Alzheimer's Disease Research
Wai Haung (Ho) Yu, Ph.D.
Columbia University Medical Center, Taub Institute for Alzheimer’s Disease Research
New York, NY, United States
Title: Tau Homeostasis Via Proteasomal and Autophagic Activity
Non-Technical Title: How Brain Cells Take Away Garbage, and Is It Possible to Improve This Function?
Acknowledgements: This grant is made possible by a generous bequest from the Estate of Donald A. Reitzer.
Duration: July 1, 2012 - June 30, 2015
Award Type: Standard
Award Amount: $300,000
Dr. Wai Haung Yu and colleagues will determine how the natural protein recycling systems, called the ubiquitin-proteasome (UPS) and autophagic-lysosome system (A-LS), act in concert to maintain healthy levels and quality of proteins. In Alzheimer's disease (AD), protein clumping is a hallmark that is often accompanied by failure of UPS and A-LS, suggesting that these two recycling pathways are important for disease prevention. Along with improving the understanding of these two mechanisms, these researchers will test drug candidates for enhancement of UPS and A-LS function in reducing tau clumping and for restoring long-lived UPS and A-LS protein recycling activity.
Dr. Wai Haung Yu and colleagues are exploring how proteins—the building blocks of all cells—are recycled in brain cells, and what happens when there is a malfunction in the machinery to break down and recycle redundant and toxic proteins. One of the main hallmarks of Alzheimer's disease is the presence of aggregated protein deposits, including one set of deposits caused by a protein called tau. This can be a result of proteins that are not degraded by systems called ubiquitin-proteasome (UPS) or autophagic-lysosomal (A-LS), which are two of the primary ways cells get rid of and recycle their junk. The UPS and A-LS pathways are important for maintaining quality control in a cell, and when they fail, the cell begins to accumulate junk proteins, which can be harmful to the cell and can negatively affect its operations and/or lead to disease. Although these two pathways are vital to survival, the connection between them is not well understood in diseases like AD. Moreover, this work will also determine whether scientists can protect and reverse the disease process by improving UPS and A-LS function to reduce the buildup of proteins like tau and preserve healthy brain cell function.
Haung (Ho) Yu received three degrees from the University of Toronto: B.Sc. (Honours, Toxicology and Ecology), M.Sc. (Pharmacology), and Ph.D. (Pharmacology). Following his Ph.D., he received a fellowship from the Canadian Institutes of Health Research with a placement at Nathan Kline Institute/New York University. Yu was promoted to faculty level positions at NYU (Psychiatry) and continued there until he moved to Columbia University (Taub Institute, Department of Pathology and Cell Biology). Yu’s research focuses on protein quality control with an emphasis on tauopathy and synucleinopathy in Alzheimer’s and Parkinson’s disease. His lab is also involved in early-stage drug development with strategies to enhance protein clearance through the modulation of the protein quality control centers (autophagy and proteasomes).