May 2, 2013

Nobel laureate describes decades-long pursuit of cholesterol regulation

Nobel laureate Michael Brown, M.D., describes his quest to understand cholesterol during the 2013 Earl W. Sutherland lecture. (Photo by Susan Urmy)

Cholesterol is a tricky molecule to keep in balance. It’s a building block for the cell membrane and is required for cell growth and survival. But too much cholesterol forms solid crystals that are toxic and deadly.

In last week’s 2013 Earl W. Sutherland lecture, Nobel laureate Michael Brown, M.D., described his four-decade quest to understand cholesterol metabolism and regulation.

Brown and longtime colleague Joseph Goldstein, M.D., were awarded the 1985 Nobel Prize in Physiology or Medicine for their discovery of the low density lipoprotein (LDL) receptor and its role in regulating cholesterol levels in blood and cells.

Brown is the Paul J. Thomas Professor of Molecular Genetics and director of the Jonsson Center for Molecular Genetics at the University of Texas Southwestern Medical School in Dallas.

In more recent studies, Brown and Goldstein have uncovered a family of “master regulators” of lipid synthesis called sterol regulatory element binding proteins (SREBPs). Brown described the pathways and proteins the cell uses to “monitor the cholesterol in the plasma membrane” and then communicate – through SREBPs – to the nucleus that the cell needs more or less cholesterol.

“We’re slowly, slowly inching toward the end of the question that Joe and I set out to study, which is how does the cell control the synthesis of the lipids in its plasma membranes,” Brown noted.

Brown said he was especially honored to be presenting a lecture named for Earl W. Sutherland.

“Earl Sutherland is indeed a giant in the field that Joe Goldstein and I have studied our entire career, which is at the interface between biochemistry and physiology – using reductionist science to discover new molecules and then expanding into physiology to figure out what those molecules do. It’s a noble tradition, and Earl Sutherland was a founder of the whole concept.”

The Department of Molecular Physiology and Biophysics sponsored Brown’s lecture. For a complete schedule of the Flexner Discovery Lecture series and archived video of previous lectures, go to