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. This can include altered constitutive cellular processes like the ubiquitin-proteasome system (UPS) or the autophagic-lysosomal system (A-LS) which 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 or connections are altered as we identify mechanisms of dysfunction. 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. We are also interested in identifying risks of AD across the globe, focusing on under-represented in research and medicine populations, with a special interest in increasing representation of Asian populations in research and medicine to identify common and distinct genetic and lived experience risk factors for Alzheimer’s disease.

Current Studies:

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 altered neural networks related to sleep/stress impairment. Other research interest includes risk factors for proteostasis dysfunction neurodegeneration and translational relevance (biomarkers, drug development) to AD and related neurodegenerative diseases.

Select Publications

Tam, S, Wear, D, Morrone, CD and Yu, WH. The complexity of extracellular vesicles: bridging the gap between cellular communication and neuropathology. J Neurochem (2024 Apr 22). PMID: 38650384  DOI: 10.1111/jnc.16108 

Simpson, D, Wear, D, Morrone, CD and Yu, WH. A visual approach for inducing dolichoectasia in an animal model to show cerebrovascular dysfunction. JOVE (Journal of Visual Experiments) (May 17, 2024). PMID: 38829135 DOI:10.3791/66792.

Ho, P-C*, Yu, WH*…..Wang, LS. Asian Cohort for Alzheimer's Disease (ACAD) pilot study on genetic and non‐genetic risk factors for Alzheimer's disease among Asian Americans and Canadians. Alzheimer and Dementia (2024) Jan 12; p1-14. DOI: 10.1002/alz.13611 PMID: 38215053 *Equal contribution 

Morrone CD, Raghuraman R, Hussaini SA, Yu WH. Proteostasis failure exacerbates neuronal circuit dysfunction and sleep impairments in Alzheimer's disease.  Mol Neurodegeneration 2023 Apr 21;18(1):27. doi: 10.1186/s13024-023-00617-4. PMID: 37085942.)

CD Morrone, A Tsang, S Giorshev, E Craig and WH Yu. Concurrent behavioral and electrophysiological recordings for in vivo assessment of aging and neurodegeneration. Front Aging Neurosci. 2023 Jan 18;14:952101. doi: 10.3389/fnagi.2022.952101.

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.