Robert W. Mahley, MD, PhD

President Emeritus

Senior Investigator

Phone: (415) 734-2061
Phone: (415) 734-2000
Fax: (415) 355-0820
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Other Professional Titles

Professor, Pathology and Medicine, University of California, San Francisco

Executive Assistant

Sylvia Richmond
(415) 734-2062
srichmond@gladstone.ucsf.edu

More about Dr. Mahley

As Gladstone’s President, Dr. Mahley oversaw the organization’s establishment and growth to include three institutes. In 2006, he developed the Gladstone Center for Translational Research to facilitate the movement of some aspects of Gladstone’s basic research into developmental targets. In 2010, after
 30 years as president, he stepped down to more actively pursue his research.

Dr. Mahley is an internationally known expert on heart disease, cholesterol metabolism and, more recently, Alzheimer’s disease. He studies plasma lipoproteins and particularly apolipoprotein E (apoE), the major genetic risk factor for Alzheimer’s disease. His seminal research has defined apoE’s critical role in cholesterol homeostasis and atherosclerosis. He has also made fundamental contributions to understanding the role of apoE in the nervous system, specifically in nerve injury and regeneration and in the remodeling of neurites on neuronal cells. These findings laid the groundwork for the explosion of research linking apoE4—a variant of apoE—to the pathogenesis of Alzheimer’s and neurodegeneration.

In 1971, Dr. Mahley joined the staff of the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health, and in 1975 became head of the Comparative Atherosclerosis and Arterial Metabolism Section in NHLBI’s Laboratory of Experimental Atherosclerosis. Four years later, he was recruited to create the Gladstone Institutes. Dr. Mahley is a member of many scientific and professional societies, including the American Heart Association, the American Society for Biochemistry and Molecular Biology, the American Society for Clinical Investigation, the Association of American Physicians, the American Association for the Advancement of Science and the Society for Neuroscience. In addition, he serves on the editorial boards of several scientific journals.

Dr. Mahley is a member of the National Academy of Sciences, the Institute of Medicine and the American Academy of Arts & Sciences. He recently received the Builders of Science Award from Research!America for his leadership as Gladstone’s founding director and president, guiding its growth to become one of the world’s foremost independent research institutes.

After earning a bachelor’s degree from Maryville College, Maryville, Tenn., in 1963, Dr. Mahley completed both an MD and a PhD at Vanderbilt University in 1970. The following year he did a pathology internship at Vanderbilt.

More scientific details, please

Other Professional Titles

Professor, Pathology and Medicine, University of California, San Francisco

Executive Assistant

Sylvia Richmond
(415) 734-2062
srichmond@gladstone.ucsf.edu

Areas of Investigation

Our laboratory focuses on the structure and function of apolipoprotein (apo) E, including its critical role in cholesterol homeostasis, atherosclerosis and neurodegenerative disorders such as Alzheimer's disease and traumatic brain injury. Several areas are under investigation, including:

  • ApoE as a major causative factor and therapeutic target in Alzheimer's disease and other neurodegenerative disorders; small-molecule structure correctors to convert apoE4 to apoE3 and reverse the detrimental effects of apoE4 on mitochondria and the cytoskeleton; small-molecule protease inhibitors to block the formation of toxic fragments of apoE4;
  • Plasma lipoprotein metabolism regulation involving apoE and apoB; cholesterol homeostasis modulation by lipoprotein receptors controlling lipoprotein clearance by the liver;
  • Plasma HDL cholesterol (HDL-C) metabolism in the progression of atherosclerosis; the genetic epidemiology of the metabolic syndrome and low HDL-C levels established by the Turkish Heart Study.

Current Lab Focus

  • How does apoE4 contribute to the pathogenesis of Alzheimer's disease, traumatic brain injury, and other neurodegenerative disorders?
    • Understand how the structure of apoE4 causes detrimental effects in neurons;
    • Determine how apoE4 impairs mitochondrial function;
    • Determine how apoE4 toxic fragments are generated.
  • What is the genetic cause of low HDL-C levels in the Turkish population?
  • What is the role of apoE in cholesterol homeostasis and atherosclerosis?

