Robert Mahley, MD, PhD
President Emeritus and Senior Investigator, Gladstone Institute of Neurological Disease

Other Professional Titles

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

Phone

(415) 734-2061

Fax

(415) 355-0820

Assistant

Charlotte Pfeiffer
(415) 734-2062

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.

Lab Focus

How does apoE4 contribute to the pathogenesis of Alzheimer's disease, traumatic brain injury, and other neurodegenerative disorders? This includes understanding how the structure of apoE4 causes detrimental effects in neurons, determining how apoE4 impairs mitochondrial function, and determining 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?

Achievements

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

Affiliations

  • American Heart Association (Fellow)
  • California Academy of Medicine
  • 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
  • National Academy of Sciences
  • American Academy of Arts & Sciences

Professional titles

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

Education

1963
BS
  • Maryville College
1968
PhD
  • Vanderbilt University
1970
MD
  • Vanderbilt University

Honors and Awards

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