Dr. David Mangelsdorf, chairman of pharmacology at UT Southwestern Medical Center, has been awarded the 2012 Rolf Luft Award for research that has advanced understanding of nuclear receptor pathways.
The annual award from the Karolinska Institutet, the prestigious medical university in Sweden which is also home to the Nobel Assembly, honors one scientist worldwide for outstanding contributions in endocrinology and diabetes research.
A UT Southwestern faculty member since 1993 who was named department chairman in 2006, Dr. Mangelsdorf will receive the institute's award on March 16 when he delivers his prize lecture, "Nuclear Receptor Regulation of Nutrient Metabolism: From Worms to Humans." The award consists of a medal and cash prize.
In announcing the award, Karolinska Institutet officials commented that Dr. Mangelsdorf's "work on nuclear receptors led to landmark discoveries of how regulatory pathways govern cholesterol, lipid, and bile acid homeostasis. He defined crucial signal-transduction networks in their entirety by identifying the ligands, target genes, physiological functions and molecular mechanisms for several orphan nuclear receptors."
Nuclear receptors are proteins that turn genes on and off, serving as sensors that protect human cells against elevated levels of lipids. Dr. Mangelsdorf has identified several new molecules, or ligands, that activate so-called orphan nuclear receptors whose biological functions previously had remained unknown.
"At the time, I had no idea the orphan receptors that I was working on had anything to do with cholesterol or bile acids," said Dr. Mangelsdorf, a Howard Hughes Medical Institute investigator and professor of biochemistry at UT Southwestern. "That is where serendipity - a big factor in almost every discovery - played its hand."
Dr. Daniel K. Podolsky, president of UT Southwestern, said: "This award recognizes excellence in scientific discovery and the fruits of Dr. Mangelsdorf's determination to unlock mysteries surrounding human metabolism. This research holds important implications for the treatment of several diseases."
Early-career advice from Nobel laureate Dr. Alfred Gilman, regental professor emeritus of pharmacology, stuck with Dr. Mangelsdorf and set him on the path to discovery.
"Dr. Gilman told me, 'Mangelsdorf, whatever you do, do not practice safe science,'" Dr. Mangelsdorf recalled. "His meaning was clear: To answer a big question, you have to ask a big question, and take a big risk. That's exactly what I did."
Dr. Steven Kliewer, professor of molecular biology and pharmacology at UT Southwestern who runs a joint research lab with Dr. Mangelsdorf, said his colleague's work has helped biomedical investigators understand how nuclear receptors control metabolism.
"He's an extremely creative scientist who is fearless in terms of following the science, wherever it leads him," Dr. Kliewer said. "His work with the receptor DAF12 in parasitic nematodes has provided a new approach for treating and preventing parasitic infections. This has enormous human health implications."
Dr. Mangelsdorf gives equal credit to Dr. Kliewer, saying he "brought a fresh set of ideas and approaches when he was recruited here in 2002, and based on his initial discoveries, together we have had a string of exciting new stories."
Dr. Mangelsdorf was elected to the prestigious National Academy of Sciences in 2008. In 2007, he received the Edith and Peter O'Donnell Award in Medicine from The Academy of Medicine, Engineering and Science of Texas. Earlier awards include the Heinrich Wieland Prize from Boehringer Ingelheim, the Transatlantic Medal from the European Society of Endocrinology, the Gerald D. Aurbach Award from the Endocrine Society, the Adolf Windaus Prize from The Falk Foundation and the John J. Abel Award in pharmacology from the American Society for Pharmacology and Experimental Therapeutics.
A graduate of Northern Arizona University, Dr. Mangelsdorf earned a doctorate in biochemistry from the University of Arizona and completed postdoctoral work at the Salk Institute for Biological Studies.
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