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Research
Interest:
My research has been focused on understanding the pathogenic mechanisms of neurodegenerative diseases, an assortment of central nervous system disorders characterized by progressive deterioration of neurons. These devastated disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), are essentially no cure at present, and our major challenge is to understand the molecular bases of underlying disease pathogenesis. While both AD and PD are largely sporadic incidences, small numbers of familiar forms have provided an opportunity to reveal molecular mechanisms of the diseases. Our strategy is to utilize those identified genetic factors to develop disease models that could recapitulate some key pathological or phenotypic features observed in patients. By using both genetic and biochemical approaches, we anticipate to uncovering the molecular and cellular mechanisms that crucial for disease development.
We have obtained Drosophila models for HD and polyglutamine disorders, PD, and AD. Fruit fly has been advanced in developmental research for its versatile molecular and genetic tools; and these advantages have also been adopted for brain research ranged from the studies of sensory systems, human neurological diseases, to learning and memory. Our current efforts are focusing on the creation of a Drosophila model for Parkinson's disease, in particular the role of human mutant parkin linked familiar form of PD. Our work also has bearing on a group of related disorders also associated with tau pathology, including frontotemporal dementia, corticobasal degeneration, and progressive supranuclear palsy. In particular, we are interested in the role of kinases in development of tau pathology, and we have performed genetic screens to isolate novel modifiers of tauopathy. Our researches also extend to Huntington's disease and other polyglutaminopathies; specifically, we are most interested in how protein quality control in cells could impact on the progression of polyglutamine disorders. Ultimately, our goal is to identify new therapeutic targets for PD, AD, HD, and tauopathies; these may then be further validated in mammalian systems, using industry collaborations to identify small molecule drugs, or, alternatively, developed as gene therapy.
Honors:
John J. Wasmuth Postdoctoral Fellowship, Hereditary Disease Foundation, 2002-2005.
97年度國立清華大學生命科學院新進教師研究獎
Selected Publications:
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Chang YC, Hung WT, Chang YC, Chang HC, Wu CL, Chiang AS, Jackson GR, Sang TK*. (2011) Pathogenic VCP/TER94 alleles are dominant actives and contribute to?neurodegeneration by altering cellular ATP level in a Drosophila IBMPFD model. PLoS Genet 7(2): e1001288.
- Chatterjee S., Sang T.-K., Lawless G.M., Jackson G.R. (2008) Dissociation of Tau Toxicity and Phosphorylation: Role of GSK-3{beta}, MARK, and Cdk5 in a Drosophila Model. Hum Mol Genet. Oct 17. [Epub ahead of print]
- Sang T.-K., Chang H.Y., Lawless G.M., Ratnaparkhi A., Mee L., Ackerson L.C., Maidment N.T., Krantz D.E., Jackson G.R. (2007) A Drosophila model of mutant human parkin-induced toxicity demonstrates selective loss of dopaminergic neurons and dependence on cellular dopamine.
J. Neurosci. 27(5): 981-92.
- Karsten S.L., Sang T.-K ., Gehman L.T., Chatterjee S., Liu J., Lawless G.M., Sengupta S., Berry R.W., Pomakian J., Oh H.S., Schulz C., Wiedau-Pazos M., Vinters H.V., Binder L.I., Geschwind D.H., and Jackson G.R. (2006) A genomic screen for modifiers of tauopathy: Identification of puromycin-sensitive aminopeptidase as an inhibitor of tau-induced neurodegeneration. Neuron. 51(5):549-560.
- Jackson, G. R., Sang, T.-K. and Taylor, J. P. Drosophila Models of Polyglutamine Disorders. Ed.: Wells, R., and Ashizawa, T. (2006) Genetic Instabilities and Neurological Diseases. pp. 587-594. San Diego : Elsevier.
- Sang, T.-K ., and Jackson G.R. (2005) Drosophila models of neurodegenerative disease. NeuroRx. 2(3):438-46. Review.
- Mee L., Honkala H., Kopra O., Vesa J., Finnila S., Visapaa I. , Sang T.-K ., Jackson G.R., Salonen R., Kestila M., and Peltonen L. (2005) Hydrolethalus syndrome is caused by a missense mutation in a novel gene HYLS1. Human Molecular Genetics. 14(11):1475-88.
- Sang, T.-K ., Li, C., Liu, W., Rodriguez, A., Abrams, J.M., Zipursky, S.L., and Jackson, G.R. (2005) Inactivation of Drosophila Apaf-1 Related Killer suppresses formation of polyglutamine aggregates and blocks polyglutamine pathogenesis. Human Molecular Genetics. 14(3): 357-372.
- Jackson , G.R., Wiedau-Pazos, M., Sang, T.-K ., Wagle, N., Brown , C.A. , Massachi, S., and Geschwind, D.H. (2002) Human wild- type tau interacts with wingless pathway components and produces neurofibrillary pathology in Drosophila. Neuron 34: 509-519.
- Sang, T.-K . and Ready, D. F. (2002) Eyes closed, a Drosophila p47 homolog, is essential for photoreceptor morphogenesis. Development 129: 143-154.
- Chang, H.-Y., Sang, T.-K ., Jan, K.-Y., and Chen, C.-T. (1995) The cellular DNA contents and cell volumes of batoids and their systematics. Copeia. 3: 571-576.
- Sang, T.-K. , Chang, H.-Y., Chen, C.-T., and Hui, C.-F. (1994) Population structure of Japanese eel, Anguilla japonica. Mol. Biol. Evol. 11(2): 250-260.
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