Neat!

Weihong Song

Professor, Department of Psychiatry, Faculty of Medicine
Fellow of Canadian Academy of Health Sciences
Senior Advisor to the President on China
Canada Research Chair (Tier 1) in Alzheimer's Disease
Jack Brown and Family Professor
Associate Director, Institute of Mental Health
Director, Division of Basic Neuroscience
Director, Townsend Family Laboratories

Email: weih...@mail.ubc.ca
Phone: (Office) 604 822-8019 (lab) (604) 822-7332, 822-7383, 822-7335
Fax: (604) 822-7756 Web pages: Home page

 

Education

  • Dr. Weihong Song was trained as a clinical psychiatrist and molecular neuroscientist. He received his medical degree from Chongqing Medical University in 1983. After completing psychiatry residency and research program with a Master of Medicine degree at West China University of Medical Sciences in 1986, he then worked as a clinical psychiatrist and a Lecturer of Psychiatry at West China University of Medical Sciences. Dr. Song received a MSc in psychobiology and behavioral genetics from Purdue University in 1993 and a PhD in medical neurobiology and molecular genetics from the Department of Psychiatry at Indiana University School of Medicine. He did his postdoctoral training in the Department of Neurology at Harvard Medical School and the Children's Hospital (1996-99), and worked as an Instructor at Harvard Medical School (1999-2001).

  • Dr. Song is recognized internationally as one of the world's leading researchers on Alzheimer's Disease. He is the Tier 1 Canada Research Chair in Alzheimer's disease and a Full Professor with tenure at the UBC Department of Psychiatry. He holds the Directorship of Townsend Family Laboratories and serves as the Special Advisor to the President on China at UBC. His lab has made major contribution to the understanding on how BACE1 and ?-secretase regulate APP processing and their role in Alzheimer pathogenesis and drug development. His recent work also defined the molecular pathways contributing to AD pathogenesis in Down Syndrome. He has served on numerous international grant review panels and journal's editorial boards. For his contribution in forging crucial Canada-China collaborations on research and education, he received the 2011 "Friendship Award", China's highest honor for foreign experts. Dr. Song was elected to Fellowship in the Canadian Academy of Health Sciences (CAHS) in 2012, one of the highest honors for members of the Canadian health sciences community.

Keywords

  • Alzheimer's Disease

  • Down Syndrome


Research Interests

My laboratory focuses on the molecular and cellular mechanism of Alzheimer's Disease (AD) pathogenesis.

Alzheimer's disease is the most common neurodegenerative disorder leading to dementia. It accounts for two-thirds of all cases of dementia and its prevalence increases with age. AD affects about 10% of the population over the age of 65.

Deposition of Aβ in the brain is a central pathological feature of AD. Aβ is derived from APP, a type 1 transmembrane protein. Recent molecular genetic studies have shown that four genes confer susceptibility to AD: APP gene on chromosome 21; Apo E gene on chromosome 19; Presenilin 1 (PS1) on chromosome 14; and Presenilin 2 (PS2) on chromosome 1. Autosomal dominant inheritance of AD can arise from mutations of APP or PS1 and PS2. These mutations alter the processing of APP giving rise to increased production of Aβ, or a 42 amino acid form of Aβ with a high propensity for plaque formation, implicating a role for altered APP processing in the pathogenesis of familial AD.

APP undergoes a complex set of proteolytic processing by three different enzymes: α, β and γ-secretase. In normal condition, a majority of APP is cleaved by α-secretase within the Aβ domain to generate secreted form of APP (sAPPα) and a smaller 83-residue C-terminal fragment (C83 or CTF&aplha;), and it precludes Aβ generation. Aβ is generated from APP by β-secretase (BACE1) and γ-secretase. APP is cleaved by BACE1 to generate a secreted form of APP (sAPPβ) and a 99-residue membrane-associated fragment (C99). C99 is the substrate of γ-secretase and intramembrane cleavage at the γ site generates Aβ and CTF? fragments.

Using knockout and transgenic models, we have demonstrated that presenilins are absolutely required for β-secretase cleavage of APP to generate Aβ and intramembrane cleavage of Notch to generate NICD. Our lab recently found that SP1 playes an important role in BACE1 gene transcription, and BACE1 is degraded by ubiquitin- proteasome pathway. My laboratory is currently working on projects to further define the role of presenilins and BACE, transcriptional regulation and Notch signal transduction in neurodegeneration. Another research area of laboratory is the molecular genetics of mental disorders.


Selected Publications

Zhang S, Wang Z, Cai F, Zhang M, Wu Y, Zhang J, Song W (2017). BACE1 cleavage site selection critical for amyloidogenesis and Alzheimer's pathogenesis. Journal of Neuroscience, 37(29), 6915-6925.

Zhang Y, Song W. (2017). Islet Amyloid Polypeptide: Another Key Molecule in Alzheimer’s Pathogenesis? Progress in Neurobiology, 153, 100-120.

