Scientific Advisory Board
Robert Mahley M.D., Ph.D.
Bob Mahley is a Senior Investigator and President Emeritus/Founder of the Gladstone Institutes and Professor of Pathology and Medicine at the University of California, San Francisco. As President, he oversaw establishment of Gladstone in 1979 and its growth to three institutes. As president-emeritus since 2010, he continues his research on Alzheimer's disease.
He is well known for research on heart disease, cholesterol metabolism and Alzheimer's disease. His research defined the critical role apolipoprotein E (apoE) in atherosclerosis, and more recently its role in the pathogenesis of neurodegenerative disorders. With his associates he has identified small molecules that "correct" the structure of apoE4 and, thus, prevent the detrimental effects of apoE4 in cells and animal models of Alzheimer's disease. To accelerate the progress on these apoE4 "structure correctors", he cofounded E-Scape Bio, Inc. in 2015.
He is a member of the National Academy of Sciences, the National Academy of Medicine, and the American Academy of Arts & Sciences.
Bob completed MD and PhD degrees and a pathology internship at Vanderbilt University. In 1971, he joined the staff of the National Heart, Lung, and Blood Institute and, in 1975, became head of the Comparative Atherosclerosis and Arterial Metabolism Section. Four years later, he was recruited to create the Gladstone Institutes.
Guojun Bu, Ph.D.
Guojun Bu is a Mary Lowell Leary Professor of Medicine and a Professor of Neuroscience in the Department of Neuroscience at Mayo Clinic Jacksonville, and the Jorge and Leslie Bacardi Associate Director of the Mayo Clinic Center for Regenerative Medicine. He is also an Associate Director for Mayo Clinic Alzheimer's Disease Research Center. Prior to joining Mayo Clinic in 2010, he was a Professor of Cell Biology and Neuroscience at the Washington University School of Medicine in St. Louis. Dr. Bu received his B.S. degree in biology from Beijing Normal University, his Ph.D. degree in biochemistry from Virginia Tech, and completed his postdoctoral training in cell biology at the Washington University School of Medicine.
Dr. Bu is a leader in the field of apoE and apoE receptors, which play critical roles in the pathogenesis of Alzheimer's disease. His primary interest is to understand why APOE4 is a strong genetic risk factor for Alzheimer's disease and how this pathway can be targeted for therapy by studying animal and stem cell-based cellular and organoid models. Dr. Bu has received numerous honors and awards including the Zenith Fellows Award from the Alzheimer's Association, the Established Investigator Award from the American Heart Association, the Investigator of the Year award from the Mayo Clinic, and the MetLife Foundation Award for Medical Research in Alzheimer's disease. Dr. Bu frequently serves in review panels for the National Institutes of Health and is a member of the Scientific Advisory Board of the BrightFocus Foundation. He is the Co-Editor-in-Chief of Molecular Neurodegeneration and an Associate Editor for Science Advances.
Yadong Huang, Ph.D.
Dr. Huang is the director and senior investigator of the Gladstone Center for Translational Advancement at the J. David Gladstone Institutes and professor at the Departments of Neurology and Pathology, University of California, San Francisco (UCSF). Dr. Huang has been studying the pathogenesis of Alzheimer's disease (AD), focusing on the roles of apolipoprotein (apo) E4—the major genetic risk factor for AD—using transgenic and gene-targeted mouse models, mouse primary neurons, and human neurons derived from induced pluripotent stem cells (iPSCs). His lab demonstrated that apoE4 is cleaved by a neuron-specific protease, leading to the generation of neurotoxic fragments that contribute to AD pathogenesis. His lab also showed that expression of apoE4 or its fragments causes age-dependent impairment of GABAergic interneurons in the hippocampus, learning to learning and memory deficits. He has been heavily involved in identifying strategies for treatment or prevention of AD by targeting apoE4, including development of apoE4 structure correctors and protease inhibitors and stem cell therapy. Dr. Huang has published more than one hundred scientific papers in the field of apoE, AD, stem cell research, and drug discovery. He is a co-founder of E-Scape Bio, Inc.
Dennis Selkoe, M.D.
Dennis Selkoe is the Vincent and Stella Coates Professor of Neurologic Diseases at Harvard Medical School and Brigham and Women's Hospital. A graduate of Columbia University and the University of Virginia School of Medicine, he trained at the National Institutes of Health, the Harvard/ Longwood Neurology Program and the Department of Neuroscience, Harvard Medical School (HMS). Selkoe and coworkers isolated the neurofibrillary tangles of Alzheimer's disease (AD) and discovered their unusual insolubility and antigenic relationship to tau. He subsequently conducted extensive research on amyloid b-protein (Aß) and its precursor (APP) and helped formulate a theory of AD causation, the "amyloid hypothesis". In 1992, Selkoe and colleagues discovered that Aß is produced by normal cells throughout life, enabling the dynamic study of Ab generation and screens for Ab inhibitors. The lab showed that mutations in APP and, later, presenilin cause AD by increasing Ab production. Selkoe and his colleague, Michael Wolfe, identified presenilin as g-secretase, an unprecedented intramembrane aspartyl protease that processes APP, Notch and many other proteins in all metazoans. His lab has applied similar approaches to alpha-synuclein, the key misfolded protein of Parkinson's disease.
Selkoe has also focused on the translation of his discoveries on the cause and mechanism of Alzheimer's disease into therapeutic approaches. His many scientific articles in Nature, Science, Neuron and other journals have provided the underpinnings of numerous disease-modifying trials currently underway. Dr. Selkoe was the principal founding scientist of Athena Neurosciences, later part of Elan Pharmaceuticals. With HMS Dean Joseph P. Martin, he founded the Harvard NeuroDiscovery Center in 2001. He has received many honors, including the A.H. Heineken Prize for Medicine, the Mathilde Solowey Award in the Neurosciences (NIH), the Potamkin Prize (American Academy of Neurology), the Pioneer Award and Lifetime Achievement Award, Alzheimer's Association, the George C. Cotzias Lecture of the American Academy of Neurology and the Ulysses Medal of University College Dublin. He is a Fellow of the American Association for the Advancement of Science and the American Academy of Neurology and a member of the National Academy of Medicine. He is now a founding director of Prothena Biosciences.