Research Faculty

Address
630 W 168th St
PS12-430
New York NY 10032


Phone: 212-305-8973
Fax: 212-342-0119

why2102@cumc.columbia.edu
Education and Training
Ph.D. University of Toronto
M.Sc. University of Toronto
B.Sc. University of Toronto

Affiliations
Taub Institue
Wai Haung Yu, Ph.D.
Assistant Professor of Pathology & Cell Biology
Research Summary

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 an essential element in maintaining protein, lipid and organellar quality control and incomplete activity can lead to the buildup of aberrant proteins or dysfunctional organelles. Alzheimer's and Parkinson's disease (in particular, carriers of mutations in the glucocerebrosidase gene which is associated with the most common lysosomal storage disorder, Gaucher’s disease) are two major neurodegenerative diseases associated with incompetent autophagic or lysosomal activity. Using cell and in vivo models, we can assess how proteins like tau and α-synuclein accumulate and lead to downstream dysfunction in cognition or motor skills. The goal of this research is to improve our understanding of why proteins accumulate in aging and disease, the consequences, as well as identify possible treatments that target autophagic function by developing small molecules that modulate autophagic flux.
Selected Publications

Friedman, L.G., Qureshi, Y.H. and W. H. Yu. Promoting autophagic clearance: viable therapeutic targets in Alzheimer’s disease. Neurotherapeutics (2014, in press)

Congdon, EE, Wu, JW, Myeku, N, Figueroa, YH, Herman, M, Marinec, PS, Gestwicki, JE, Dickey, CA, Yu, WH and K Duff. Methylthioninium chloride (methylene blue) induces autophagy and attenuates tauopathy in vitro and in vivo. Autophagy (April 1 2012) 8(4):1-14. PMCID: PMC3405840.

Yu, WH and K Duff. Metabolism, Autophagy and Neurodegeneration. (2012) Autophagy of the Nervous System. World Scientific books (eds. CT Chu and Z. Yue).

Lee, J-H, Yu, WH, Kumar, A, Lee, SY, Mohan, PS, Peterhoff, CM, Wolfe, DM, Martinez-Vicente, Massey, AC, Sovak, G, Uchiyama, Y, Westaway, D, Cuervo, AM and RA Nixon. Presenilin 1 (PS1) is required for v-ATPase targeting and autolysosome acidification: PS1 mutations in Alzheimer’s Disease disrupt lysosomal proteolysis and autophagy. Cell (2010) Jun 25; 141(7):1146-58. PMID: 20541250.

Velayati, A, Yu, WH and E. Sidransky. The Role of Glucocerebrosidase Mutations in Parkinson Disease and Lewy Body Disorders. Current Neurology and Neuroscience Reports Vol. 10 Issue 3, 2010. PMCID: PMC3529411.

Yu, WH, Dorado, BJ, Figueroa, HY, Wang, L, Planel, E, Cookson, MR, Clark, LN, and K. Duff. Metabolic state determines the efficacy of macroautophagy clearance of pathological oligomeric αsynuclein. Amer J Path (2009 Aug) 175(2):736-47. PMCID: PMC2716969.

Yu, WH, Cuervo, AM, Kumar, A, Peterhoff, CM, Boland, B, Schmidt, SD, Lee, JH, Mohan, PS, Mercken, M, Farmery, MR, Tjernberg, L, Jiang, Y, Duff, KD, Uchiyama, Y, Näslund, J, Mathews, PM, Cataldo, AM and RA Nixon. Macroautophagy – A novel amyloid-β (Aβ) peptide-generating pathway activated in Alzheimer’s disease. J Cell Biol (2005 Oct 10) 170(7):87-98. PMID: 16203860.

Yu, WH, A Kumar, C Peterhoff, L Shapiro Kulnane, Y Uchiyama, BT Lamb, AM Cuervo and RA Nixon. Autophagic vacuoles are enriched in APP-secretase activities: implications for Aβ peptide overproduction and localization in Alzheimer’s Disease. Intern J Biochem and Cell Biol (2004 Dec) 36(12):2531-40. PMID: 15325590.

Current Projects

Protein quality control in neurodegeneration
Small molecule and drug discovery


Honors and Awards

University of Toronto Open Scholarship for Graduate Studies
Alzheimer Society of Canada Doctoral Fellowship
University of Toronto Open Scholarship for Graduate Studies
Ontario Student Opportunities Training Fellowship
Theodore I. Sherman Graduate Award in Neuroscience
Canadian Institutes of Health Research Postdoctoral Fellowship
Committees , Council, and Professional Society Memberships

President, Greater New York Neuroscience Chapter (2013 Chapter of the Year)
Scientific Advisor, Weston Brain Institute, W. Garfield Weston Foundation,
Alzheimer Drug Discovery Fund (Scientific Review Board)
Department of Veteran’s Affairs, Merit Study Section panelist - Aging & Neurodegenerative Diseases
Keywords

autophagy, proteinopathy tauopathy, lysosome, Alzheimer disease, Parkinson’s disease

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