Wai Haung (Ho) Yu
Loss of protein clearance mechanisms are a key factor in aging and neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. Loss of constitutive cellular processes like the ubiquitin-proteasome system (UPS) or the autophagic-lysosomal system (A-LS) can impact brain health and lead to neuropathological accumulation of canonical proteins associated with disease. This group examines the latter pathway, focusing on how these systems decline and in what brain regions to identify mechanisms of action. Further, as A-LS is a multistep pathway, identifying what part of this system is impacted in aging and disease could lead to therapeutic identification and biomarkers of proteostasis.
Current research is supported by NIH funding on identifying risk factors for Alzheimer’s in Asian populations, large blood vessel disease and Alzheimer’s, proteostasis (autophagy, lysosome, proteasome function), and extracellular vesicles. Other research interest includes risk factors for proteostasis dysfunction neurodegeneration, like sleep deficits, and translational relevance (biomarkers, drug development) to AD and related neurodegenerative diseases.
Chung, KM, Hernandez, N, Sproul, A and WH Yu. Alzheimer’s disease and the autophagic-lysosomal system. Neurosc Lett (2019, Apr); 697(1): 49-58. PMID: 29758300 https://www.sciencedirect.com/science/article/abs/pii/S0304394018303446
Boland, B*, Yu, WH* …. MJ Millan. Clearing neurotoxic proteins in neurodegenerative disorders of aging. Nature Reviews in Drug Discovery (2018, Sep);17(9):660-688. PMID:30116051. *Equal contribution
Friedman, L.G., Qureshi, Y.H. and W. H. Yu. Promoting autophagic clearance: viable therapeutic targets in Alzheimer’s disease. Neurotherapeutics (2015, Jan); 12(1):1-15). PMID: 25421002 PMCID: PMC4322072 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322072/
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. *equal contribution
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.
Nixon, RA, Weigel, J, Kumar, A, Yu, WH, Peterhoff, CM, Cataldo, AM, and Cuervo, AM Autophagy in the neurodegeneration of Alzheimer’s disease. J Neuropath and Experimental Neurol (2005, Feb); 64(2):113-2. PMID: 15751225.