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Protein Quality Control and Neurodegeneration
A hallmark of all neurodegenerative diseases is the accumulation of proteins. Protein homeostasis is a critical element of all cells but neuronal function is particularly susceptible to perturbations in this pathway. Autophagic-lysosomal (A-L) function is a critical element in maintaining protein quality control and incomplete activity can lead to the buildup of aberrant proteins or dysfunctional organelles. Alzheimer's and Parkinson's disease are two major neurodegenerative diseases that are associated with incompetent autophagic or lysosomal activity. By assessing how the proteins tau and ╬▒-synuclein can accumulate, as well as how lysosomal dysfunction related to mutations in enzymatic function in cell and animal models, we can increase our understanding of the neurodegenerative process and why proteins accumulate. In addition developing small molecules that modulate autophagic-lysosomal function are essential in reversing the disease pathology.
Dr. Wai Haung (Ho) Yu received his Ph.D. in Pharmacology from the University of Toronto and was a recipient of an Alzheimer Society of Canada Pre-doctoral award, as well Ontario Graduate Student Scholarships and the T.I. Sherman Award in Neuroscience. Following his doctoral training, Dr. Yu went to New York University/Nathan Kline Institute on a Canadian Institutes of Health Research Postdoctoral Fellowship, with subsequent promotions to Clinical Instructor and then Assistant Professor at NYU prior to joining the Department of Pathology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University in 2006.
Dr. Yu's research interests include the role of protein quality control, in particular, autophagic-lysosomal degradation and its relationship to neurodegeneration. This research examines the biological outcomes of protein homeostasis in neurons and the deleterious effects of failed degradation, including aggregation of tau and ╬▒-synuclein in Alzheimer's disease and Parkinsonism. In addition, Dr. Yu's lab is developing novel neuronal assays to identify new modulators of autophagic and lysosomal activity that will hopefully be of clinical benefit. Recent funding support includes NIH, Alzheimer Drug Discovery Fund (ADDF), CurePSP, Alzheimer's Association and the American Health Assistance Foundation. Dr. Yu has also served as reviewer for several funding agencies including the Veteran's Administration, ADDF, Alzheimer's Association, W G Weston Foundation (Canada)) and journals (JBC, PLOS One, J Neurosci, etc).