Dr. Yang’s primary research interest is to elucidate the pathogenesis of Alzheimer’s disease (AD) at the molecular, cellular, and system levels using human AD brains and cellular and mouse models of AD, and to explore novel therapeutic targets for AD. The research is focused on two integrated aspects:
1) identification of impairments in the autophagic-lysosomal pathway in relation to abnormal degradation and accumulation/storage of proteins and lipids in models of AD; and
2) translational research focusing on remediating the autophagic-lysosomal system in AD models as a potential therapeutic strategy for AD.
Dr. Yang received his medical education at the Shantou University Medical College, his M.S. in Neuroscience from the Sun Yat-Sen University Zhongshan School of Medicine in China, his Ph.D. in Neuroscience from the Australian National University, and postdoctoral training at the University of Western Australia and the University of Toronto’s Center for Research in Neurodegenerative Diseases. He has been with NKI as a Research Scientist since 2001. Dr. Yang was a co-recipient of two research awards from the Ministry of Education and the Ministry of Health, China, and received two Ph.D. scholarships from the Australian National University as well as an Investigator Initiated Research Grant from the Alzheimer’s Association. He has served as a reviewer for a number of international journals including Autophagy, Journal of Neuroscience, Brain, Aging Cell, Human Molecular Genetics, Journal of Neurochemistry, Neurobiology of Aging, Journal of Alzheimer’s Disease, PLoS ONE, Ageing Research Reviews, and Medicinal Research Reviews, and as an Ad Hoc reviewer for grant applications to the Alzheimer’s Association (USA) and the Alzheimer Society of Alberta and the Northwest Territories (Canada).
Lie PPY, Yang DS, Stavrides P, Goulbourne CN, Zheng P, Mohan PS, Cataldo AM, Nixon RA. Post-Golgi carriers, not lysosomes, confer lysosomal properties to pre-degradative organelles in normal and dystrophic axons. Cell Rep. 2021 Apr 27;35(4):109034. doi: 10.1016/j.celrep.2021.109034.
Yang DS, Stavrides P, Kumar A, Jiang Y, Mohan PS, Ohno M, Dobrenis K, Davidson CD, Saito M, Pawlik M, Huo C, Walkley SU, Nixon RA. Cyclodextrin has conflicting actions on autophagy flux in vivo in brains of normal and Alzheimer model mice. Hum Mol Genet. 2017 Mar 1;26(5):843-859. doi: 10.1093/hmg/ddx001.
Yang DS, Stavrides P, Saito M, Kumar A, Rodriguez-Navarro JA, Pawlik M, Huo C, Walkley SU, Saito M, Cuervo AM, Nixon RA. Defective macroautophagic turnover of brain lipids in the TgCRND8 Alzheimer mouse model: prevention by correcting lysosomal proteolytic deficits. Brain. 2014 Dec;137(Pt 12):3300-18. doi: 10.1093/brain/awu278.
Nixon RA, Yang DS. Autophagy failure in Alzheimer's disease--locating the primary defect. Neurobiol Dis. 2011 Jul;43(1):38-45. doi: 10.1016/j.nbd.2011.01.021.
Yang DS, Stavrides P, Mohan PS, Kaushik S, Kumar A, Ohno M, Schmidt SD, Wesson D, Bandyopadhyay U, Jiang Y, Pawlik M, Peterhoff CM, Yang AJ, Wilson DA, St George-Hyslop P, Westaway D, Mathews PM, Levy E, Cuervo AM, Nixon RA. Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer's disease ameliorates amyloid pathologies and memory deficits. Brain. 2011 Jan;134(Pt 1):258-77. doi: 10.1093/brain/awq341.
Yang DS, Kumar A, Stavrides P, Peterson J, Peterhoff CM, Pawlik M, Levy E, Cataldo AM, Nixon RA. Neuronal apoptosis and autophagy cross talk in aging PS/APP mice, a model of Alzheimer's disease. Am J Pathol. 2008 Sep;173(3):665-81. doi: 10.2353/ajpath.2008.071176.
Chishti MA, Yang DS, Janus C, Phinney AL, Horne P, Pearson J, Strome R, Zuker N, Loukides J, French J, Turner S, Lozza G, Grilli M, Kunicki S, Morissette C, Paquette J, Gervais F, Bergeron C, Fraser PE, Carlson GA, George-Hyslop PS, Westaway D. Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695. J Biol Chem. 2001 Jun 15;276(24):21562-70. doi: 10.1074/jbc.M100710200.
Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song YQ, Rogaeva E, Chen F, Kawarai T, Supala A, Levesque L, Yu H, Yang DS, Holmes E, Milman P, Liang Y, Zhang DM, Xu DH, Sato C, Rogaev E, Smith M, Janus C, Zhang Y, Aebersold R, Farrer LS, Sorbi S, Bruni A, Fraser P, St George-Hyslop P. Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing. Nature. 2000 Sep 7;407(6800):48-54. doi: 10.1038/35024009.
Yang DS, Yip CM, Huang TH, Chakrabartty A, Fraser PE. Manipulating the amyloid-beta aggregation pathway with chemical chaperones. J Biol Chem. 1999 Nov 12;274(46):32970-4. doi: 10.1074/jbc.274.46.32970.
Yang DS, Smith JD, Zhou Z, Gandy SE, Martins RN. Characterization of the binding of amyloid-beta peptide to cell culture-derived native apolipoprotein E2, E3, and E4 isoforms and to isoforms from human plasma. J Neurochem. 1997 Feb;68(2):721-5. doi: 10.1046/j.1471-4159.1997.68020721.x.