Zeng J, Chen L, Wang Z, Chen Q, Fan Z, Jiang H, Wu Y, Ren L, Chen J, Li T, Song W. (2017). Marginal vitamin A deficiency facilitates Alzheimer’s pathogenesis. Acta Neuropathologica, 133(6), 967-982.

Wang Z, Sadovnick AD, Traboulsee AL, Ross JP, Bernales CQ, Encarnacion M, Yee IM, de Lemos M, Greenwood T, Lee JD, Wright G, Ross CJ, Zhang S, Song W, Vilariño-Güell C (2016). Nuclear receptor NR1H3 in familial multiple sclerosis. Neuron 90(5), 948-954.

Wu, Y., Zhang, S., Xu, Q., Zou, H., Zhou, W., Cai, F., Li, T. and Song, W. (2016). Regulation of global gene expression and cell proliferation by APP. Scientific Reports 6, 22460.

Zhang X, Wu Y, Duan X, Chen W, Zou H, Zhang M, Zhang S, Cai F, Song W (2015). Upregulation of SET Expression by BACE1 and its Implications in Down Syndrome. Molecular Neurobiology, 51(2), 781-790.

Dong, Z., Han, H., Li, H., Bai, Y., Wang, W., Tu, M., Peng, Y., Zhou, L., He, W., Wu, X., Tan, T., Liu, M., Wu, X., Zhou, W., Jin, W., Zhang, S., Sacktor, T.C., Li, T., Song, W. and Wang, Y.T. (2015). Activity-dependent AMPAR endocytosis is a critical process for LTP decay and memory loss. Journal of Clinical Investigation, 125(1). 234-247.

Wu, Y., Deng, Y., Zhang, S., Luo, Y., Cai, F., Zhang, Z., Zhou, W., Li, T., and Song, W. (2015). Amyloid-β precursor protein facilitates the regulator of calcineurin 1-mediated apoptosis by downregulating proteasome subunit α type-5 and proteasome subunit β type-7. Neurobiology of Aging, 36(1), 169-177.

Zhang, M., Cai, F., Zhang, Sh., Zhang, S., and Song, W. (2014). Overexpression of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) delays Alzheimer’s progression in vivo. Scientific Reports, 4, 7298.

Zhang, S., Zis, O., Ly, P.T.T., Wu, Y., Zhang, S., Zhang, M., Cai, F., Bucala, R., Shyu, W-C., and Song, W. (2014). Downregulation of MIF by NF?B under hypoxia accelerated neuronal loss during stroke. The FASEB Journal, 28, 4394-4407.

Shi, Y., Li, J., Chen, C., Gong, M., Chen, Y., Liu, Y., Chen, J., Li, T., and Song, W. (2014). 5-mehtyltetrahydrofolate rescues alcohol-induced neural crest cell migration abnormalities. Molecular Brain, 7, 67.

Sun, X., Wu, Y., Herculano, B., and Song, W. (2014). RCAN1 overexpression exacerbates calcium overloading-induced neuronal apoptosis. PloS ONE, 9, e95471.

Ly PT, Wu Y, Zou H, Wang R, Zhou W, Kinoshita A, Zhang M, Yang Y, Cai F, Woodgett J, Song W. (2013). Inhibition of GSK3beta-mediated BACE1 expression reduces Alzheimer-associated phenotypes. Journal of Clinical Investigation, 123, 224-235.

Wu Y., and Song W (2013). Regulation of RCAN1 translation and its role in oxidative stress-induced apoptosis. The FASEB Journal, 27, 208-221.

Yang, Y., Wu, Y., Zhang, S., and Song, W. (2013). High glucose promotes A? production by inhibiting APP degradation. PloS One, 8, e69824.

Deng, Y., Wang, Z., Wang, R., Zhang, X., Zhang, S., Wu, Y., Staufenbiel, M., Cai, F., and Song, W. (2013). A? Glu11 is the major ?-secretase site of BACE1 and shifting the cleavage site to A? Asp1 contributes to Alzheimer pathogenesis. European Journal of Neuroscience, 37, 1962-1969.

Liu, X., Wang, Z., Wu, Y., Wang, J., and Song, W. (2013). BACE2 degradation mediated by the macroautophagy-lysosome pathway. European Journal of Neuroscience, 37, 1970-1977.

Zhang M, Deng Y, Luo Y, Zhang S, Zou H, Cai F, Wada K, Song W. (2012). Control of BACE1 degradation and APP processing by ubiquity carboxyl-terminal hydrolyses. Journal of Neurochemistry, 120, 1129-1138.

Xu Q, Guo H, Zhang X, Tang B, Cai F, Zhou W, Song W.(2012). Hypoxia regulation of ATP13A2 (PARK9) gene transcription. Journal of Neurochemistry, 122, 251-259.

