Robert Mahley, MD, PhD

Robert Mahley is a senior investigator, president emeritus, and founder of Gladstone Institutes. He is a professor of pathology and medicine at UC San Francisco. Mahley earned his BS from Maryville College and his MD and PhD from Vanderbilt University. In 1971, he joined the staff of the National Heart, Lung, and Blood Institute (NHLBI) and, in 1975, became head of the Comparative Atherosclerosis and Arterial Metabolism Section in NHLBI’s Laboratory of Experimental Atherosclerosis. Mahley was recruited 4 years later to create Gladstone Institutes. He is a member of the National Academy of Sciences, the National Academy of Medicine, and the American Academy of Arts and Sciences.

As Gladstone’s president, Mahley oversaw the organization’s establishment and growth, including the creation of the Gladstone Institute of Cardiovascular Disease, Institute of Virology and Immunology, and Institute of Neurological Disease. In 2006, he developed the Gladstone Center for Translational Research to facilitate the movement of Gladstone’s basic research into therapeutic development. Mahley’s research defined the critical role of apolipoprotein (apo) E in cholesterol homeostasis, atherosclerosis, and the nervous system. These findings laid the groundwork for the explosion of research linking apoE4—a variant of apoE—to the pathogenesis of Alzheimer’s disease and other neurodegenerative disorders.

His current research focuses on elucidating the cellular and molecular mechanisms whereby apoE4 results in neurodegenerative disorders, and on approaches for altering the detrimental effects of apoE4 in neurons. He has identified a series of small molecules that convert the abnormal structure of apoE4 to a much less toxic structure. In addition, his lab is focusing on how apoE4 expression in neurons impairs cellular metabolism and mitochondrial function.