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.

 

Robert Stroud Ph.D.

Robert M. Stroud is a Professor of Biochemistry and Biophysics at UCSF. He obtained his BA, MA at Cambridge University, and his PhD in J.D. Bernal's laboratory at London University where he developed non-centrosymmetric direct methods to determine structure of the nucleoside antibiotic tubercidin, and vitamins. He was postdoctoral with R. E. Dickerson at Caltech where he determined the first structure of trypsin and trypsinogen showing how the proenzyme is activated to the active protease trypsin. He became associate professor of chemistry at Caltech, and moved to UCSF in 1977 as the founding member of the Macromolecular Structure Group (msg.ucsf.edu). He is a member of the National Academy of Sciences USA, a Fellow of the American Academy of Arts and Sciences, and a Fellow of the Royal Society of Medicine (UK). Stroud's research focuses on the mechanisms of transmembrane transporters, receptors and channels, and on the mechanisms of protein-RNA recognition and chemistry, at the level of atomic structure, mechanisms, inhibition, and structure-based drug discovery.

 

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.

 

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.

 

Tony Wyss-Coray Ph.D.

Tony Wyss-Coray is a professor of Neurology and Neurological Sciences at Stanford University, the Co-Director of the Stanford Alzheimer's Disease Research Center, and a Senior Research Career Scientist at the Palo Alto VA. His lab studies brain aging and neurodegeneration with a focus on age-related cognitive decline and Alzheimer's disease. The Wyss-Coray research team is following up on earlier discoveries which showed circulatory blood factors can modulate brain structure and function and factors from young organisms can rejuvenate old brains. These findings were voted 2nd place Breakthrough of the Year in 2014 by Science Magazine and presented in talks at Global TED, the World Economic Forum, and Google Zeitgeist. Wyss-Coray is the co-founder of Alkahest, a company developing plasma-based therapies to counter age-related diseases such as Alzheimer's. Current studies in his lab focus on the molecular basis of the systemic communication with the brain by employing a combination of genetic, cell biology, and –omics approaches in killifish, mice, and humans and through the development of bio-orthogonal tools for the in vivo labeling of proteins.