Stephen H. Tsang

Laslo A. Bito Associate Professor of Ophthalmology Professor of Pathology & Cell Biology

635 West 165th Street, Box 112
New York, NY 10032
Phone: 001-212-342-1189
Email: sht2@cumc.columbia.edu

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Degrees

Ph.D. 1996, Columbia University
M.D. 1988, Columbia University

Research Interests

Engineering Genome and Metabolome in Patient-specific Stem Cells. Retinal degenerative diseases, including retinitis pigmentosa (RP) and non-exudative (“dry”) age-related macular degeneration (referred to here as simply “AMD”), affect more than 9 million Americans; this number is expected to more than double by 2020. These are devastating diseases that inevitably leave patients with significant and irreversible vision loss. Retinal degenerative diseases represent the best model for studying and developing therapies for neurodegeneration because the retina is highly and uniquely accessible to invasive and noninvasive manipulations and imaging; noninvasive imaging, in particular, is critical for phenotyping/diagnostics and monitoring disease progression (e.g., assessing therapeutic efficacy).
 
While light-adapted normal rods have a highly anabolic and anaerobic (high lactate) metabolism similar to the Warburg effect observed in stem cells, dark-adapted rods have aerobic (low lactate), high-ATP metabolism similar to neuronal cells. To translate this dark-adaptation therapy to humans (who would rightly reject being maintained in darkness), the PI is  developing  “genetic sunglasses” to promote a constant dark-adapted metabolic state in rods while maintaining a normal light-dark circadian environment.
 
Studies in the PI’s laboratory are tackling the problem of photoreceptor neuronal degeneration by pursuing investigations in three areas, two of which include mouse models: probing the role of phosphodiesterase (PDE) signaling in retinal degeneration, developing stem cell-based therapies for retinal degeneration, and correlating the genotypes of various human photoreceptor cell degenerations with the phenotypes revealed in fundus autofluorescence (AF) images.  Since 1992, the PI has been culturing embryonic stem cells and has used them to create the first gene-targeted model for a recessive form of RP.  In addition, he has rescued vision in mouse models of RP using gene therapy and stem cells. For cell therapy, the PI’s laboratory was the first to restore retinal function in mice using human induced pluripotent stem (iPS) cells – and to do so without inducing tumor formation. These achievements depended on novel preclinical models generated in the PI laboratory, including gene-targeted humanized mice and human iPS-derived cells – both with patient-specific mutations. PI’s team group also developed the first patient-specific model for an age-related macular degeneration.
 
Apart from the laboratory’s overall goal, pushing forward the frontiers of regenerative medicine, another major mission is to help students to develop their full potential and become outstanding scientists. In the past, Dr. Tsang’s laboratory has tailored projects to build on and expand students’ and fellows’ existing research skills.

Recent Publications (Pubmed)

Koch SF, Tsai YT, Duong JK, Wu WH, Hsu CW, Wu WP, Bonet-Ponce L, Lin CS, TSANG SH.  Halting progressive neurodegeneration in advanced retinitis pigmentosa. 2015. Journal of Clinical Investigation. 2015 Sep;125(9):3704-13. doi: 10.1172/JCI82462. Epub 2015 Aug 24. PMID:26301813. Cited 5 times.

Wu WH, Tsai YT, Justus S, Lee TT, Zhang L, Lin CS, Bassuk AG, Mahajan VB, TSANG SH. CRISPR Repair Reveals Causative Mutation in a Preclinical Model of Retinitis Pigmentosa. Molecular Therapy 2016 Aug;24(8):1388-94. doi: 10.1038/mt.2016.107. Epub 2016 May 20. PMID:27203441. New publication (May 20), no citations yet.

Lijuan Zhang, Jianhai Du, Sally Justus, Chun-Wei Hsu, Luis Bonet-Ponce, Wen-Hsuan Wu, Yi-Ting Tsai , Wei-Pu Wu, Yading Jia, Jimmy K. Duong, Vinit B. Mahajan, Chyuan-Sheng Lin,  Shuang Wang, James B. Hurley, STEPHEN H TSANG.   Reprogramming Sirtuin 6 attenuates retinal degeneration  Journal of Clinical Investigation. Nov 15, 2016, no citations yet.

Tsang S.H., Gouras P., Yamashita C.K., Fisher J., Farber D.B., and Goff SP (1996). Retinal Degeneration in Mice Lacking the γ subunit of cGMP phosphodiesterase. Science 272: 1026-1029.

Tsang S.H., Burns, M. E., Calvert, P. D., Gouras, P., Baylor, D. A., Goff, S. P., and Arshavsky, V. Y. (1998). Role of the Target Enzyme in Deactivation of Photoreceptor G Protein in Vivo. Science. 282, 117-21.


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