Chen CH, Zhou W, Liu S, Deng Y, Cai F, Tone M, Tone Y, Song W (2012). Increased NFkappaB signaling upregulates BACE1 expression and its therapeutic potential in Alzheimer's Disease.International Journal of Neuropsychopharmacology 15, 77-90.

Liu S, Zhang S, Bromley-Brits K, Cai F, Zhou W, Xia K, Mittelholtz J, Song W (2011). Transcriptional regulation of TMP21 by NFAT. Molecular Neurodegeneration 6, 21.

Sun X, Wu Y, Chen B, Zhang Z, Zhou W, Tong Y, Yuan J, Xia K, Gronemeyer H, Flavell RA, Song W (2011). Regulator of calcineurin 1 (RCAN1) facilitates neuronal apoptosis through caspase 3 activation. Journal of Biological Chemistry 286, 9049-9062.

Wang L, Zis O, Ma G, Shan S, Zhang X, Wang S, Dai C, Zhao J, Lin Q, Lin S, Song W (2009). Upregulation of macrophage migration inhibitory factor (MIF) gene expression in stroke. Stroke 40, 973-976.

Qing H, He G, Ly PTT, Fox CJ, Staufenbiel M, Cai F, Zhang Z, Wei S, Sun X, Chen CH, Zhou W, Wang K, Song W (2008). Valproic acid inhibits Abeta production, neuritic plaque formation and behavioral deficits in Alzheimer's disease mouse models. The Journal of Experimental Medicine 205, 2781-2789.

Liu S, Bromley-Brits K, Kun X, Mittelholtz J, Wang R, Song W (2008). TMP21 degradation is mediated by the ubiquitin proteasome pathway. European Journal of Neuroscience 28, 1980-1988.

He G, Qing H, Ton Y, Cai F, Ishiura S, Song W (2007). Degradation of Nicastrin involves both proteasome and lysosome. Journal of Neurochemistry 101, 982-992.

Sun X, He G, Qing H, Zhou W, Dobie F, Cai F, Staufenbiel M, Huang LE, Song W (2006). Hypoxia facilitates Alzheimer's disease pathogenesis by upregulating BACE1 gene expression. Proceedings of National Academy of Sciences of the USA 103, 18727-18732.

Sun X, He G, Song W (2006). BACE2, as a novel APP theta-secretase, is not responsible for the pathogenesis of Alzheimer's disease in Down syndrome. The FASEB Journal 20(9):1369-1376.

Sun X, Tong Y, Qing, H. Chen C-H, Song W (2006). Increased BACE1 maturation contributes to the pathogenesis of Alzheimer's disease in Down syndrome. The FASEB Journal 20, 1361-1368.

Zhou W, Song W (2006). Leaky scanning and reinitiation regulate BACE1 gene expression. Molecular and Cellular Biology 26(9): 3353-64.

Li Y, Zhou W, Tong Y, He G, Song W (2006). Control of APP processing and Abeta generation level by BACE1 enzymatic activity and transcription. The FASEB Journal 20(2):285-92.

Sun X, Wang Y, Qing H, Christensen MA, Liu Y, Zhou W, Tong Y, Xiao C, Huang Y, Zhang S, Liu X, Song W (2005). Distinct transcriptional regulation and function of the human BACE2 and BACE1 genes. The FASEB Journal 19(7):739-749.

Tong Y, Zhou W, Fung V, Christensen MA, Qing H, Sun X, Song W (2005). Oxidative stress potentiates BACE1 gene expression and Abeta generation. Journal of Neural Transmission 112(3):455-69.

Christensen MA, Zhou W, Qing H, Lehman A, Philipsen S, Song W (2004). Transcriptional regulation of BACE1, the beta-amyloid precursor protein beta-secretase, by Sp1. Molecular and Cellular Biology 24(2):865-74.

Qing H, Zhou W, Christensen MA, Sun X, Tong Y, Song W (2004). Degradation of BACE by the ubiquitin-proteasome pathway. The FASEB Journal 18(13):1571-3.

Xu J, Kao SY, Lee FJ, Song W, Jin LW, Yankner BA (2002). Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nature Medicine 8(6):600-6.

Zhang Z, Nadeau P, Song W, Yuan M, Donoviel D, Bernstein A, Yankner BA (2000). Presenilins are required for gamma-secretase cleavage of beta-APP and transmembrane cleavage of Notch-1. Nature Cell Biology 2, 463-465.

Song W, Nadeau P, Yuan M, Yang X, Shen J, Yankner BA (1999). Proteolytic release and nuclear translocation of Notch-1 are induced by presenilin-1 and impaired by pathogenic presenilin-1 mutations. Proceedings of National Academy of Sciences of the USA 96, 6959-6963.

Other

Member of Editorial Board:

Journal of Clinical Investigation
Journal of Neurochemistry
Frontiers in Molecular Neuroscience
Journal of Molecular Neuroscience
Current Alzheimer Research

Job opportunities

We have post-doctoral and doctoral positions available. Please send your CV to Dr. Song. 

 

UBC