Joined Gladstone

1979

Why Gladstone?

I was asked by the Gladstone trustees to establish the Gladstone Institutes in 1979, as a basic science institute with a focus on human disease and committed to training the next generation of scientists.

Key Achievements

  • Involved in the initial discovery of apoE as a major apolipoprotein regulating lipoprotein metabolism:
    • Induced by fat/cholesterol feeding in atherogenesis.
  • Discovered that apoE is a major ligand for the low density lipoprotein receptor:
    • Mapped the amino acid residues involved in receptor binding;
    • Defined the role of apoE in liver clearance of lipoproteins.
  • Defined the three-dimensional structure of apoE:
    • Identified mutations causing type III hyperlipoproteinemia and how apoE2 modulates hyperlipidemia.
  • Recognized the importance of apoE4 in causing neurodegenerative disorders:
    • Defined how the structure of apoE4 causes detrimental effects in neurons.
  • Designed a therapeutic strategy to correct the structure of apoE4; small-molecule structure correctors identified.
  • Defined the impact of apoE4 on mitochondrial function.

Education

Maryville College (BS), Biology (1963)
Vanderbilt University (PhD), Pathology/Anatomy (1968)
Vanderbilt University (MD) (1970)

Affiliations

American Heart Association, Fellow
California Academy of Medicine, Member
American Society for Biochemistry and Molecular Biology
International Academy of Pathology
American Association for the Advancement of Science, Fellow
Association of American Physicians
American Society for Clinical Investigation
Institute of Medicine, elected 2001
National Academy of Sciences, elected 2000
American Academy of Arts & Sciences, elected 2006 

Awards

  • Elected to the American Academy of Arts and Sciences (2007)
  • Received Honorary Doctor of Medicine Degree from Maryville College (2006)
  • Elected to the California Academy of Medicine (2005)
  • Elected to the Institute of Medicine (2001)
  • Distinguished Alumnus Award, Vanderbilt University (2000)
  • Elected to the National Academy of Sciences (2000)
  • Bordon Award for Basic Medical Research, Vanderbilt University (1970)
  • Heinrich Wieland Prize (1982)
  • George Lyman Duff Memorial Lectureship, American Heart Association (1987)
  • CIBA-GEIGY Award in Biomedical Research (1989)
  • MetLife Award for Medical Research in Alzheimer’s Disease, MetLife Foundation (1994)
  • Honorary Degree of Doctor in Medicine, University of Göteborg, Sweden (1995)
  • National Cholesterol Education Program DeWitt S. Goodman Award for Basic Science Achievement (1995)
  • Distinguished Alumnus Award, Vanderbilt University School of Medicine (2000)
  • Honorary Degree of Doctor in Medicine, Maryville College (2006)
  • Outstanding Achievement Award for Contributing to Atherosclerosis Research, International Symposium on Atherosclerosis (2009)
  • Award for Lifetime Achievement in Mentorship, Gladstone Postdoctoral Fellows (2009)
  • Builders of Science Award, Research!America (2010)
  • Salute to Excellence Award, American Liver Foundation (2011)
  • Distinguished Scientist Award, American Heart Association (2011)
  • 24th Annual Robert J. and Claire Pasarow Foundation Award in Cardiovascular Disease (2012)
Syndicate publications

Featured Publications

Robert W. Mahley, MD, PhDHodoglugil U, Mahley RW. Turkish Population Structure and Genetic Ancestry Reveal Relatedness among Eurasian Populations. Ann Hum Genet. 2012 Mar; 76(2):128-41. View in: PubMed
Robert W. Mahley, MD, PhDChen HK, Liu Z, Meyer-Franke A, Brodbeck J, Miranda RD, McGuire JG, Pleiss MA, Ji ZS, Balestra ME, Walker DW, Xu Q, Jeong DE, Budamagunta MS, Voss JC, Freedman SB, Weisgraber KH, Huang Y, Mahley RW. Small molecule structure correctors abolish detrimental effects of apolipoprotein e4 in cultured neurons. J Biol Chem. 2012 Feb 17; 287(8):5253-66. View in: PubMed