanography, but his letter ended up at Scripps Women's College by mistake. It eventually landed in the right hands, and he received a letter from the Institute, explaining that it only offered graduate programs. The letter advised him to consider getting the "good, solid undergraduate experience" he needed closer to home: at Northern Arizona University.

"They directed me toward NAU's programs…I was blown away by that," Mangelsdorf says. "They said that NAU had one of the best vertebrate biology programs in the country…and one of the best forestry schools in the world."

When he landed in a class taught by John Wettaw , who is still a friend to Mangelsdorf—he was turned on to chemistry so much that he added it as a second major. Another course in biology, taught by parasitologist Stanley Wilkes, is "burned into my memory," he recalls.

"The scientific background I got from the courses I took at NAU clearly helped when I went out on the market for a graduate school," he says. "My faculty members in graduate school were so impressed with what I already knew…the education and foundation that was laid was important."

The grand prize

It wasn't just a foundation—it was also the springboard to excellence in science. Mangelsdorf's groundbreaking work in the development of new treatments for battling high cholesterol and other diseases was rewarded with an appointment to the National Academy of Sciences, which is one of the highest honors for an American scientist.

"That's the grand prize—that tells you that what you did was worth it and you're respected for it and people understand it," Mangelsdorf says. "It's the culmination of every scientist in America's dream."

It's a dream Mangelsdorf hopes that budding scientists at Northern Arizona University realize is possible, if they take advantage of the opportunities around them.

"You need the wisdom and ability to understand that things aren't always what they seem," he says. "Don't fit the experiment to your hypothesis; fit your hypothesis to your experiment."