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
"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.
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
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."