Profile of Robert W. Mahley

Heart disease and the church were two forces that shaped the teenage years of cardiovascular biologist Robert W. Mahley. The first, in the form of a massive heart attack, stole his 37-year-old father; the second provided support through a community of men in his congregation who took the 13-year-old boy under its wing. Originally drawn to become a Presbyterian minister, Mahley instead found a stronger calling in the deep beauty of biology. “I don’t remember actually thinking, ‘I’m going to become a heart disease doctor and cure my father’s illness,’ but to be a 13-year-old and lose your father—that most likely planted something pretty deep in my subconscious,” Mahley says. “When I started working on lipids in the early 1960s, I was immediately attracted.”

Not long after he began studying animals fed high-cholesterol diets, Mahley found an intriguing protein in high concentrations in lipoproteins. Eventually known as apolipoprotein (apo) E, this 34,000-kDa glycoprotein was found to play a critical role in cardiovascular disease as well as neurobiology. Mahley has spent nearly 40 years studying the structure and function of apoE, leading to an understanding of the isoforms associated with type III hyperlipoproteinemia and Alzheimer’s disease. His Inaugural Article in this issue of PNAS (1) discusses the future of therapeutics for apoE in neurobiology.

Elected to the National Academy of Sciences in 2000 and the Institute of Medicine in 2001, Mahley was the first M.D./Ph.D. student to formally graduate from Vanderbilt University School of Medicine (Nashville, TN). In 1979, he was recruited to become a founding director of the Gladstone Institute of Cardiovascular Disease in San Francisco, where he remains today as both a senior investigator and as president of the J. David Gladstone Institutes, newly housed in an architecturally acclaimed building overlooking the San Francisco Bay.